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ORTHOPEDICS AND TRAUMATOLOGY (150 journals)                     

Showing 1 - 152 of 152 Journals sorted alphabetically
Acta Orthopaedica     Open Access   (Followers: 32)
Advances in Orthopedics     Open Access   (Followers: 9)
American Journal of Orthodontics and Dentofacial Orthopedics     Hybrid Journal   (Followers: 9)
American Journal of Orthopedics     Partially Free   (Followers: 3)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 9)
Archives of Osteoporosis     Hybrid Journal   (Followers: 1)
Arthritis und Rheuma     Hybrid Journal  
Arthroplasty Today     Open Access   (Followers: 1)
Australasian Musculoskeletal Medicine     Full-text available via subscription   (Followers: 5)
BMC Musculoskeletal Disorders     Open Access   (Followers: 29)
Bone & Joint 360     Full-text available via subscription   (Followers: 19)
Bone Research     Hybrid Journal   (Followers: 2)
Burns & Trauma     Open Access   (Followers: 11)
Cartilage     Hybrid Journal   (Followers: 5)
Case Reports in Orthopedic Research     Open Access  
Case Reports in Orthopedics     Open Access   (Followers: 6)
Chinese Journal of Traumatology     Open Access  
Cleft Palate-Craniofacial Journal     Hybrid Journal   (Followers: 8)
Clinical Medicine Insights : Arthritis and Musculoskeletal Disorders     Open Access   (Followers: 3)
Clinical Orthopaedics and Related Research     Hybrid Journal   (Followers: 78)
Clinical Trials in Orthopedic Disorders     Open Access   (Followers: 1)
Concussion     Open Access  
Craniomaxillofacial Trauma and Reconstruction     Hybrid Journal   (Followers: 1)
Current Orthopaedic Practice     Hybrid Journal   (Followers: 14)
Current Reviews in Musculoskeletal Medicine     Open Access   (Followers: 13)
Der Orthopäde     Hybrid Journal   (Followers: 6)
Die Wirbelsäule     Hybrid Journal  
Duke Orthopedic Journal     Open Access   (Followers: 4)
East African Orthopaedic Journal     Full-text available via subscription  
EFORT Open Reviews     Open Access   (Followers: 1)
Egyptian Orthopaedic Journal     Open Access   (Followers: 1)
EMC - Técnicas Quirúrgicas - Ortopedia y Traumatología     Full-text available via subscription  
EMC - Tecniche Chirurgiche - Chirurgia Ortopedica     Full-text available via subscription  
Ergonomics     Hybrid Journal   (Followers: 23)
European Journal of Orthopaedic Surgery & Traumatology     Hybrid Journal   (Followers: 9)
European Journal of Podiatry / Revista Europea de Podología     Open Access   (Followers: 1)
European Spine Journal     Hybrid Journal   (Followers: 24)
Foot & Ankle International     Hybrid Journal   (Followers: 10)
Foot & Ankle Orthopaedics     Open Access   (Followers: 3)
Gait & Posture     Hybrid Journal   (Followers: 17)
Geriatric Orthopaedic Surgery Rehabilitation     Open Access   (Followers: 5)
Global Spine Journal     Open Access   (Followers: 12)
Hip International     Hybrid Journal  
Indian Journal of Orthopaedics     Open Access   (Followers: 8)
Informationen aus Orthodontie & Kieferorthopädie     Hybrid Journal  
Injury     Hybrid Journal   (Followers: 20)
International Journal of Orthopaedic and Trauma Nursing     Hybrid Journal   (Followers: 11)
International Journal of Orthopaedic Surgery     Open Access   (Followers: 5)
International Journal of Orthopaedics     Open Access   (Followers: 2)
International Journal of Research in Orthopaedics     Open Access  
International Musculoskeletal Medicine     Hybrid Journal   (Followers: 7)
International Orthopaedics     Hybrid Journal   (Followers: 18)
JAAOS : Global Research & Reviews     Open Access   (Followers: 1)
JBJS Journal of Orthopaedics for Physician Assistants     Hybrid Journal  
JBJS Reviews     Full-text available via subscription   (Followers: 11)
JOR Spine     Open Access   (Followers: 3)
Journal de Traumatologie du Sport     Full-text available via subscription   (Followers: 2)
Journal für Mineralstoffwechsel & Muskuloskelettale Erkrankungen     Hybrid Journal  
Journal of Bone and Joint Diseases     Open Access   (Followers: 3)
Journal of Bone and Joint Infection     Open Access   (Followers: 1)
Journal of Brachial Plexus and Peripheral Nerve Injury     Open Access   (Followers: 4)
Journal of Cachexia, Sarcopenia and Muscle     Open Access   (Followers: 2)
Journal of Children's Orthopaedics     Open Access   (Followers: 10)
Journal of Clinical Orthopaedics and Trauma     Hybrid Journal   (Followers: 5)
Journal of Experimental Orthopaedics     Open Access   (Followers: 8)
Journal of Hand Surgery (European Volume)     Hybrid Journal   (Followers: 44)
Journal of Head Trauma Rehabilitation     Hybrid Journal   (Followers: 18)
Journal of Musculoskeletal Research     Hybrid Journal   (Followers: 9)
Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie     Hybrid Journal  
Journal of Orthodontic Science     Open Access   (Followers: 2)
Journal of Orthopaedic & Sports Physical Therapy     Full-text available via subscription   (Followers: 72)
Journal of Orthopaedic Association of South Indian States     Open Access   (Followers: 5)
Journal of Orthopaedic Diseases and Traumatology     Open Access   (Followers: 3)
Journal of Orthopaedic Reports     Full-text available via subscription   (Followers: 12)
Journal of Orthopaedic Research     Hybrid Journal   (Followers: 29)
Journal of Orthopaedic Science     Hybrid Journal   (Followers: 4)
Journal of Orthopaedic Surgery     Open Access   (Followers: 1)
Journal of Orthopaedic Surgery and Research     Open Access   (Followers: 8)
Journal of Orthopaedic Translation     Open Access  
Journal of Orthopaedic Trauma     Hybrid Journal   (Followers: 15)
Journal of Orthopaedics     Full-text available via subscription   (Followers: 3)
Journal of Orthopaedics and Allied Sciences     Open Access   (Followers: 9)
Journal of Orthopaedics and Spine     Open Access   (Followers: 3)
Journal of Orthopaedics and Traumatology     Open Access   (Followers: 16)
Journal of Orthopaedics, Trauma and Rehabilitation     Open Access   (Followers: 6)
Journal of Orthopedics & Rheumatology     Open Access  
Journal of Orthopedics, Traumatology and Rehabilitation     Open Access   (Followers: 6)
Journal of Pediatric Orthopaedics     Hybrid Journal   (Followers: 15)
Journal of Prosthetics and Orthotics     Hybrid Journal   (Followers: 15)
Journal of Scleroderma and Related Disorders     Hybrid Journal  
Journal of the American Academy of Orthopaedic Surgeons     Hybrid Journal   (Followers: 12)
Journal of the American Podiatric Medical Association     Full-text available via subscription   (Followers: 8)
Journal of Traumatic Stress     Hybrid Journal   (Followers: 26)
Knee Surgery, Sports Traumatology, Arthroscopy     Hybrid Journal   (Followers: 27)
Multiple Sclerosis and Related Disorders     Hybrid Journal   (Followers: 9)
Musculoskeletal Care     Hybrid Journal   (Followers: 19)
Musculoskeletal Science and Practice     Hybrid Journal   (Followers: 3)
Nigerian Journal of Orthopaedics and Trauma     Open Access  
North American Spine Society Journal (NASSJ)     Open Access   (Followers: 3)
OA Orthopaedics     Open Access   (Followers: 7)
Obere Extremität     Hybrid Journal   (Followers: 1)
Open Journal of Orthopedics     Open Access   (Followers: 3)
Open Journal of Orthopedics and Rheumatology     Open Access  
Open Journal of Trauma     Open Access  
Open Orthopaedics Journal     Open Access  
Operative Orthopädie und Traumatologie     Hybrid Journal  
Operative Techniques in Orthopaedics     Full-text available via subscription   (Followers: 6)
Orthopädie & Rheuma     Full-text available via subscription  
Orthopädie und Unfallchirurgie up2date     Hybrid Journal  
Orthopaedic Journal of Sports Medicine     Open Access   (Followers: 14)
Orthopaedic Nursing     Hybrid Journal   (Followers: 11)
Orthopaedic Proceedings     Partially Free  
Orthopaedic Surgery     Open Access   (Followers: 1)
Orthopaedics & Traumatology: Surgery & Research     Full-text available via subscription   (Followers: 6)
Orthopaedics and Trauma     Full-text available via subscription   (Followers: 28)
Orthopedic Clinics of North America     Full-text available via subscription   (Followers: 5)
Orthopedic Research and Reviews     Open Access   (Followers: 6)
Orthopedic Reviews     Open Access   (Followers: 7)
Orthopedics     Full-text available via subscription   (Followers: 6)
Orthoplastic Surgery     Open Access  
Osteoarthritis and Cartilage     Full-text available via subscription   (Followers: 20)
Osteoarthritis and Cartilage Open     Open Access  
Osteologie     Hybrid Journal  
Osteoporosis and Sarcopenia     Open Access  
OTA International     Open Access  
Paediatric Orthopaedics and Related Sciences     Open Access   (Followers: 3)
Pain Management in General Practice     Full-text available via subscription   (Followers: 12)
Prosthetics and Orthotics International     Hybrid Journal   (Followers: 9)
Revista Brasileira de Ortopedia     Hybrid Journal  
Revista Chilena de Ortopedia y Traumatología / Chilean Journal of Orthopaedics and Traumatology     Open Access  
Revista Colombiana de Ortopedia y Traumatología     Full-text available via subscription  
Revista Cubana de Ortopedia y Traumatologí­a     Open Access  
Revista de la Asociación Argentina de Ortopedia y Traumatología     Open Access  
Revista Española de Cirugía Ortopédica y Traumatología     Full-text available via subscription   (Followers: 1)
Revista Portuguesa de Ortopedia e Traumatologia     Open Access  
Revue de Chirurgie Orthopédique et Traumatologique     Full-text available via subscription   (Followers: 3)
Romanian Journal of Orthopaedic Surgery and Traumatology     Open Access  
SA Orthopaedic Journal     Open Access   (Followers: 2)
SICOT-J     Open Access   (Followers: 1)
Spine     Hybrid Journal   (Followers: 73)
Spine Journal     Hybrid Journal   (Followers: 26)
Sport-Orthopädie - Sport-Traumatologie - Sports Orthopaedics and Traumatology     Full-text available via subscription   (Followers: 3)
Strategies in Trauma and Limb Reconstruction     Open Access   (Followers: 1)
Techniques in Orthopaedics     Hybrid Journal   (Followers: 6)
Therapeutic Advances in Musculoskeletal Disease     Hybrid Journal   (Followers: 5)
Trauma     Hybrid Journal   (Followers: 5)
Trauma (Travma)     Open Access  
Trauma und Berufskrankheit     Hybrid Journal  
Traumatology     Full-text available via subscription   (Followers: 1)
Traumatology and Orthopedics of Russia     Open Access  
Zeitschrift für Orthopädie und Unfallchirurgie     Hybrid Journal   (Followers: 2)
Ортопедия, травматология и протезирование     Open Access  

           

Similar Journals
Journal Cover
Therapeutic Advances in Musculoskeletal Disease
Journal Prestige (SJR): 1.118
Citation Impact (citeScore): 3
Number of Followers: 5  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1759-720X - ISSN (Online) 1759-7218
Published by Sage Publications Homepage  [1174 journals]
  • Comparable long-term retention rates and effects on bone mineral density
           of denosumab treatment in patients with osteoporosis with or without
           autoimmune inflammatory rheumatic diseases: real-life data

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      Authors: Angelo Fassio, Davide Gatti, Davide Bertelle, Elena Fracassi, Giulia Zanetti, Ombretta Viapiana, Maurizio Rossini, Giovanni Adami
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:To investigate whether concomitant autoimmune inflammatory rheumatic diseases (AIIRDs) represent a risk factor for denosumab discontinuation and to explore other possible predictors.Design:This is a real-life retrospective study conducted at our centre on consecutive patients who started treatment with denosumab from January 2014 to October 2021.Methods:Data on patients’ characteristics, denosumab prescriptions and reason for discontinuation were collected from their medical electronic records. A log-rank test was run to assess differences in the denosumab retention rate between the not AIIRD and AIIRD patients. A backward stepwise logistic regression was used to identify possible predictors of denosumab discontinuation. When available, BMD data of the lumbar spine and total hip were collected.Results:Three hundred and sixty-three patients were included (265 not AIIRD and 98 AIIRD; median follow-up, 44 months). Sixty-nine patients discontinued denosumab at any time point (4 due to patient’s decision, 3 due to medical decision, 62 were lost in follow-up). The log-rank test did not find a statistically significant difference for denosumab persistence between the two subgroups. In the binary logistic regression analysis, only older age at initiation and lower baseline serum 25-hydroxy vitamin D were confirmed as predictors for discontinuation. BMD significantly increased from baseline to the last prescription visit at both the lumbar spine and the total hip, without statistically significant differences in the not AIIRD and AIIRD patients.Conclusion:The present data seem to suggest that AIIRDs do not represent a risk factor for denosumab discontinuation. Furthermore, the presence of AIIRDs does not seem to impair its effectiveness in terms of BMD.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-20T06:07:14Z
      DOI: 10.1177/1759720X221124543
      Issue No: Vol. 14 (2022)
       
  • Plasma calprotectin as a biomarker of ultrasound synovitis in rheumatoid
           arthritis patients receiving IL-6 antagonists or JAK inhibitors

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      Authors: Beatriz Frade-Sosa, Andrés Ponce, José Inciarte-Mundo, Rosa Morlà, Viginia Ruiz-Esquide, Laura Macías, Ana Belen Azuaga, Julio Ramirez, Juan D. Cañete, Jordi Yague, Josep M. Auge, José A. Gomez-Puerta, Raimon Sanmarti
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:To analyse the accuracy of plasma calprotectin in patients with rheumatoid arthritis (RA) receiving monoclonal antibodies against IL-6 receptors (anti-rIL-6) or JAK inhibitors (JAKis) in detecting ultrasound (US) synovitis and compare it with acute phase reactants [high-sensitivity C-reactive protein (hs-CRP) and ESR].Methods:An observational cross-sectional study of RA patients receiving anti-rIL-6 (tocilizumab or sarilumab) or JAKi, (baricitinib or tofacitinib) was made. Plasma calprotectin for the diagnosis of US synovitis [synovial hypertrophy grade (SH) ⩾ 2 plus power Doppler signal (PD) ⩾ 1] was analysed using receiver operating characteristic curves (ROCs). The performance of ESR and hs-CRP was also studied. The three ROC curves were compared to determine which had the highest discriminatory power. Associations between plasma calprotectin and US scores were made using correlation analysis.Results:Sixty-three RA patients were included. Mean plasma calprotectin levels were significantly higher in patients with US synovitis than in those without (0.89 ± 0.85 vs 0.30 ± 0.12 μg/ml; p = 0.0003). A moderate correlation between calprotectin and all US scores (HS score Rho = 0.479; PD score Rho = 0.492; and global score Rho = 0.495) was found. The discriminatory capacity of plasma calprotectin showed an AUC of 0.795 (95% CI: 0.687–0.904). The AUC of hs-CRP and ESR was 0.721 and 0.564, respectively. hs-CRP serum levels showed a low positive correlation with the three US scores (Rho 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-17T12:31:49Z
      DOI: 10.1177/1759720X221114105
      Issue No: Vol. 14 (2022)
       
  • Characterization of missing data patterns and mechanisms in longitudinal
           composite outcome trial in rheumatoid arthritis

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      Authors: Fowzia Ibrahim, Brian D.M. Tom, David L. Scott, Andrew Toby Prevost
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Composite measures, like the Disease Activity Score for 28 joints (DAS28), are key primary outcomes in rheumatoid arthritis (RA) trials. DAS28 combines four different components in a continuous measure. When one or more of these components are missing the overall composite score is also missing at intermediate or trial endpoint assessments.Objectives:This study examined missing data patterns and mechanisms in a longitudinal RA trial to evaluate how best to handle missingness when analysing composite outcomes.Design:The Tumour-Necrosis-Factor Inhibitors against Combination Intensive Therapy (TACIT) trial was an open label, pragmatic randomized multicentre two arm non-inferiority study. Patients were followed up for 12 months, with monthly measurement of the composite outcome and its components. Active RA patients were randomized to conventional disease modifying drugs (cDMARDs) or Tumour Necrosis Factor-α inhibitors (TNFis).Methods:The TACIT trial was used to explore the extent of missing data in the composite outcome, DAS28. Patterns of missing data in components and the composite outcome were examined graphically. Longitudinal multivariable logistic regression analysis assessed missing data mechanisms during follow-up.Results:Two hundred and five patients were randomized: at 12 months 59/205 (29%) had unobserved composite outcome and 146/205 (71%) had an observed DAS28 outcome; however, 34/146 had one or more intermediate assessments missing. We observed mixed missing data patterns, especially for the missing composite outcome due to one component missing rather than patient not attending thier visit. Age and gender predicted missingness components, providing strong evidence the missing observations were unlikely to be Missing Completely at Random (MCAR).Conclusion:Researchers should undertake detailed evaluations of missing data patterns and mechanisms at the final and intermediate time points, whether or not the outcome variable is a composite outcome. In addition, the impact on treatment estimates in patients who only provide data at milestone assessments need to be assessed.Trial Registration ISRCTN Number:37438295
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-17T12:14:55Z
      DOI: 10.1177/1759720X221114103
      Issue No: Vol. 14 (2022)
       
  • High inflammatory burden predicts cardiovascular events in patients with
           axial spondyloarthritis: a long-term follow-up study

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      Authors: Lin-Hong Shi, Steven H. Lam, Ho So, Edmund K. Li, Tena K. Li, Cheuk-Chun Szeto, Lai-Shan Tam
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Axial spondyloarthritis (axSpA) patients are at higher risk of cardiovascular (CV) disease (CVD) than the general population, partly due to consequences of inflammation or its treatment. But relationship between inflammation in axSpA and cardiovascular events (CVE) is unknown.Objectives:To examine whether inflammatory burden over time can predict CVE independent of baseline CV risk factors in axSpA patients.Design:A cohort analysis was performed in patients who had been recruited since January 2001. The primary outcome was a first CVE occurring between January 2001 and December 2020.Methods:Three CVD risk scores were computed at baseline. The performance of the original and modified (*1.5 multiplication factor) CV risk algorithms were assessed. Time-varying Cox proportional hazard models and Kaplan–Meier survival analysis were used to assess whether inflammatory burden (Bath ankylosing spondylitis disease activity index [BASDAI] and inflammatory markers), nonsteroidal anti-inflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs) can predict the development of first CVE.Results:463 patients (35 [26–45] years, male: 360 [77.8%]) were recruited. After a median follow-up of 12 (7–19) years, 61 patients (13.2%) experienced a first CVE. Traditional/modified CV risk scores underestimated CV risk. Erythrocyte sedimentation rate (ESR) ⩾ 20 mm/h was associated with a significantly higher risk of CVE during follow-up (HR: 2.07, 95%CI [1.10, 3.98], p = 0.008). Active disease as indicated by a rising BASDAI also showed positive trend towards a higher risk of developing CVE over time. After adjusting for CV risk scores in the multivariable models, high ESR level (ESR ⩾ 20 mm/h) over time remained significantly associated with a higher risk of developing CV events.Conclusion:Increased inflammatory burden as reflected by elevated ESR levels (ESR ⩾ 20) was associated with increased risk of CVE, while the use of NSAIDs and DMARDs were not.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-08T08:30:56Z
      DOI: 10.1177/1759720X221122401
      Issue No: Vol. 14 (2022)
       
  • Normal C-reactive protein in active psoriatic arthritis: results from
           real-world clinical practice

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      Authors: Chrysoula G. Gialouri, Gerasimos Evangelatos, Maria Pappa, Anastasios Karamanakos, Alexios Iliopoulos, Maria G. Tektonidou, Petros P. Sfikakis, George E. Fragoulis
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:The value of normal C-reactive protein (CRP) in psoriatic arthritis (PsA) is debatable.Objectives:To test the hypothesis that CRP is frequently normal in contemporary real-world PsA patients, despite active disease.Design:In this cross-sectional study, patients were divided into two groups: CRP ⩽ 0.5 mg/dl (normal) and CRP > 0.5 mg/dl (increased). Having as dependent variable the CRP status, these groups were compared for disease-related features, including composite disease activity indices [clinical Disease Activity in PSoriatic Arthritis (cDAPSA) and minimal disease activity (MDA)] and patient-reported outcomes (PROs). Agreement between CRP status and cDAPSA/MDA scores was calculated (Cohen’s kappa).Methods:Data from consecutive PsA patients attending two outpatient rheumatology clinics (January 2019–June 2021) were analysed.Results:From 128 patients enrolled (51.6% females; mean ± standard deviation age: 53.4 ± 11.7 years; 23.4%, 48.4% and 64.1% treated with glucocorticoids, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs, respectively), two-thirds (66.4%, n = 85) had normal CRP values. CRP status was not associated with any of the disease-related parameters and PROs, but only with ESR [odds ratio: 1.04 (95% confidence interval: 1.01–1.06), p = 0.005]. Among patients with normal CRP, 45.9% (39/85) were on non-MDA state, while 21.2% (18/85) had cDAPSA-moderate and 5.9% (5/85) had cDAPSA-high disease activities. Conversely, 54.2% (39/72) of patients on non-MDA state and 52.3% (23/44) of those with cDAPSA-moderate or cDAPSA-high disease activity had normal CRP values. Cohen’s kappa between normal CRP and MDA, cDAPSA-remission, and cDAPSA-remission/low disease activity was –0.26, –0.21 and –0.22, respectively, displaying total disagreement.Conclusion:Normal CRP in PsA should not be used as surrogate marker of remission or low/MDA, therefore needs to be interpreted with caution in clinical decision-making.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-05T07:06:10Z
      DOI: 10.1177/1759720X221122417
      Issue No: Vol. 14 (2022)
       
  • Uveitis in peripheral spondyloarthritis patients: an ancillary analysis of
           the ASAS-PerSpA study

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      Authors: Maria Llop, Jordi Gratacós, Mireia Moreno, Marta Arévalo, Joan Calvet, Maxime Dougados, Clementina López-Medina
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Acute anterior uveitis (AAU) is the most frequent extra-musculoskeletal manifestation in spondyloarhtritis (SpA). Previous data on AAU focused on axial disease; therefore, it is not well known whether the clinical characteristics of patients with AAU and recurrent AAU differ between patients with axial and peripheral SpA.Objective:Primary objective was to compare the clinical characteristics of patients with AAU from patients without AAU in axial and peripheral spondyloarthritis (SpA) patients. Secondary objectives were to describe the clinical features of patients with AAU in the subset of patients with peripheral SpA (pSpA) and the clinical characteristics of patients with recurrent AAU in SpA patients.Design:This is an ancillary analysis of the ASAS-PerSpA study which included 3152 patients, 2719 patients with axSpA and 433 with pSpA according to rheumatologist judgement.Methods:Recurrent AAU was defined as the presence of two or more episodes of AAU ever. Univariable and multivariable binary logistic regression analyses were conducted to identify factors associated with the presence of AAU ever and the presence of recurrent AAU.Results:Overall, 663 patients (21%) presented AAU. Of them, 444 (66.9%) presented recurrent episodes. In patients with SpA, HLA-B27 positivity is the most important factor linked to the presence of AAU, odds ratio (OR) = 2.70 (95% CI = 2.04–3.6). In patients with pSpA, HLA-B27 positivity was also the most relevant factor linked to the presence of AAU, OR = 6.08 (95% CI = 2.72–15.68). Moreover, disease duration, younger age and higher body mass index (BMI) were the only factors slightly linked to the presence of recurrent episodes, OR = 1.03 (95% CI = 1.01–1.04), OR = 1.01 (95% CI = 1.00–1.03) and OR = 1.04 (95% CI = 1.01–1.08), respectively.Conclusion:HLA-B27 positivity is the most relevant factor linked to AAU risk in SpA patients, and this association is even stronger in those patients with pSpA. Moreover, our study did not find an association between HLA-B27 positivity and recurrent AAU in SpA patients.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-05T07:04:29Z
      DOI: 10.1177/1759720X221119246
      Issue No: Vol. 14 (2022)
       
  • Frequency and anatomic distribution of magnetic resonance imaging lesions
           in the sacroiliac joints of spondyloarthritis and non-spondyloarthritis
           patients

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      Authors: Sophie Hecquet, Jean-Philippe Lustig, Frank Verhoeven, Mickaël Chouk, Sébastien Aubry, Daniel Wendling, Clément Prati
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Lesions detected by magnetic resonance imaging (MRI) of the sacroiliac joints are critical to the diagnosis of non-radiographic axial spondyloarthritis. However, inflammatory and structural lesions may be encountered in other conditions.Objectives:The objective of this study was to evaluate and compare the frequency and localization of inflammatory and structural lesions on MRIs of the sacroiliac joint of spondyloarthritis (SpA) and non-spondyloarthritis (non-SpA) patients.Design:This is a retrospective study including 200 patients, each having undergone an MRI of the sacroiliac joints.Methods:Two experienced readers evaluated the whole set of images to detect erosions, subchondral sclerosis, fatty lesions, bone marrow edema (BME) and ankylosis according to the definitions established by the ASAS MRI working group. We divided sacroiliac joints into five segments: upper, antero-middle, intermediate-middle, postero-middle and lower.Results:A total of 96 subjects with SpA (mean age 37.4 ± 11.8 years) and 104 without SpA (mean age 39.9 ± 11.6 years) were included. Of the 96 SpA patients, 65% had inflammatory buttock pain compared with 25% in the non-SpA group. BME was seen in 65% of SpA patients, mainly in the intermediate-middle segment, and in 20% of non-SpA patients, predominantly in the antero-middle segment. Subchondral sclerosis occurred in 44% of non-SpA patients, mostly in the antero-middle segment, and in 36% of SpA patients. Fatty lesions were present in 34% of SpA and in 21% of non-SpA patients. Erosions were seen in 25% of non-SpA and in 60% of SpA patients. BME and structural lesions were minimally observed in the postero-middle segment in non-SpA patients.Conclusion:Inflammatory and structural lesions were observed in all segments of the joint in SpA, mainly in the middle segments, while lesions predominantly affected the antero-middle segment in non-SpA, and were uncommon in the postero-middle segment.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-05T07:02:49Z
      DOI: 10.1177/1759720X221119245
      Issue No: Vol. 14 (2022)
       
  • Successful treatment of severe COVID-19 pneumonia, a case series with
           simultaneous interleukin-1 and interleukin-6 blockade with 1-month
           follow-up

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      Authors: Hildrun Haibel, Denis Poddubnyy, Stefan Angermair, Kristina Allers, Janis L. Vahldiek, Michael Schumann, Thomas Schneider
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Interleukin (IL)-6 and IL-1 blockade showed beneficial results in patients with severe COVID-19 pneumonia and evidence of cytokine release at the early disease stage. Here, we report outcomes of open-label therapy with a combination of blocking IL-6 with tocilizumab 8 mg/kg up to 800 mg and IL-1 receptor antagonist anakinra 100–300 mg over 3–5 days. Thirty-one adult patients with severe COVID-19 pneumonia and signs of cytokine release, mean age 54 (30–79) years, 5 female, 26 male, and mean symptom duration 6 (3–10) days were treated. Patients with more than 10 days of symptoms, evidence of bacterial infection/elevated procalcitonin and other severe lung diseases were excluded. Computed tomography (CT) scans of the lung were performed initially and after 1 month; inflammatory activity was assessed on a scale 0–25. Twenty-five patients survived without intubation and mechanical lung ventilation, two patients died. C-reactive protein decreased in 19/31 patients to normal ranges. The mean activity CT score decreased from 14 (8–20) to 6 (0–16, n = 16). In conclusion, most of our patients recovered fast and sustained, indicating that early interruption of cytokine release might be very effective in preventing patients from mechanical ventilation, death, and long-term damage.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-05T06:59:08Z
      DOI: 10.1177/1759720X221116405
      Issue No: Vol. 14 (2022)
       
  • New insights on multigenic autoinflammatory diseases

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      Authors: Petros Efthimiou, Olga Petryna, Priscila Nakasato, Apostolos Kontzias
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Autoinflammatory diseases are disorders of the innate immune system, which can be either monogenic due to a specific genetic mutation or complex multigenic due to the involvement of multiple genes. The aim of this review is to explore and summarize the recent advances in pathogenesis, diagnosis, and management of genetically complex autoinflammatory diseases, such as Schnitzler’s syndrome; adult-onset Still’s disease; synovitis, acne, pustulosis, hyperostosis, osteitis syndrome/chronic recurrent multifocal osteomyelitis/chronic non-bacterial osteomyelitis; Adamantiades-Behçet’s disease; Yao syndrome; and periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome. The PubMed database was screened for relevant articles using free text words and specific search strings. The search was limited to English-language articles, reporting the results of studies in humans, published through March 2021. Evidence from literature suggest that these rare multigenic autoinflammatory diseases can present with different clinical features and the diagnosis of these diseases can be challenging due to a combination of nonspecific manifestations that can be seen in a variety of other conditions. Diagnostic delays and disease complications may occur due to low disease awareness and the lack of pathognomonic markers. The pathogeneses of these diseases are complex and in some cases precise pathogenesis is not clearly understood. Conventional treatments are commonly used for the management of these conditions, but biologics have shown promising results. Biologics targeting proinflammatory cytokines including IL-1, IL-6, TNF-α, IL-17A and IL-18 have been shown to ameliorate signs and symptoms of different multigenic autoinflammatory diseases.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-09-03T10:11:22Z
      DOI: 10.1177/1759720X221117880
      Issue No: Vol. 14 (2022)
       
  • Effectiveness and safety of a biosimilar-to-biosimilar switch of the TNF
           inhibitor etanercept in patients with chronic inflammatory rheumatic
           diseases

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      Authors: Uta Kiltz, Styliani Tsiami, Xenofon Baraliakos, Ioana Andreica, David Kiefer, Jürgen Braun
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Biosimilar disease-modifying anti-rheumatic drugs (bsDMARDs) has created a financial incentive to encourage switching to cheaper products.Objectives:We aim to study the effectiveness and safety of a non-medical bsDMARD-to-bsDMARD switch from originator etanercept (ETN) to bsDMARD ETN (SB4) and successive to another bsDMARD ETN (GP2015) in patients with chronic inflammatory rheumatic diseases in a real-life setting.Methods:Retrospective chart review of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) who had been treated with originator ETN and were switched twice to ETN bsDMARD for non-medical reasons thereafter. All patients received ETN 50 mg/week. Disease activity and physical function was assessed every 12 weeks with standardized questionnaires.Results:A total of 100 patients who switched twice [54 RA, 27 axSpA, 19 PsA, mean age 54.3 (15.1), 46% male] were included. Patients with axSpA were younger than RA and PsA patients. Patients with SpA were less likely to receive conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than RA patients. Duration of treatment with originator ETN before the first switch was 3.3 (2.3) years. Retention rate 6 months after the second ETN bsDMARD switch was 89%. Disease activity and physical function scores remained rather unchanged in patients with RA and axSpA longitudinally, while there was some more fluctuation in PsA patients. Six patients lost efficacy and were switched back to originator ETN in month 6 (n = 4) or to another mode of action (n = 2). There were 14 adverse events (AE) reported in eight patients. One patient re-administered bsDMARD GP2015 successfully 3 months after healing of mucosal erosions.Conclusion:No relevant change in disease activity and physical function were observed in a non-medical bsDMARD-to-bsDMARD switch scenario. The retention rate after switches from originator ETN to two ETN bsDMARD was close to 90%. Multiple switches resulted in a high adherence rate without clinically important efficacy or safety signals.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-26T12:46:48Z
      DOI: 10.1177/1759720X221119593
      Issue No: Vol. 14 (2022)
       
  • MRI lesions in SpA: a comparison with noninflammatory back pain using
           propensity score adjustment method

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      Authors: Ho Yin Chung, Jin Xian Huang, Kam Ho Lee, Helen Hoi Lun Tsang, Chak Sing Lau, Shirley Chiu Wai Chan
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Magnetic resonance imaging (MRI) is important in the management of axial spondyloarthritis (SpA). However, many MRI lesions are not exclusive to axial SpA. Further characterization of these lesions may lead to better clinical decisions.Objective:The objective of this study was to compare the frequency of individual spinal MRI lesions between axial SpA and noninflammatory back pain. The factors associated with individual lesions in participants with axial SpA were also determined.Design:This was a cross-sectional observational study.Methods:MRI lesions in 447 participants with axial SpA and 122 participants with noninflammatory back pain were compared using the propensity score adjustment method. Individual lesions included discovertebral lesions (DVL), Modic type 1 lesions, DVL without Modic type 1 lesions, facet joint lesions, costovertebral joint lesions, corner inflammatory lesions (CIL), and fatty corner lesions (FCL). The factors associated with the lesions were determined using regression analyses.Results:Among participants with axial SpA, 81.9% were HLA-B27-positive, 55.0% had radiographic axial SpA, and 60.5% had radiographic features of spinal damage (mSASSS>2). Almost half (48.6% in axial SpA versus 31.1% in noninflammatory back pain) had inflammatory lesions on spinal MRI. In propensity score matching with noninflammatory back pain, axial SpA had an increased occurrence of DVL without Modic type 1 lesion (OR = 3.43, p = 0.01), costovertebral lesion (OR = 11.89, p = 0.02), number of CIL (B = 1.19, p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-25T12:30:36Z
      DOI: 10.1177/1759720X221119250
      Issue No: Vol. 14 (2022)
       
  • Open questions on the management of targeted therapies for the treatment
           of systemic sclerosis-interstitial lung disease: results of a EUSTAR
           survey based on a systemic literature review

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      Authors: Corrado Campochiaro, Maria Grazia Lazzaroni, Cosimo Bruni, Elisabetta Zanatta, Giacomo De Luca, Marco Matucci-Cerinic
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:The results of randomized controlled (RCT) and retrospective studies have expanded the armamentarium of drugs for systemic sclerosis (SSc) – interstitial lung disease (ILD) treatment. The correct positioning of these drugs is not yet clarified.Objectives:Systemic literature review (SLR) on rituximab (RTX), tocilizumab (TCZ), nintedanib and abatacept (ABT) for the treatment of SSc-ILD. The results of the SLR were used to create a dedicated survey.Design:The study was performed as a systematic review.Data sources and methods:the SLR was performed using the following terms: “(systemic sclerosis OR scleroderma) AND (interstitial lung disease OR lung fibrosis OR pulmonary fibrosis) AND (rituximab OR tocilizumab OR abatacept OR nintedanib)”. The results of the SLR were integrated in a survey including 8 domains. These were sent to all EUSTAR members and to the participants of the 2020 Scleroderma World Congress.Results:41 studies (34 on RTX, 5 on TCZ, 2 on ABT, and 1 on nintedanib) were identified. RCTs supported the use of TCZ and nintedanib, while retrospective studies supported the use of RTX for SSc-ILD. No clear data were obtained about ABT. The survey showed that RTX is the most available option (96%) whereas the most frequent reason for targeted therapy introduction is lung progression while on csDMARDs (86% RTX, 59% TCZ and 63% nintedanib). Combination therapy was the most frequently mentioned therapeutic scheme for nintedanib (75%) and RTX (63%). Physicians’ perception of safety was similar for all drugs, while drug efficacy was the same for RTX and nintedanib, followed by TCZ (4.8 ± 2). The most frequently raised concerns pertained to efficacy, safety and combination regimens.Conclusion:Our SLR supports the use of RTX, TCZ and nintedanib for SSc-ILD patients and underlines the need for more data about upfront combination versus monotherapy. It also highlighted the need to identify predictors supporting drug choice according to both pulmonary and extra-pulmonary manifestations.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-23T06:34:44Z
      DOI: 10.1177/1759720X221116408
      Issue No: Vol. 14 (2022)
       
  • Relationship between onset of psoriasis and spondyloarthritis symptoms
           with clinical phenotype and diagnosis: data from REGISPONSER registry

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      Authors: Ignacio Gómez-Garcia, Teresa García-Puga, Pilar Font-Ugalde, Maria Angeles Puche-Larrubia, Nuria Barbarroja, Patricia Ruiz-Limón, Alejandro Escudero-Contreras, Eduardo Collantes-Estévez, Clementina López-Medina
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:The relationship of psoriasis and spondyloarthritis (SpA) is well-known, and the age of appearance of different manifestations has been described as a determinant of SpA phenotype. However, differences between Spa with psoriasis and psoriatic arthritis (PsA) are still controversial.Objectives:To evaluate whether the time of onset of psoriasis relative to the appearance of rheumatic symptoms in patients with SpA is associated with a clinical phenotype, a rheumatologist’s diagnosis and the evolution of the disease.Design:This was a cross-sectional study with data extracted from the REGISPONSER (Spondyloarthritis Registry of the Spanish Rheumatology Society) registry.Methods:All patients had data available for both psoriasis and SpA dates of onset. Patients were classified into two groups depending on the time of appearance of psoriasis: psoriasis before or after rheumatic symptoms. The clinical characteristics, disease activity, radiographic damage, functional ability and received treatments were compared between the two groups. Moreover, the rheumatologists’ diagnoses were compared between the two groups. Univariate and multivariate logistic regressions were conducted to evaluate the factors associated with each group.Results:A total of 433/2367 (18.3%) patients included in the REGISPONSER database had psoriasis: 330 (76.2%) patients had psoriasis before rheumatic symptoms, and 103 (23.8%) had psoriasis after rheumatic symptoms. Patients with psoriasis before rheumatic symptoms had a shorter disease duration and a lower body mass index, a lower prevalence of both HLA-B27 antigens and anterior uveitis, a higher prevalence of dactylitis and an increase in levels of the erythrocyte sedimentation rate (ESR). Furthermore, a higher prevalence of PsA diagnoses (78.1% versus 56.4%) and a more frequent fulfilment of the CASPAR criteria (57.5% versus 42.2%) were found in these patients. The use of DMARDs was not significantly different between the two groups.Conclusion:The time of appearance of psoriasis is associated with the clinical phenotype of SpA and could determine a diagnosis of PsA by rheumatologists.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-22T11:53:05Z
      DOI: 10.1177/1759720X221118055
      Issue No: Vol. 14 (2022)
       
  • Validation of the Simplified Disease Activity Index (SDAI) with a quick
           quantitative C-reactive protein assay (SDAI-Q) in patients with rheumatoid
           arthritis: a prospective multicenter cross-sectional study

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      Authors: Julia Schally, Henning Christian Brandt, Jan Brandt-Jürgens, Gerd R. Burmester, Hildrun Haibel, Henriette Käding, Kirsten Karberg, Susanne Lüders, Burkhard Muche, Mikhail Protopopov, Valeria Rios Rodriguez, Murat Torgutalp, Maryna Verba, Silke Zinke, Denis Poddubnyy, Fabian Proft
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:The Simplified Disease Activity Index (SDAI) is a recommended composite score for assessing the remission status in patients with rheumatoid arthritis (RA). However, determination of C-reactive protein (CRP) levels takes several hours and sometimes days and limits the use of the SDAI in the clinical setting. The aim of this study was to validate the SDAI using a quick quantitative C-reactive protein (qCRP) assay (as SDAI-Q) in RA patients.Design:This is a multicenter, prospective, cross-sectional pilot study in RA patients.Methods:Adult patients (⩾18 years) with a clinical diagnosis of RA were recruited between January 2020 and September 2020 from five rheumatologic centers located in Berlin, Germany. SDAI, SDAI-Q, Clinical Disease Activity Index (CDAI), and DAS28 scores comprising CRP, qCRP, or erythrocyte sedimentation rate (ESR) were calculated. The agreement of disease activity categories was analyzed using cross tabulations and weighted Cohen’s kappa. The agreement of numerical values was analyzed with Bland–Altman plots and intraclass correlation coefficients (ICCs).Results:Overall, 100 RA patients were included in the statistical analysis. The mean value of qCRP (7.89 ± 16.98 mg/l) was slightly higher than that of routine laboratory CRP (6.97 ± 15.02 mg/l). Comparing SDAI and SDAI-Q, all patients were assigned to identical disease activity categories. Agreement of disease activity categories by CDAI and SDAI/SDAI-Q was observed in 93% with a weighted Cohen’s kappa of 0.929 (95% confidence interval (CI) = 0.878; 0.981).Conclusion:The SDAI-Q showed an absolute agreement regarding the assignment of disease activity categories in comparison with the conventional SDAI. Therefore, the SDAI-Q may facilitate the application of a treat-to-target concept in clinical trials and clinical routine as a quickly available disease activity score incorporating CRP as an objective parameter.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-16T12:38:06Z
      DOI: 10.1177/1759720X221114107
      Issue No: Vol. 14 (2022)
       
  • Managing inadequate response to initial anti-TNF therapy in rheumatoid
           arthritis: optimising treatment outcomes

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      Authors: Peter C. Taylor, Marco Matucci Cerinic, Rieke Alten, Jérôme Avouac, Rene Westhovens
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Anti-tumour necrosis factors (anti-TNFs) are established as first-line biological therapy for rheumatoid arthritis (RA) with over two decades of accumulated clinical experience. Anti-TNFs have well established efficacy/safety profiles along with additional benefits on various comorbidities. However, up to 40% of patients may respond inadequately to an initial anti-TNF treatment because of primary non-response, loss of response, or intolerance. Following inadequate response (IR) to anti-TNF treatment, clinicians can consider switching to an alternative anti-TNF (cycling) or to another class of targeted drug with a different mechanism of action, such as Janus kinase inhibitors, interleukin-6 receptor blockers, B-cell depletion agents, and co-stimulation inhibitors (swapping). While European League Against Rheumatism recommendations for pharmacotherapeutic management of RA, published in 2020, are widely regarded as helpful guides to clinical practice, they do not provide any clear recommendations on therapeutic choices following an IR to first-line anti-TNF. This suggests that both cycling and swapping treatment strategies are of equal value, but that the treating physician must take the patient’s individual characteristics into account. This article considers which patient characteristics influence clinical decision-making processes, including the reason for treatment failure, previous therapies, comorbidities, extra-articular manifestations, pregnancy, patient preference and cost-effectiveness, and what evidence is available to support decisions made by the physician.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-16T12:36:12Z
      DOI: 10.1177/1759720X221114101
      Issue No: Vol. 14 (2022)
       
  • Acute effects of exercise on pain symptoms, clinical inflammatory markers
           and inflammatory cytokines in people with rheumatoid arthritis: a
           systematic literature review

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      Authors: Christopher Balchin, Ai Lyn Tan, Joshua Golding, Lesley-Anne Bissell, Oliver J. Wilson, Jim McKenna, Antonios Stavropoulos-Kalinoglou
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Exercise is advocated in the treatment of rheumatoid arthritis (RA). However, uncertainty around the acute effects of exercise on pain and inflammation may be stopping people with RA from exercising more regularly.Objectives:To determine the acute effects of exercise on pain symptoms, clinical inflammatory markers, and inflammatory cytokines in RA.Design:A systematic review of the literature.Data sources and methods:Five databases were searched (PubMed, Cochrane Library, CINAHL, Scopus and SPORTDiscus); inclusion criteria were studies with acute exercise, a definite diagnosis of RA and disease characteristics assessed by clinical function (i.e., disease activity score, health assessment questionnaire and self-reported pain), clinical markers associated with inflammation (i.e., c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), and inflammatory cytokines (i.e., interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)).Results:From a total of 1544 articles, initial screening and full text assessment left 11 studies meeting the inclusion criteria. A total of 274 people were included in the studies (RA = 186; control = 88). Acute bouts of aerobic, resistance, and combined aerobic and resistance exercise did not appear to exacerbate pain symptoms in people with RA.Conclusion:Post-exercise responses for pain, clinical inflammatory markers and inflammatory cytokines were not different between people with or without RA. Exercise prescription was variable between studies, which limited between-study comparisons. Therefore, future investigations in people with RA are warranted, which combine different exercise modes and intensities to examine acute effects on pain symptoms and inflammatory markers.Registration:The PROSPERO international prospective register of systematic reviews – CRD42018091155.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-16T12:29:43Z
      DOI: 10.1177/1759720X221114104
      Issue No: Vol. 14 (2022)
       
  • Stromal vascular fraction therapy for knee osteoarthritis: a systematic
           review

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      Authors: Anna Boada-Pladellorens, Mercè Avellanet, Esther Pages-Bolibar, Anna Veiga
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Regenerative cell therapies, such as adipose-derived stromal vascular fraction (SVF), have been postulated as potential treatments for knee osteoarthritis (KOA).Objectives:To assess the efficacy and safety of SVF treatment against placebo and other standard therapies for treating KOA in adult patients.Design:A systematic review.Data sources and methods:We searched the following databases: MEDLINE via PubMed, Epistemonikos, PEDro, DynaMed, TripDatabase, Elsevier via Clinicalkey and Cochrane Controlled Trials Register. We included prospective interventional studies where treatment with SVF in adults with KOA was compared against placebo or other standard therapies, and results were objectively measured with at least one widely recognised osteoarthritis scale.Results:Among 266 studies published until May 2021, nine met our inclusion criteria. A total of 239 patients (274 knees) were included in our study. The follow-up ranged from 6 to 24 months. Six studies had a control group (only one being placebo). All studies showed that SVF improved pain and functionality measured, in most cases, with the visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index. In addition, five studies reported an improvement in anatomical structures, as detected in MR images. However, the number of cells contained in SVF varied substantially between different studies, which could induce a comparison bias.Conclusion:Although based on a small number of dissimilar studies, SVF was considered a safe treatment for KOA and could be promising in terms of pain, functionality and anatomical structure improvement. However, SVF products need to be standardised, the number of cells homogenised and the use of concomitant treatments reduced to establish proper comparisons.Registration:PROSPERO registration number: CRD42021284187.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-16T11:05:47Z
      DOI: 10.1177/1759720X221117879
      Issue No: Vol. 14 (2022)
       
  • Cardiovascular risk associated with allopurinol or benzbromarone treatment
           in patients with gout

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      Authors: Yeonghee Eun, Heewon Han, Kyunga Kim, Seonyoung Kang, Seulkee Lee, Hyungjin Kim, Jaejoon Lee, Eun-Mi Koh, Hoon-Suk Cha
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:In previous studies, cardiovascular (CV) risk was increased in patients with gout. The effects of uric acid–lowering therapy on CV risk in gout patients have been investigated in numerous studies; however, allopurinol and benzbromarone have rarely been compared.Objectives:To compare CV risk based on allopurinol and benzbromarone treatment in Korean gout patients.Design:A nationwide population-based retrospective cohort study.Methods:We used South Korea database of the Health Insurance Review and Assessment (HIRA) service to identify gout patients ⩾18 years of age who newly started allopurinol or benzbromarone between 2009 and 2015. The primary outcome of the study was the occurrence of a composite CV endpoint, which included coronary revascularization, hospitalization due to myocardial infarction, ischemic stroke, and transient ischemic attack. Cox proportional hazard regression analysis and Kaplan–Meier curves were used for analysis.Results:The study included 257,097 allopurinol initiators and 7868 benzbromarone initiators. Compared with allopurinol initiators, the adjusted hazard ratio (aHR) of the composite CV endpoint of benzbromarone initiators was 1.01 [95% confidence interval (CI): 0.83−1.21], which was not significantly different. The results did not change even when 1:3 propensity score matching was performed for baseline characteristics. In subgroup analysis of high-risk patients with CV disease, significant difference was not observed between allopurinol and benzbromarone initiators.Conclusion:In this study, significant difference was not found in CV risk between allopurinol and benzbromarone initiators. In the high-CV-risk group, the incidence of CV events did not differ between allopurinol and benzbromarone initiators.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-10T12:33:46Z
      DOI: 10.1177/1759720X221116409
      Issue No: Vol. 14 (2022)
       
  • A broad look into the future of systemic sclerosis

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      Authors: Gabriela Riemekasten, Jörg H.W. Distler
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Systemic sclerosis (SSc) is a systemic autoimmune disease with the key features of inflammation, vasculopathy and fibrosis. This article focussed on emerging fields based on the authors’ current work and expertise. The authors provide a hierarchical structure into the studies of the pathogenesis of SSc starting with the contribution of environmental factors. Regulatory autoantibodies (abs) are discussed, which are parts of the human physiology and are specifically dysregulated in SSc. Abs against the angiotensin II receptor subtype 1 (AT1R) and the endothelin receptor type A (ETAR) are discussed in more detail. Extracellular vesicles are another novel player to possess disease processes. Fibroblasts are a key effector cell in SSc. Therefore, the current review will provide an overview about their plasticity in the phenotype and function. Promising nuclear receptors as key regulators of transcriptional programmes will be introduced as well as epigenetic modifications, which are pivotal to maintain the profibrotic fibroblast phenotype independent of external stimuli. Fibroblasts from SSc patients exhibit a specific signalling and reactivate developmental pathways and stem cell maintenance such as by employing hedgehog and WNT, which promote fibroblast-to-myofibroblast transition and extracellular matrix generation. Pharmacological interventions, although for other indications, are already in clinical use to address pathologic signalling.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-08-09T12:51:36Z
      DOI: 10.1177/1759720X221109404
      Issue No: Vol. 14 (2022)
       
  • A glance into the future of gout

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      Authors: Francisca Sivera, Mariano Andres, Nicola Dalbeth
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Gout is characterized by monosodium urate (MSU) crystal deposits in and within joints. These deposits result from persistent hyperuricaemia and most typically lead to recurrent acute inflammatory episodes (gout flares). Even though some aspects of gout are well characterized, uncertainties remain; this upcoming decade should provide further insights into many of these uncertainties. Synovial fluid analysis allows for the identification of MSU crystals and unequivocal diagnosis. Non-invasive methods for diagnosis are being explored, such as Raman spectroscopy and imaging modalities. Both ultrasound and dual-energy computed tomography (DECT) allow the detection of MSU crystals; this not only provides a mean of diagnosis, but also has furthered gout knowledge defining the presence of a preclinical deposition in asymptomatic hyperuricaemia. Scientific consensus establishes the beginning of gout as the beginning of symptoms (usually the first flare), but the concept is currently under review. For effective long-term gout management, the main goal is to promote crystal dissolution treatment by reducing serum urate below 6 mg/dL (or 5 mg/dL if faster crystal dissolution is required). Current urate-lowering therapies’ (ULTs) options are limited, with allopurinol and febuxostat being widely available, and probenecid, benzbromarone, and pegloticase available in some regions. New xanthine oxidase inhibitors and, especially, uricosurics inhibiting urate transporter URAT1 are under development; it is probable that the new decade will see a welcomed increase in the gout therapeutic armamentarium. Cardiovascular and renal comorbidities are common in gout patients. Studies determining whether optimal treatment of gout will positively impact these comorbidities are currently lacking, but will hopefully be forthcoming. Overall, the single change that will most impact gout management is greater uptake of international rheumatology society recommendations. Innovative strategies, such as nurse-led interventions based on these recommendations have recently demonstrated treatment success for people with gout.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-28T10:52:50Z
      DOI: 10.1177/1759720X221114098
      Issue No: Vol. 14 (2022)
       
  • Risk of ischaemic stroke among new users of glucosamine and chondroitin
           sulphate: a nested case–control study

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      Authors: Ramón Mazzucchelli, Sara Rodríguez-Martín, Natalia Crespí-Villarías, Alberto García-Vadillo, Miguel Gil, Laura Izquierdo-Esteban, Antonio Rodríguez-Miguel, Diana Barreira-Hernández, Encarnación Fernández-Antón, Alberto García-Lledó, Aina Pascual, Marianna Vitaloni, Josep Vergés, Francisco J. de Abajo
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Several studies have reported that the use of chondroitin sulphate (CS) and glucosamine may reduce the risk of acute myocardial infarction. Although it is thought that this potential benefit could be extended to ischaemic stroke (IS), the evidence is scarce.Objective:To test the hypothesis that the use of prescription glucosamine or CS reduces the risk of IS.Design:Case–control study nested in an open cohort.Methods:Patients aged 40–99 years registered in a Spanish primary healthcare database (BIFAP) during the 2002–2015 study period. From this cohort, we identified incident cases of IS, applying a case-finding algorithm and specific validation procedures, and randomly sampled five controls per case, individually matched with cases by exact age, gender and index date. Adjusted odds ratios (AORs) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of glucosamine or CS were considered.Results:A total of 13,952 incident cases of IS and 69,199 controls were included. Of them, 106 cases (0.76%) and 803 controls (1.16%) were current users of glucosamine or CS at index date, yielding an AOR of 0.66 (95% CI: 0.54–0.82) (for glucosamine, AOR: 0.55; 95% CI: 0.39–0.77; and for CS, AOR: 0.77; 95% CI: 0.60–0.99). The reduced risk among current users was observed in both sexes (men, AOR: 0.69; 95% CI: 0.49–0.98; women, AOR: 0.65; 95% CI: 0.50–0.85), in individuals above and below 70 years of age (AOR: 0.69; 95% CI: 0.53–0.89 and AOR: 0.59; 95% CI: 0.41–0.85, respectively), in individuals with vascular risk factors (AOR: 0.53; 95% CI: 0.39–0.74) and among current/recent users of nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR: 0.71; 95% CI: 0.55–0.92). Regarding duration, the reduced risk was observed in short-term users (364 days AOR: 0.86; 95% CI: 0.57–1.31).Conclusions:Our results support a protective effect of prescription CS and glucosamine in IS, which was observed even in patients at vascular risk.Mini abstractOur aim was to analyse whether the use of glucosamine or chondroitin sulphate (CS) reduces the risk of ischaemic stroke (IS). We detected a significant decrease.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-26T11:52:08Z
      DOI: 10.1177/1759720X221113937
      Issue No: Vol. 14 (2022)
       
  • A pilot study on deep learning-based grading of corners of vertebral
           bodies for assessment of radiographic progression in patients with
           ankylosing spondylitis

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      Authors: Bon San Koo, Jae Joon Lee, Jae-Woo Jung, Chang Ho Kang, Kyung Bin Joo, Tae-Hwan Kim, Seunghun Lee
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Radiographs are widely used to evaluate radiographic progression with modified stoke ankylosing spondylitis spinal score (mSASSS).Objective:This pilot study aimed to develop a deep learning model for grading the corners of the cervical and lumbar vertebral bodies for computer-aided detection of mSASSS in patients with ankylosing spondylitis (AS).Methods:Digital radiographic examination of the spine was performed using Discovery XR656 (GE Healthcare) and Digital Diagnost (Philips). The disk points were detected between the bodies using a key-point detection deep learning model from the image obtained in DICOM (digital imaging and communications in medicine) format from the cervical and lumbar spinal radiographs. After cropping the vertebral regions around the disk point, the lower and upper corners of the vertebral bodies were classified as grade 3 (total bony bridges) or grades 0, 1, or 2 (non-bridges). We trained a convolutional neural network model to predict the grades in the lower and upper corners of the vertebral bodies. The performance of the model was evaluated in a validation set, which was separate from the training set.Results:Among 1280 patients with AS for whom mSASSS data were available, 5,083 cervical and 5245 lumbar lateral radiographs were reviewed. The total number of corners where mSASSS was measured in the cervical and lumbar vertebrae, including the upper and lower corners, was 119,414. Among them, the number of corners in the training and validation sets was 110,088 and 9326, respectively. The mean accuracy, sensitivity, and specificity for mSASSS scoring in one corner of the vertebral body were 0.91604, 0.80288, and 0.94244, respectively.Conclusion:A high-performance deep learning model for grading the corners of the vertebral bodies was developed for the first time. This model must be improved and further validated to develop a computer-aided tool for assessing mSASSS in the future.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-22T12:11:49Z
      DOI: 10.1177/1759720X221114097
      Issue No: Vol. 14 (2022)
       
  • Tocilizumab in visual involvement of giant cell arteritis: a multicenter
           study of 471 patients

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      Authors: Javier Loricera, Santos Castañeda, Clara Moriano, Javier Narváez, Vicente Aldasoro, Olga Maiz, Rafael Melero, Ignacio Villa, Paloma Vela, Susana Romero-Yuste, José L. Callejas, Eugenio de Miguel, Eva Galíndez-Agirregoikoa, Francisca Sivera, Jesús C. Fernández-López, Carles Galisteo, Iván Ferraz-Amaro, Julio Sánchez-Martín, Lara Sánchez-Bilbao, Mónica Calderón-Goercke, Alfonso Casado, José L. Hernández, Miguel A. González-Gay, Ricardo Blanco
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial.Objective:We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ.Design:This is an observational multicenter study of patients with GCA treated with TCZ.Methods:Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision.Results:Four hundred seventy-one GCA patients (mean age, 74 ± 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL (n = 60; unilateral/bilateral: 48/12), TVL (n = 17; unilateral/bilateral: 11/6), diplopia (n = 2), and blurred vision (n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved.Conclusion:TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-22T12:10:09Z
      DOI: 10.1177/1759720X221113747
      Issue No: Vol. 14 (2022)
       
  • The association of depression and anxiety with treatment outcomes in
           patients with rheumatoid arthritis – a pooled analysis of five
           randomised controlled trials

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      Authors: Arkady T. Manning-Bennett, Ashley M. Hopkins, Michael J. Sorich, Susanna M. Proudman, David J.R. Foster, Ahmad Y. Abuhelwa, Michael D. Wiese
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Rheumatoid arthritis (RA) is an inflammatory autoimmune condition associated with an increased risk of developing depression and anxiety. Depression and anxiety are associated with worse outcomes in RA, but the magnitude of the effect of each condition on RA outcomes is unclear. It is also unknown how pharmacological treatment of depression affects RA outcomes.Objective:The primary aim of this study was to investigate the association of comorbid depression and anxiety with remission in patients with RA. Secondary aims were to determine the association between comorbid depression and anxiety on patient-reported outcomes and the relationship between concomitant use of antidepressants and remission in patients with depression.Design:Data from patients with moderate to severe RA were pooled from five randomised controlled trials investigating tocilizumab and conventional synthetic disease-modifying agents.Methods:Remission was defined as a clinical disease activity index (CDAI) of ⩽2.8 and simple disease activity index (SDAI) of ⩽3.3. The association between the time to reach remission and depression and anxiety was analysed using Cox proportional hazard analysis.Results:Individual patient data were available from 5502 subjects, of whom 511 had depression, 236 had anxiety and 387 were using antidepressants. Depression was significantly associated with reduced remission [adjusted HR (95% CI): 0.62 (0.48–0.80), p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-22T12:07:28Z
      DOI: 10.1177/1759720X221111613
      Issue No: Vol. 14 (2022)
       
  • A glance into the future of diagnosis and treatment of spondyloarthritis

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      Authors: Victoria Navarro-Compán, Joerg Ermann, Denis Poddubnyy
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      The last two decades have seen major developments in the field of spondyloarthritis (SpA), but there are still important unmet needs to address. In the future, we envisage important advances in the diagnosis and treatment of SpA. In the diagnosis of SpA, the use of online and social media tools will increase awareness of the disease and facilitate the referral of patients to rheumatology clinics. In addition, more specific diagnostic tests will be available, especially advanced imaging methods and new biomarkers. This will allow most patients to be diagnosed at an early stage of the disease. In the treatment of SpA, an increasing number of novel treatment targets can be expected, most of which will be directed against intracellular enzymes. We hope to see more strategy trials shaping treatment pathways in SpA and accommodating principals of precision medicine. Approved treatment options will be available for both axial and peripheral SpA. We also hope to intervene not only at the inflammation level but also at the level of underlying immunological processes that might be associated with a higher probability of long-standing remission if not a cure. Finally, artificial intelligence techniques will allow for the analysis of large-scale data to answer relevant research questions for the diagnosis and management of patients with SpA.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-22T12:05:08Z
      DOI: 10.1177/1759720X221111611
      Issue No: Vol. 14 (2022)
       
  • Changes in ultrasound imaging of joints, entheses, bursae and tendons 24
           and 48 h after adjusted weight training

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      Authors: Julia K. Schreiner, Florian Recker, Dennis Scheicht, Pantelis Karakostas, Jana Ziob, Charlotte Behning, Peter Preuss, Peter Brossart, Valentin S. Schäfer
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Joint effusion and enthesitis are common ultrasound findings in rheumatic diseases such as rheumatoid arthritis or spondyloarthritis. However, changes of joints and entheses were not only observed in patients but also in physically active individuals and athletes.Objectives:The purpose of this study was to evaluate joint, entheseal, bursal and tendon musculoskeletal ultrasound (MSUS) findings in large and medium joints of young healthy individuals after completing a standardised weight training.Design:This is a prospective cohort study.Methods:MSUS examinations of large- and medium-sized joints, and related entheseal sites, bursae and tendons were performed on young healthy individuals (ages 18–30 years). Before, 24 and 48 h after completing 1 h of standardised weight exercise, the subjects were evaluated by MSUS. The development of the MSUS findings and associated effects were examined using generalised linear mixed effects models.Results:In total, 51 healthy individuals (52.9% female) with a mean age of 23.7 (±2.5) years were enrolled. The results showed an increase in the number of individuals with at least one joint effusion from 37 (72.5%) before the weight training to 48 (94.1%) after 48 h. Entheses with pathologies were observed in 14 participants (27.5%) at baseline, increasing to 29 participants (56.9%) 48 h after the weight training. Biceps tendon sheath effusion was detected in 9 individuals (17.6%) prior to training, rising to 22 individuals (43.1%) after 48 h. A significant increase in the number of joints with effusion and abnormal entheses within 48 h after the weight training was indicated by the generalised linear mixed effects models.Conclusion:Within 48 h after the weight training session, a significant increase in the prevalence of joint effusion in large and medium joints and the prevalence of abnormal entheses was observed. As a result, when performing and interpreting an MSUS examination, the patient’s physical activities should be taken into account.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-22T12:02:30Z
      DOI: 10.1177/1759720X221111610
      Issue No: Vol. 14 (2022)
       
  • Predicting osteoarthritis in adults using statistical data mining and
           machine learning

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      Authors: Carlo M. Bertoncelli, Paola Altamura, Sikha Bagui, Subhash Bagui, Edgar Ramos Vieira, Stefania Costantini, Marco Monticone, Federico Solla, Domenico Bertoncelli
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Osteoarthritis (OA) has traditionally been considered a disease of older adults (⩾65 years old), but it may appear in younger adults. However, the risk factors for OA in younger adults need to be further evaluated.Objectives:To develop a prediction model for identifying risk factors of OA in subjects aged 20–50 years and compare the performance of different machine learning models.Methods:We included data from 52,512 participants of the National Health and Nutrition Examination Survey; of those, we analyzed only subjects aged 20–50 years (n = 19,133), with or without OA. The supervised machine learning model ‘Deep PredictMed’ based on logistic regression, deep neural network (DNN), and support vector machine was used for identifying demographic and personal characteristics that are associated with OA. Finally, we compared the performance of the different models.Results:Being a female (p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-16T08:54:25Z
      DOI: 10.1177/1759720X221104935
      Issue No: Vol. 14 (2022)
       
  • Concentric or eccentric physical activity for patients with symptomatic
           osteoarthritis of the knee: a randomized prospective study

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      Authors: Marie-Charlotte Trojani, Fréderic Chorin, Pauline Gerus, Véronique Breuil, Constance Michel, Sandrine Guis, David Bendahan, Christian Roux
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Knee osteoarthritis–related pain limits physical function and leads to functional disability. Physical activity is one of the central recommendations for the management of knee osteoarthritis. Although concentric muscle activities are often preferred to eccentric ones, the corresponding rationale remains controversial.Objective:To explore the effect of a 6-week exercise program on function, pain, and performance in patients with symptomatic knee osteoarthritis.Methods:Patients with symptomatic knee osteoarthritis were included in the prospective EX-ART project (Walking performance in osteoARThritic subjects: effect of an ECCentric muscle strengthening program) and randomized in a 6-week rehabilitation program including either eccentric or concentric activities. Metrics of interest chosen as end points measured before and after the rehabilitation were WOMAC score, pain, and muscular performance (quadriceps power PMAX and contraction strength MMAX). MRI was also used to assess muscle volume and fat infiltration changes.Results:30 patients were included in each group; mean age was 74 (±7.6); 69% were women. At week 6, both groups showed a significant improvement in the WOMAC without difference between the two groups (p = 0.7). No difference between the two groups was identified for the pain reduction (p = 0.7). A significant improvement in the change in PMAX and MMAX at high velocity (p = 0.001 and p = 0.002) was observed in the eccentric group only. A vastus medialis hypertrophy was quantified in the eccentric group only (p = 0.002), whereas fat infiltration in the quadriceps muscles was unchanged.Conclusion:Physical activity, whether eccentric or concentric, has a benefit on function and pain in patients with symptomatic knee osteoarthritis. A few differences have been identified between the two types of rehabilitation. More particularly, a gain in muscle performance and vastus medialis volume was found with eccentric rehabilitation only.Registration:www.ClinicalTrials.gov, registration number NCT03167502.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-07T12:44:10Z
      DOI: 10.1177/1759720X221102805
      Issue No: Vol. 14 (2022)
       
  • Back pain treatment: a new perspective

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      Authors: Anke Steinmetz
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      This article aims to provide new perspectives for the treatment of low back pain (LBP). A narrative literature review highlights the treatment strategies currently anchored in the guidelines as well as the extensive attempts to identify subgroups within the non-specific low back pain (NSLBP) classification. A variety of multimodal approaches exist for both diagnostic assessments and therapy approaches. Nonetheless, there are often gaps in the classification systems as well as in published treatment concepts with regard to the implementation of musculoskeletal functional disorders. Indeed, a growing body of evidence shows that more holistic and flexible approaches are needed to individually diagnose and target the complexity of LBP. As an example, both a diagnostic and a (independently developed) therapeutic LBP concept will be presented and discussed. Ultimately, guidelines and subgroup classification systems can only reflect the complexity of LBP, if they capture its entire multidimensional and biopsychosocial character in both the diagnostic and therapeutic processes. Furthermore, the expansion of the pain definition to include the nociplastic pain mechanism, as an important driver of LBP, has the potential to provide important impulses for further necessary research. In conclusion, the implementation of a functional musculoskeletal approach along with the emerging nociceptive pain concept in individually targeted holistic approaches seems to be the successful way to deal with the complexity of LBP.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-05T06:23:13Z
      DOI: 10.1177/1759720X221100293
      Issue No: Vol. 14 (2022)
       
  • Zoledronic acid does not slow spinal radiographic progression of
           osteoarthritis in postmenopausal women with osteoporosis and radiographic
           osteoarthritis

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      Authors: L.V. Host, H.I. Keen, L.L. Laslett, D.M. Black, G. Jones
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:Post hoc analyses of osteoporosis trials have suggested that alendronate and strontium ranelate may be associated with a reduction in the progression of spinal radiographic osteoarthritis (OA). We performed an analysis on a subgroup of participants in the horizon PFT trial (a 3-year randomized controlled trial (RCT) of yearly zoledronic acid (ZA) in postmenopausal women with osteoporosis), to evaluate the effect of ZA on the structural progression of spinal osteophytes (OPh) and disk space narrowing (DN).Methods:Paired lateral spinal X-rays (baseline and 36 months) were selected from the horizon PFT trial records restricted to those with radiographic OA at baseline. The X-rays were analyzed by two readers blinded to the treatment allocation. OPh and DN were scored separately using the Lane atlas (0–3 for increasing severity at each vertebral level) at all evaluable levels from T4–12 and L1–5.Results:A total of 504 sets of paired radiographs were included in the analysis, 245 in the ZA group and 259 in the placebo group. Overall, the rates of change of OPh and DN scores were low, and they were not statistically different between the groups (change in the whole spine OPh ZA 1.0 ± 1.6, placebo 0.8 ± 1.3, p = 0.1; DN ZA 0.3 ± 1.0, placebo 0.3 ± 0.8, p = 0.7).Conclusion:Yearly ZA for 3 years was not associated with a slowing of progression of OPh or DN in the thoracolumbar spine in patients with pre-existing radiographic OA.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-07-05T06:20:41Z
      DOI: 10.1177/1759720X221081652
      Issue No: Vol. 14 (2022)
       
  • Big data analyses and individual health profiling in the arena of
           rheumatic and musculoskeletal diseases (RMDs)

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      Authors: Diederik De Cock, Elena Myasoedova, Daniel Aletaha, Paul Studenic
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Health care processes are under constant development and will need to embrace advances in technology and health science aiming to provide optimal care. Considering the perspective of increasing treatment options for people with rheumatic and musculoskeletal diseases, but in many cases not reaching all treatment targets that matter to patients, care systems bare potential to improve on a holistic level. This review provides an overview of systems and technologies under evaluation over the past years that show potential to impact diagnosis and treatment of rheumatic diseases in about 10 years from now. We summarize initiatives and studies from the field of electronic health records, biobanking, remote monitoring, and artificial intelligence. The combination and implementation of these opportunities in daily clinical care will be key for a new era in care of our patients. This aims to inform rheumatologists and healthcare providers concerned with chronic inflammatory musculoskeletal conditions about current important and promising developments in science that might substantially impact the management processes of rheumatic diseases in the 2030s.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-06-30T10:16:48Z
      DOI: 10.1177/1759720X221105978
      Issue No: Vol. 14 (2022)
       
  • Racial and ethnic differences in the pharmacologic management of
           osteoarthritis: rapid systematic review

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      Authors: Ernest R. Vina, Philip H. Tsoukas, Shahrzad Abdollahi, Nidhi Mody, Stephanie C. Roth, Albert H. Redford, C. Kent Kwoh
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Racial and ethnic disparities in osteoarthritis (OA) patients’ disease experience may be related to marked differences in the utilization and prescription of pharmacologic treatments.Objectives:The main objective of this rapid systematic review was to evaluate studies that examined race/ethnic differences in the use of pharmacologic treatments for OA.Data sources and methods:A literature search (PubMed and Embase) was ran on 25 February 2022. Studies that evaluated race/ethnic differences in the use of OA pharmacologic treatments were included. Two reviewers independently screened titles and abstracts and abstracted data from full-text articles. Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.Results:The search yielded 3880 titles, and 17 studies were included in this review. African Americans and Hispanics were more likely than non-Hispanic Whites to use prescription non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for OA. However, compared to non-Hispanic Whites with OA, African Americans and Hispanics with OA were less likely to receive a prescription for cyclooxygenase-2-selective NSAIDs and less likely to report the use of joint health supplements (i.e. glucosamine and chondroitin sulfate). There were minimal/no significant race/ethnic differences in the patient-reported use of the following OA therapies: acetaminophen, opioids, and other complementary/alternative medicines (vitamins, minerals, and herbs). There were also no significant race differences in the receipt of intra-articular therapies (i.e. glucocorticoid or hyaluronic acid). However, there is limited evidence to suggest that African Americans may be less likely than Whites to receive opioids and intra-articular therapies in some OA patient populations.Conclusion:This systematic review provides an overview of the current pharmacologic options for OA, with a focus on race and ethnic differences in the use of such medical therapies.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-06-30T10:13:33Z
      DOI: 10.1177/1759720X221105011
      Issue No: Vol. 14 (2022)
       
  • Real-life short-term effectiveness of anti-osteoporotic treatments: a
           longitudinal cohort study

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      Authors: Giovanni Adami, Irene Gavioli, Maurizio Rossini, Ombretta Viapiana, Giovanni Orsolini, Camilla Benini, Eugenia Bertoldo, Elena Fracassi, Davide Gatti, Angelo Fassio
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:Randomized clinical trials have shown that anti-osteoporotic treatments can increase bone mineral density (BMD) and reduce the incidence of fragility fractures. However, data on the real-life effectiveness of anti-osteoporotic medications are still scarce.Methods:We conducted a cohort study on women at high risk of fracture. We retrieved clinical and densitometric data from the DeFRA database, which derives from the DeFRA tool, a web-based fracture risk assessment tool. Multivariable Cox regression survival models were employed to analyze the effectiveness of different anti-osteoporotic drugs on fracture. In sensitivity analyses, we conducted 1:1 propensity score matching analyses.Results:Data on 50,862 women were available. Among these, 3574 individuals had at least two consecutive visits. The crude fracture rate was 91.9/1000 person-year for non-treated patients. The crude fracture rate in bisphosphonate users was 72.1/1000 person-year, in denosumab users was 58.2/1000 person-year, and in teriparatide users was 19.3/1000 person-year. Overall, we found that bisphosphonate use was associated with a 30% lower risk of fracture compared to no treatment [adjusted hazard ratio (aHR): 0.70, 95% confidence interval (CI): 0.50–0.98]. Treatment with denosumab and teriparatide were associated with 60% and 90% lower risk of fracture, respectively (aHR: 0.43, 95% CI: 0.24–0.75 and aHR: 0.09, 95% CI: 0.01–0.70). Bisphosphonate use was associated with a lower risk of fracture only after 1 year of treatment.Conclusion:In conclusion, we found that all anti-osteoporotic medications considered in the study effectively reduced the risk of fracture in the real-life. The effect of bisphosphonate on fracture risk was apparent only after the first year of treatment. Our findings do not support the use of bisphosphonates in patients at imminent risk of fracture.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-06-27T10:00:46Z
      DOI: 10.1177/1759720X221105009
      Issue No: Vol. 14 (2022)
       
  • Gout increases length of stay in patients hospitalized for heart failure
           exacerbation

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      Authors: Daniel DeMizio, Guojing Wu, Ying Wei, Joan Bathon, Runsheng Wang
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:It is unclear whether patients with a history of gout have longer hospitalizations in general, or only when suffering a flare. This study examines the effect of gout diagnosis and gout flare on the length of stay (LoS) in patients admitted for heart failure (HF) exacerbation.Methods:We conducted a matched retrospective cohort study and searched electronic medical records for patients admitted for HF with a prior diagnosis of gout from 1 July 2012 to 30 June 2017 and matched them to patients admitted for HF without gout. Cases who had a gout flare during the admission were identified. The log of the length of stay (log LoS) was utilized for normalization of the data. We used a linear mixed-effect model to compare the adjusted LoS of gout patient with flare, gout patient without flare, and controls.Results:A total of 978 admissions for HF exacerbation in 738 patients, including 246 individual with gout and 492 matched controls, were identified and included in the analysis. The log LoS was significantly longer in cases (1.86 ± 0.95) compared with controls (1.72 ± 0.94; p = 0.0278). The log LoS was significantly longer in those with gout who flared (2.41 ± 0.96) compared to those without gout (1.72 ± 0.94, p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-06-14T09:53:46Z
      DOI: 10.1177/1759720X221102853
      Issue No: Vol. 14 (2022)
       
  • Real-world evidence to assess the effectiveness of platelet-rich plasma in
           the treatment of knee degenerative pathology: a prospective observational
           study

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      Authors: Mikel Sánchez, Cristina Jorquera, Leonor López de Dicastillo, Nicolás Fiz, Jorge Knörr, Maider Beitia, Beatriz Aizpurua, Juan Azofra, Diego Delgado
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objective:The present work aims to analyse the effectiveness of platelet-rich plasma (PRP) in degenerative knee pathology based on real-world data and to evaluate possible factors influencing the response to treatment.Methods:In total, 531 cases were analysed collecting data on gender, age, body mass index, pathology location, severity, number of cycles and route of administration. Clinical outcome was evaluated at 6 and 15 months after treatment, using the Knee injury and Osteoarthritis Outcome Score (KOOS) and obtaining percentages of Minimal Clinically Important Improvement (MCII). Blood and PRP samples were randomly tested as a quality control measure to ensure the correct properties. Comparative statistical tests and multivariate regression were performed for the analysis of the variables.Results:The PRP applied had a platelet concentration factor of 1.67, with no leukocytes or erythrocytes. The percentage of patients with MCII at 6 and 15 months after PRP application was 59.32% and 70.62%, respectively. Patients with MCII were younger (p = 0.0246) and with lower body mass index (p = 0.0450). The treatment had a better response in mild/moderate cases than in severe cases (p = 0.0002). Intraosseous PRP application in severe cases improved the effect of intraarticular PRP (p = 0.0358). The application of a second cycle of PRP only improved the response in patients without MCII at 6 months (p = 0.0029), especially in mild/moderate cases (p = 0.0357).Conclusion:The applications of PRP in degenerative knee pathologies is an effective treatment, but this effectiveness nonetheless depends on several variables. Real-world data can complement that from clinical trials to provide valuable information.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-06-14T08:50:24Z
      DOI: 10.1177/1759720X221100304
      Issue No: Vol. 14 (2022)
       
  • SARS-CoV-2 vaccination willingness and predictors in patients with chronic
           inflammatory rheumatic diseases (CIRD) and without CIRD

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      Authors: Iulia Roman, Ioana Andreica, Xenofon Baraliakos, Imke Redeker, Uta Kiltz, Jürgen Braun
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Recent surveys in chronic inflammatory rheumatic diseases (CIRD) showed a high degree of vaccine hesitancy. Current knowledge about patients’ attitudes toward vaccination against SARS-CoV-2 is limited.Objectives:To assess the willingness of CIRD patients to be vaccinated against SARS-CoV-2 and to identify the influencing factors compared with non-CIRD patients.Methods:In this cross-sectional study, two cohorts of consecutive patients with and without CIRD were recruited in parallel when presenting to our tertiary hospital and asked to answer questions of a structured interview to assess vaccination willingness to SARS-CoV-2 their experience with SARS-CoV-2 and their personal history of infections and vaccinations. Vaccination willingness was assessed using a numerical rating scale (0: fully disagree; 10: fully agree). Arbitrarily defined cut-offs were used to define definite (score ⩾7) and probable willingness (score of 5 or 6) to be vaccinated. Factors associated with willingness were assessed using Kendall’s tau-b correlation measure and linear regression analysis.Results:A total of 514 CIRD and 100 non-CIRD patients, mean age of 54.7 ± 12.8 and 55.6 ± 9.8 years, respectively, were included. Definite and probable willingness to be vaccinated against SARS-CoV-2 was declared by 79.6% and 90.7% versus 76.0% and 85.0% of CIRD and non-CIRD patients, respectively. Only 60% of CIRD patients believed that the vaccines against SARS-CoV-2 were safe, and 42% indicated to be afraid of side effects. Vaccination willingness was significantly correlated with being in a risk group for COVID-19 (tau-b = −0.149), hypertension (tau-b = 0.14), and information about disease prevention (tau-b = 0.19), while a history of infections or immunosuppressive therapy was not. Vaccination willingness was significantly associated with higher education (b = 0.65) and age (b = 0.06).Conclusion:This survey highlights several predictors of relevance for the vaccination willingness of patients with CIRD and controls including appropriate information about its relevance. The good news, however, is that the vast majority of CIRD patients indicated their willingness to be vaccinated. However, there was some uncertainty regarding the safety and efficacy of the vaccines. Since the major influencing factors were education and information about SARS-CoV-2 Vaccine and COVID-19 Disease, patient education should be improved soon.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-06-10T12:16:03Z
      DOI: 10.1177/1759720X221093760
      Issue No: Vol. 14 (2022)
       
  • Validation of the 2019 EULAR/ACR classification criteria for systemic
           lupus erythematosus in ANA-positive Chinese patients

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      Authors: Yuen Kwan Chung, Ling Yin Ho, Carolyn Lee, Chi Hung To, Chi Chiu Mok
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:The aim of this study was to validate the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) in antinuclear antibody (ANA)-positive Chinese patients.Methods:Medical records of all adult patients who attended the rheumatology out-patient clinics between May and September 2019 were reviewed. Patients with ever ANA positive (titre ⩾1:80) were included and evaluated for the fulfilment of the 2019 EULAR/ACR, 2012 Systemic Lupus International Collaborating Clinics (SLICC) and 1997 ACR criteria for SLE classification. The performance of these criteria in predicting a clinical diagnosis of SLE as judged by an independent panel of rheumatologists was studied and compared in different subgroups.Results:A total of 1533 patients (88.2% women; age at first clinic attendance 45.5 ± 15.6 years) were studied and 562 patients were judged to be clinical SLE. The sensitivity and specificity of the EULAR/ACR (⩾10 points), SLICC and ACR criteria for a clinical diagnosis of SLE was 96.1%, 97.9% and 86.1%; and 85.8%, 86.3% and 94.3%, respectively. Applying the attribution rule to the non-SLE controls, the specificity of the three criteria increased to 95.0%, 92.5% and 98.8%, respectively. The specificity of the EULAR/ACR criteria was higher in male patients (97.9%), those aged>50 years (97.0%) and disease duration of ⩽3 years (97.6%). Using a cut-off of 12 points, the specificity of the EULAR/ACR criteria was further increased (96.6%) while a high sensitivity (95.0%) was maintained.Conclusion:In Chinese patients with a positive ANA, the EULAR/ACR criteria for clinical SLE perform equally well to the SLICC criteria. Both the EULAR/ACR and SLICC are more sensitive but less specific than the ACR criteria. The specificity of all the three criteria is enhanced by applying the attribution rule to controls. The specificity of the EULAR/ACR criteria is higher in certain patient subgroups or when the cut-off score is raised.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-28T05:17:26Z
      DOI: 10.1177/1759720X221100300
      Issue No: Vol. 14 (2022)
       
  • A glance into the future of myositis therapy

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      Authors: Ilaria Chiapparoli, Claudio Galluzzo, Carlo Salvarani, Nicolò Pipitone
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      The idiopathic inflammatory myopathies are chronic diseases of the skeletal muscle that comprise various conditions, including dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and the antisynthetase syndrome. Although there are a number of distinguishing features, all these disorders are characterized by an immune and inflammatory response mainly directed against the muscle. Hence, therapy is geared toward curbing the autoimmune and inflammatory response. A quite wide range of medications are currently available to treat these disorders, but despite all therapeutic progress still a number of patients are unable to maintain a sustained remission. In this review article, we have marshaled a variety of potential therapeutic agents that may hold promise for the future treatment of the idiopathic inflammatory myopathies. It is to be expected that by increasing the therapeutic armamentarium with agents that have different mechanisms of action even challenging cases could be successfully managed, thus reducing disease burden and disability.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-25T06:08:13Z
      DOI: 10.1177/1759720X221100299
      Issue No: Vol. 14 (2022)
       
  • Looking ahead: giant-cell arteritis in 10 years time

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      Authors: Milena Bond, Alessandro Tomelleri, Frank Buttgereit, Eric L. Matteson, Christian Dejaco
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Although great improvements have been achieved in the fields of diagnosing and treating patients with giant-cell arteritis (GCA) in the last decades, several questions remain unanswered. The progressive increase in the number of older people, together with growing awareness of the disease and use of advanced diagnostic tools by healthcare professionals, foretells a possible increase in both prevalence and number of newly diagnosed patients with GCA in the coming years. A thorough clarification of pathogenetic mechanisms and a better definition of clinical subsets are the first steps toward a better understanding of the disease and, subsequently, toward a better use of existing and future therapeutic options. Examination of the role of different imaging techniques for GCA diagnosing and monitoring, optimization, and personalization of glucocorticoids and other immunosuppressive agents, further development and introduction of novel drugs, identification of prognostic factors for long-term outcomes and management of treatment discontinuation will be the central topics of the research agenda in years to come.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-25T06:06:12Z
      DOI: 10.1177/1759720X221096366
      Issue No: Vol. 14 (2022)
       
  • Age-stratified trends in the progression of spinal radiographic damage in
           patients with ankylosing spondylitis: a longitudinal study

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      Authors: Tae-Han Lee, Bon San Koo, Bora Nam, Yun Jin Kim, Donghee Son, Seunghun Lee, Kyung Bin Joo, Tae-Hwan Kim
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objective:The objective of this study was to investigate spinal radiographic progression in specific age ranges of ankylosing spondylitis (AS) patients.Methods:Longitudinal data for 1125 AS patients at a single hospital from 2000 to 2018 were retrospectively reviewed. Radiographic intervals were obtained from patients with consecutive spinal radiographs. The radiographic progression rate was defined as the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change per year within each interval. Using generalized estimating equations (GEEs), estimated marginal means were calculated for the mSASSS progression rate across age groups after adjusting for potential confounders.Results:We obtained 4016 radiographic intervals and stratified them into five groups based on patient age at the interval start:
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-23T10:51:01Z
      DOI: 10.1177/1759720X221100301
      Issue No: Vol. 14 (2022)
       
  • Sjögren syndrome: looking forward to the future

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      Authors: Sara Zandonella Callegher, Ivan Giovannini, Sabine Zenz, Valeria Manfrè, Martin H. Stradner, Alojzija Hocevar, Marwin Gutierrez, Luca Quartuccio, Salvatore De Vita, Alen Zabotti
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Primary Sjögren’s syndrome (pSS) is a heterogeneous disease characterised by a wide spectrum of manifestations that vary according to the different stages of the disease and among different subsets of patients. The aim of this qualitative literature review is to summarise the recent advances that have been reported in pSS, ranging from the early phases to the established disease and its complications. We analysed the diagnostic, prognostic, and management aspects of pSS, with a look into future clinical and research developments. The early phases of pSS, usually antedating diagnosis, allow us to investigate the pathophysiology and risk factors of the overt disease, thus allowing better and timely patient stratification. Salivary gland ultrasound (SGUS) is emerging as a valid complementary, or even alternative, tool for histopathology in the diagnosis of pSS, due to a standardised scoring system with good agreement and performance. Other promising innovations include the application of artificial intelligence to SGUS, ultrasound-guided core needle biopsy, and a wide array of novel diagnostic and prognostic biomarkers. Stratifying pSS patients through the integration of clinical, laboratory, imaging, and histopathological data; differentiating between activity-related and damage-related manifestations; and identifying patients at higher risk of lymphoma development are essential steps for an optimal management and individualised treatment approach. As new treatment options are emerging for both glandular and systemic manifestations, there is a need for a more reliable treatment response evaluation. pSS is a complex and heterogeneous disease, and many distinct aspects should be considered in the different stages of the disease and subsets of patients. In recent years, efforts have been made to improve our understanding of the disease, and certainly in the coming years, some of these novelties will become part of our routine clinical practice, thus improving the management of pSS patients.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-23T10:48:42Z
      DOI: 10.1177/1759720X221100295
      Issue No: Vol. 14 (2022)
       
  • Cell-based therapies for rheumatoid arthritis: opportunities and
           challenges

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      Authors: Yu-Jing Li, Zhu Chen
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Rheumatoid arthritis (RA) is the most common immune-mediated inflammatory disease characterized by chronic synovitis that hardly resolves spontaneously. The current treatment of RA consists of nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic and targeted synthetic DMARDs. Although the treat-to-target strategy has been intensively applied in the past decade, clinical unmet needs still exist since a substantial proportion of patients are refractory or even develop severe adverse effects to current therapies. In recent years, with the deeper understanding of immunopathogenesis of the disease, cell-based therapies have exhibited effective and promising interventions to RA. Several cell-based therapies, such as mesenchymal stem cells (MSC), adoptive transfer of regulatory T cells (Treg), and chimeric antigen receptor (CAR)-T cell therapy as well as their beneficial effects have been documented and verified so far. In this review, we summarize the current evidence and discuss the prospect as well as challenges for these three types of cellular therapies in RA.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-23T10:45:54Z
      DOI: 10.1177/1759720X221100294
      Issue No: Vol. 14 (2022)
       
  • Repurposed and investigational disease-modifying drugs in osteoarthritis
           (DMOADs)

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      Authors: Win Min Oo, David J. Hunter
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      In spite of a major public health burden with increasing prevalence, current osteoarthritis (OA) management is largely palliative with an unmet need for effective treatment. Both industry and academic researchers have invested a vast amount of time and financial expense to discover the first diseasing-modifying osteoarthritis drugs (DMOADs), with no regulatory success so far. In this narrative review, we discuss repurposed drugs as well as investigational agents which have progressed into phase II and III clinical trials based on three principal endotypes: bone-driven, synovitis-driven and cartilage-driven. Then, we will briefly describe the recent failures and lessons learned, promising findings from predefined post hoc analyses and insights gained, novel methodologies to enhance future success and steps underway to overcome regulatory hurdles.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-20T10:55:51Z
      DOI: 10.1177/1759720X221090297
      Issue No: Vol. 14 (2022)
       
  • Calcineurin inhibitors in systemic sclerosis – a systematic
           literature review

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      Authors: Nina N. Hofmann, Robert A. Ambühl, Suzana Jordan, Oliver Distler
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objective:To review treatment effectiveness and adverse events of calcineurin inhibitors (CNIs) such as cyclosporin A (CsA) and tacrolimus in patients with systemic sclerosis (SSc).Methods:A systematic literature search was performed on PubMed and Web of Science using the predefined keywords ‘systemic sclerosis’, scleroderma, cyclosporin*, and tacrolimus. Articles were eligible for inclusion, if SSc patients had been treated with CNIs and data on treatment effects were available.Results:This systematic literature review identified 37 papers (19 case reports, 15 case series, 2 controlled studies, and 1 retrospective study) including 134 SSc patients treated with CNIs. In 34 of 37 papers, CsA was used. An improvement of skin fibrosis was observed in 77 of 96 (80.2%) patients using a wide variety of outcome measures and dose regimes. Both controlled studies showed significant improvements, one using a historical control group and one using a no-treatment control group. Improvement in pulmonary function tests (PFTs) occurred in 67.9% (19/28) of the patients who had reduced PFTs at baseline. In 58 (43.3%) cases, adverse renal events were reported, of which 7 (5.2%) were severe such as scleroderma renal crisis (SRC), CsA-associated nephropathy, or death by renal insufficiency. Adverse events led to dose reduction, treatment interruption, or withdrawal in 39 of 134 (29.1%).Conclusion:In this systematic literature review, signals for potential effectiveness of CsA for skin and pulmonary fibrosis were found, but the evidence level of the identified studies was too low to allow robust conclusions. Randomized controlled double-blind trials are needed to conclude on the effectiveness of CNIs in SSc. Renal toxicity of CNIs was confirmed in this review and needs to be considered in the design of such studies.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-19T12:52:48Z
      DOI: 10.1177/1759720X221092374
      Issue No: Vol. 14 (2022)
       
  • Ultrasound-detected inflammation is more common in clinically manifest
           hand osteoarthritis than in painless bony enlarged finger joints:
           subanalysis of the population-based Bruneck study

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      Authors: Nina Gasperi, Nikolaus Schreiber, Philipp Bosch, Antonella Adinolfi, Arnd Kleyer, Melanie Hagen, Christiane Gasperi, Martin Weger, Stefan Kiechl, Johann Willeit, Georg Schett, Annamaria Iagnocco, Arno Gasperi, Agnes Mayr, Christian Dejaco
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Purpose:The aim of this article is to examine the extent of structural and inflammatory lesions by ultrasound in elderly subjects with hand osteoarthritis (HOA) fulfilling the ACR classification criteria (Group A), in subjects with painless enlarged finger joints (Group B), and in individuals without clinical abnormalities at hands (Group C).Methods:This study was nested within the population-based, prospective Bruneck study; 293 subjects of ⩾65 years of age were assessed. Clinical and ultrasound assessment was conducted at wrists and finger joints. Gray scale synovitis (GSS), Power Doppler (PD), osteophytes, and erosions were scored semiquantitatively (0–3). The Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH), the Health Assessment Questionnaire (HAQ), and the Functional Index for Hand Osteoarthritis (FIHOA) were retrieved.Results:Most subjects had ⩾1 ultrasound abnormality, of which osteophytes were the most prevalent finding in all groups (Group A: 100%, Group B: 99.4%, and Group C: 93.9%). GSS and PD-signals were more common in Group A than in Group B (94% versus 67% and 33% versus 13%, respectively). In Group C, GSS was observed in 39.4% of subjects. In subjects with HOA, the SF-SACRAH correlated with osteophyte scores (corrcoeff = 0.48), and the FIHOA correlated with the osteophyte (corrcoeff = 0.42) and PD scores (corrcoeff = 0.33).Conclusion:GSS and PD were more frequent in patients with symptomatic HOA than in cases with painless bony enlargements and subjects without clinical joint abnormalities. Functional restriction in HOA is associated with structural and inflammatory ultrasound changes.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-14T07:17:56Z
      DOI: 10.1177/1759720X221096382
      Issue No: Vol. 14 (2022)
       
  • Gout management and outcomes during established COVID-19 pandemic in
           2020–2021: a cross-sectional Internet survey

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      Authors: Jasvinder A. Singh, N. Lawrence Edwards
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objective:To assess the management of gout in established COVID-19 pandemic.Methods:We assessed medication use, health care utilization, gout-specific health-related quality of life (HRQOL), psychological distress using Patient Health Questionnaire–4 (PHQ-4), resilience, illness perception, and health literacy in people with physician-diagnosed self-reported gout in established COVID-19 pandemic in a cross-sectional Internet survey.Results:Among the 130 survey respondents with gout, the mean age was 62.8 years, 65% were male, 83% were White, 59% were prescribed urate-lowering therapy (ULT), and health literacy was adequate in 80%. A third of survey respondents reported more difficulty with their gout management since September 2020. Gout-specific HRQOL deficits were evident. Moderate-severe psychological distress was seen in 22%, and resilience score was 6.5 [standard deviation (SD), 1.9; range, 0–8]. Adjusted for age and sex, compared with no/mild psychological distress, moderate-severe psychological distress was associated with significantly higher odds ratio (OR; 95% confidence interval) of more difficulty with (1) getting health care for gout in clinic, 3.7 (1.0, 13.2); emergency room/urgent care, 8.1 (1.4, 45.0); and in the hospital, 9.8 (1.6, 59.6); (2) getting gout flares treated, 6.6 (1.6, 26.8); (3) avoiding gout complications, 4.5 (1.2, 16.7); and (4) daily activities at home, 4.2 (1.3, 14.1), and performing work, 4.1 (1.2, 13.6).Conclusion:Respondents with gout reported health care gaps, low rates of ULT prescription, high psychological distress, and HRQOL deficits during established COVID-19 pandemic. Moderate-severe psychological distress was associated with difficulties in health care access and gout management. Interventions to address these challenges in gout management are needed.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-13T08:55:10Z
      DOI: 10.1177/1759720X221096381
      Issue No: Vol. 14 (2022)
       
  • Comparative efficacy and safety of mizoribine and mycophenolate mofetil
           for treating systemic lupus erythematosus: a retrospective cohort study

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      Authors: Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Nobuyuki Ono, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Mizoribine (MZR) is an immunosuppressive agent that selectively inhibits inosine monophosphate dehydrogenase; its actions are considerably similar to those of mycophenolate mofetil (MMF). This study aimed to clarify whether MZR can be a good treatment option for systemic lupus erythematosus (SLE) and to compare the efficacy and safety of MZR and MMF in patients with active SLE.Methods:We retrospectively compared the efficacy, continuation rate, and safety of MZR (52 patients) and MMF (31 patients) after adjusting for stabilized inverse probability of treatment weighting based on propensity scores. The efficacy endpoints were as follows: cumulative incidence of lupus low disease activity state (LLDAS) or remission attainment and flares and change in prednisolone dose over 2 years. Drug continuation rates were defined as the time from drug initiation to discontinuation for any cause, owing to the lack of efficacy, or owing to adverse events. The safety endpoint was the frequency of adverse events.Results:Overall, 25 (48.1%) and 13 (25.0%) patients in the MZR group and 18 (58.1%) and 15 (48.3%) in the MMF group achieved LLDAS and remission during the follow-up period, respectively; thus, the cumulative incidence of LLDAS and remission attainment of the two groups was similar after adjustment. Prednisolone dose was steadily reduced in both the groups, and the change in prednisolone dose was nearly identical between the two groups. Drug discontinuation rate due to adverse events and the frequency of all adverse events and infections were higher in the MMF group than in the MZR group, albeit without significance after adjustment.Conclusion:MZR is as effective as MMF in controlling SLE activity. The adverse events of MZR, whose profile differs from MMF, are comparable to or less than those of MMF. MZR may be a valuable option as an immunosuppressive agent for SLE, as well as MMF.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-13T08:53:30Z
      DOI: 10.1177/1759720X221096367
      Issue No: Vol. 14 (2022)
       
  • Comparison of remission criteria in patients with rheumatoid arthritis
           treated with biologic or targeted synthetic disease-modifying
           anti-rheumatic drugs: results from a nationwide registry

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      Authors: Jung Hee Koh, Yusun Lee, Hyoun-Ah Kim, Jinhyun Kim, Kichul Shin
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) are widely used for treatment of rheumatoid arthritis (RA), enabling patients to better achieve remission.Objective:The objective of the study was to investigate and compare remission rates in RA patients treated with different b/tsDMARDs during the period 2013–2019.Design:A longitudinal observational analysis was performed on data from a nationwide RA registry.Methods:Remission rates in the KOBIO-RA registry were defined by a disease activity score in 28 joints (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI), and Boolean-based assessment. After initiating treatment with b/tsDMARDs, yearly remission rates in response to b/tsDMARDs, either all or as subgroups (tumor necrosis factor-α inhibitors, tocilizumab, abatacept, and Janus kinase inhibitors), were investigated for 5 years. Sustained remission was defined as remission maintained for two consecutive years.Results:Patients (N = 1805) who completed at least one follow-up visit were analyzed (mean age = 55 years; 83.2% female). At month 12, 56.0% of patients achieved remission based on DAS28-C-reactive protein (CRP), 36.2% on DAS28-erythrocyte sedimentation rate (ESR), 10.4% on CDAI, 12.7% on SDAI, and 12.9% on Boolean criteria. Sustained remission rates were 62%, 40%, 13%, 11%, and 8% for the DAS28-CRP, DAS28-ESR, Boolean, SDAI, and CDAI remission criteria, respectively. Remission rates using the DAS28 definition varied most among the b/tsDMARD subgroups.Conclusion:Assessment of sustained remission using the CDAI, SDAI, or Boolean criteria is more stringent, yet congruous with the DAS28-based criteria in RA patients treated with b/tsDMARDs.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-13T08:50:59Z
      DOI: 10.1177/1759720X221096363
      Issue No: Vol. 14 (2022)
       
  • Evaluation of local tissue peri-implant reaction in total knee
           arthroplasty failure cases

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      Authors: Ava Brozovich, Terry Clyburn, Kevin Park, Katharine D. Harper, Thomas Sullivan, Stephen Incavo, Francesca Taraballi
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:Implant-related hypersensitivity is emerging as a causative factor as a potential source of total knee arthroplasty (TKA) failure. Mechanistically, this type IV hypersensitivity reaction (T4HR) is mediated by effector T-cells, macrophages, and leukocytes that infiltrate to the site of implant and react to metal exposure and induce inflammatory tissue damage.Methods:A case–control study was performed where cortical bone was taken at the time of revision surgery for all patients operated on for primary TKA in which metal allergy was suspected and for revision TKA cases done for presumed metal allergy. Cytof was used to determine the cell density of inflammatory cells, specifically Th1, Th2, M1, and M2 cells.Results:Comparing the mean cell density of primary versus revision TKA, revision TKA patients had significantly higher number of Th2 cells compared with Th1 cells (p = 0.0043). Among revision cases, there were significantly more M1 versus M2 macrophages (p = 0.034) within a patient. When comparing mean cell density of M1 versus M2 macrophages, there was a significant difference in both primary and revision TKA surgeries (p = 0.0041 primary, p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-05-02T01:34:57Z
      DOI: 10.1177/1759720X221092263
      Issue No: Vol. 14 (2022)
       
  • Clinical and immunological study of Tofacitinib and Baricitinib in
           refractory Blau syndrome: case report and literature review

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      Authors: Carmen Álvarez-Reguera, Diana Prieto-Peña, Alba Herrero-Morant, Lara Sánchez-Bilbao, José Luis Martín-Varillas, Elena González-López, María Gutiérrez-Larrañaga, David San Segundo, Rosalía Demetrio-Pablo, Gonzalo Ocejo-Vinyals, Miguel A. González-Gay, Ricardo Blanco
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Blau syndrome (BS) is an autoinflammatory disorder characterized by non-caseating granulomatous dermatitis, arthritis, and uveitis. We present a case of refractory and severe BS that was treated with the Janus kinase inhibitors (JAKINIBS), Tofacitinib (TOFA) and then Baricitinib (BARI). Our aim was to describe the clinical and immunological outcomes after treatment with JAKINIBS. Blood tests and serum samples were obtained during follow-up with TOFA and BARI. We assessed their effects on clinical outcomes, acute phase reactants, absolute lymphocyte counts (ALCs), lymphocyte subset counts, immunoglobulins, and cytokine levels. A review of the literature on the use of JAKINIBS for the treatment of uveitis and sarcoidosis was also conducted. TOFA led to a rapid and maintained disease control and a steroid-sparing effect. A decrease from baseline was observed in ALC, CD3+, CD4+, CD8+, and natural killer (NK) cell counts. B-cells were stable. Serum levels of interleukin (IL)-4 and tumor necrosis factor alpha (TNF-α) increased, whereas IL-2, IL-6, IL-10, and IL-17 maintained stable. TOFA was discontinued after 19 months due to significant lymphopenia. The initiation of BARI allowed maintaining adequate control of disease activity with an adequate safety profile. The literature review showed seven patients with uveitis and five with sarcoidosis treated with JAKINIBS. No cases of BS treated with JAKINIBS were found. We report the successful use of JAKINIBS in a patient with refractory and severe BS.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-29T07:24:30Z
      DOI: 10.1177/1759720X221093211
      Issue No: Vol. 14 (2022)
       
  • Risk factors associated with the occurrence of total knee arthroplasty in
           patients with knee osteoarthritis: a nested case–control study

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      Authors: Jean-Pierre Pelletier, Marc Dorais, Patrice Paiement, Jean-Pierre Raynauld, Johanne Martel-Pelletier
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:The aim of this study was to investigate changes over time in osteoarthritis risk factors most closely associated with the occurrence of total knee arthroplasty (TKA). We hypothesize that the robustness of a longitudinal case–control study will provide new information on the association between changes in various clinical and structural parameters in different time frames before TKA.Methods:Cases (195; TKA after cohort entry) and controls (468) matched for age, gender, income, WOMAC pain, Kellgren–Lawrence grade and follow-up duration were from the Osteoarthritis Initiative cohort. Associations between changes in sociodemographic, clinical, imaging and osteoarthritis therapies with the occurrence of TKA were performed using conditional logistic regression analyses.Results:Worsening of WOMAC scores (cOR 1.02–1.20, p ⩽ 0.012), KOOS (1.02–1.04, p ⩽ 0.014), knee injuries sustained in the previous 30–40 years (women 2.70, p = 0.034) and valgus alignment (1.10, p = 0.052) were associated with the occurrence of TKA. Also associated with TKA was cartilage volume loss in the lateral (overall 1.76, p = 0.025; women 1.93, p = 0.047) and medial compartments (⩾10%, overall 1.54, p = 0.027; men 2.34, p = 0.008), occurrence of medial meniscal extrusion (overall 1.77, p = 0.046; men 2.86, p = 0.028), and increase in bone marrow lesions (BMLs) for women (1.09, p = 0.048). The association of risk factors with TKA was reinforced when both an increase in WOMAC pain and cartilage volume loss (1.85, p = 0.001) were combined. Pain medication usage, mainly narcotics and intra-articular steroid injections (IASI), was also associated with TKA, with no impact on changes in cartilage loss or structure.Conclusion:This study provides new information about gender differences in risk factors associated with the occurrence of TKA. Worsening of valgus alignment, cartilage volume loss in the lateral compartment, BMLs and older injuries are important risk factors in women, while medial compartment cartilage loss and meniscal extrusion are in men. The use of pain medication and IASI although associated was found not causal with TKA.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-29T07:22:19Z
      DOI: 10.1177/1759720X221091359
      Issue No: Vol. 14 (2022)
       
  • Effectiveness and safety of secukinumab in axial spondyloarthritis: a
           24-month prospective, multicenter real-life study

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      Authors: Roberta Ramonda, Mariagrazia Lorenzin, Maria Sole Chimenti, Salvatore D’Angelo, Antonio Marchesoni, Carlo Salvarani, Ennio Lubrano, Luisa Costa, Ylenia Dal Bosco, Elena Fracassi, Augusta Ortolan, Mario Ferraioli, Antonio Carriero, Elisa Visalli, Riccardo Bixio, Francesca Desiati, Alberto Bergamini, Elisa Pedrollo, Andrea Doria, Rosario Foti, Antonio Carletto
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:To evaluate, in a multicentric Italian cohort of axial spondyloarthritis (axSpA) patients on Secukinumab (SEC) followed for 24 months: (1) the long-term effectiveness and safety of SEC; (2) the drug retention rate and low disease activity (LDA) measured as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-29T07:19:02Z
      DOI: 10.1177/1759720X221090310
      Issue No: Vol. 14 (2022)
       
  • Mortality related to COVID-19 in patients with rheumatic and
           musculoskeletal diseases, first wave of the outbreak: a single-center
           study

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      Authors: Dalifer Freites Nuñez, Leticia Leon, Alfredo Madrid Garcia, Jose Ignacio Colomer Arce, Arkaitz Mucientes, Benjamin Gutierrez-Fernandez, Luis Rodriguez, Inés Pérez San Cristóbal, Paula Álvarez, Cristina Martinez Prada, Lydia Abasolo
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:The aim of this study was to assess the cause-specific mortality rate related to COVID-19 (CMR) in patients with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 and to analyze the role of the different RMDs in their mortality risk.Methods:An observational longitudinal study was conducted during the first pandemic wave in our center. Patients with the diagnosis of RMDs and COVID-19 were included. Main outcome is the death related to COVID-19. Independent variable – type of RMDs: autoimmune rheumatic diseases (ARD), such as chronic inflammatory arthritis (CIA) and connective tissue diseases (CTD) and non-autoimmune Rheumatic Diseases (non-ARD). Survival techniques were used to estimate the CMR per 1000 patients-month with a 95% confidence interval (CI), and Cox multivariate regression analysis was run to examine the effect of ARD compared to non-ARD on mortality risk adjusted by confounders. Results were expressed by Hazard Ratio (HR) and CI.Results:Overall, 405 patients were included (642.5 patients-month). During the study period, 44 (10.86%) deaths were recorded. CMR was 68.48 (50.96–92.01). After adjusting for confounders, HR of mortality in ARD compared to non-ARD did not achieve statistical significance [HR: 1.15 (0.64–2.07)], neither CTD versus CIA nor CTD versus non-ARD. Age and certain comorbidities which are being diagnosed in March compared to April or May [HR: 2.43 (1.1–5.55)] increased the mortality risk. Glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) dropped from the final model.Conclusion:In patients with RMDs and COVID-19, CMR was 6.8% patients-month. This study shows that mortality risk is higher in males, older patients, and similar between CTD, CIA, and non-ARD. COVID-19 management improved after the first month of pandemic.Plain Language SummariesMortality related to the outbreak of COVID-19 in patients with rheumatic and musculoskeletal diseasesWhy was this study done'- To report the COVID-19-specific mortality rate in patients with a variety of RMDs during the first pandemic peak in a tertiary hospital in Madrid and to analyze the role of specific types of ARD and other possible factors in the risk of death related to COVID-19.What did the researchers do'- We performed a retrospective observational study during the first wave of the COVID-19 pandemic in Madrid, Spain.What did the researchers find'- In this study, neither the different diagnoses of RMDs, including CIA, CTD, or non-ARD disease or its treatment were not implicated as a potential risk of death related to COVID-19- In consonance with other studies, RMDs patients and COVID-19, older age, male sex, and certain comorbidities implied more mortality risk- Our data reflect COVID-19 severity in a particular context, time, and population. In times of the absence of COVID-19 vaccine, healthcare, social, and political measures taken to contain the coronavirus outbreak have worked properly.What do the findings mean'- The presence of comorbidities in RMDs patients represents a greater risk than the different types of RMDs themselves, in the development of COVID-19 fatal outcome. It is important to integrate the control of comorbidities in the daily management.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-29T07:13:16Z
      DOI: 10.1177/1759720X221090296
      Issue No: Vol. 14 (2022)
       
  • Is there still a place for methotrexate in severe psoriatic arthritis'

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      Authors: Renaud Felten, Grégoire Lambert De Cursay, Eric Lespessailles
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      The management of psoriatic arthritis (PsA) has long been equated with that of rheumatoid arthritis (RA), particularly because methotrexate (MTX) was found efficient in RA in the 1990s. However, results of collective evidence-based medicine, included and argued in this narrative review, do not currently support the use of MTX as first-line therapy in severe PsA. A recent Cochrane systematic review examining the efficacy of MTX in PsA concluded that low-dose MTX was only slightly more effective than placebo. Questions about a structural effect of MTX in PsA remains non-elucidated. Even if tolerance data on MTX are more consensual and adverse events generally non-severe, subjective side effects such as fatigue might lead to MTX withdrawal based on the patient’s decision. PsA patients with axial disease, radiographic lesions, and extensive and disabling skin or joint involvement should receive early treatment with targeted therapy and no longer with MTX. Finally, the usefulness of MTX combined with targeted therapies is limited. MTX does not affect efficacy but only seems to increase the therapeutic maintenance of monoclonal TNF inhibitors. This narrative review may help clarify the place of MTX in PsA management. It allows for reflection on the evolution of current concepts and practices.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-19T12:00:25Z
      DOI: 10.1177/1759720X221092376
      Issue No: Vol. 14 (2022)
       
  • SCORE2 versus SCORE in patients with systemic lupus erythematosus

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      Authors: Juan Carlos Quevedo-Abeledo, Miguel Á. González-Gay, Iván Ferraz-Amaro
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:Systemic lupus erythematosus (SLE) has been associated with an increased risk of cardiovascular (CV) disease. Recently, the Systematic Coronary Risk Assessment (SCORE), a well-known CV risk algorithm, has been updated to a new predictive model (SCORE2). This new algorithm improves the identification of individuals at high risk of developing CV disease across Europe. Since carotid atherosclerosis is a predictor of future CV events and CV death, our objective was to compare the predictive capacity of SCORE2 versus SCORE for the presence of subclinical carotid atherosclerosis in patients with SLE.Methods:Two hundred and thirty-five individuals over 40 years of age diagnosed with SLE were consecutively recruited in this cross-sectional study. SCORE and SCORE2 were calculated. The relationship of SCORE and SCORE2 with each other, and with the presence of subclinical carotid atherosclerosis (both carotid plaque and carotid intima media thickness -cIMT-), was studied.Results:SCORE2 and SCORE did not correlate with each other (Spearman’s Rho = 0.125, p = 0.065). Although SCORE did not correlate with cIMT (Spearman’s Rho = -0.022, p = 0.75), the correlation of SCORE2 with cIMT was statistically significant (Spearman’s Rho = 0.367, p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-19T11:58:24Z
      DOI: 10.1177/1759720X221092373
      Issue No: Vol. 14 (2022)
       
  • Comparison of the efficacy and risk of discontinuation between
           non-TNF-targeted treatment and a second TNF inhibitor in patients with
           rheumatoid arthritis after first TNF inhibitor failure

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      Authors: Dong-Jin Park, Sung-Eun Choi, Ji-Hyoun Kang, Kichul Shin, Yoon-Kyoung Sung, Shin-Seok Lee
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:Despite improved care for rheumatoid arthritis (RA) patients, many still experience treatment failure with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs [tsDMARDs; typically Janus kinase inhibitors (JAKi)], and eventually switch to other agents. We compared the efficacy of a second tumor necrosis factor inhibitor (TNFi) and non-TNF-targeted treatment as the second-line treatment in patients showing an insufficient response to the first TNFi.Methods:Patients were included if they had received at least one prescription for a TNFi, and at least one follow-up prescription for a second TNFi or non-TNF-targeted treatment after discontinuation of the first drug. In total, 209 patients were analyzed, including 69 with a second TNFi and 140 with a non-TNF-targeted treatment (106 non-TNFi biologics and 34 JAKi). Cox regression was used to estimate the hazard ratio (HR) for discontinuation.Results:The mean follow-up period after switching was 28.0 (range: 0–80) months and 24.4% of the 209 patients switched or discontinued the second drug. In multivariate Cox proportional hazard analysis, the non-TNF-targeted treatment group had a lower likelihood of discontinuing their treatment than the second TNFi group [HR = 0.326, 95% confidence interval (CI): 0.170–0.626, p = 0.001]. When analyzed separately, the risk of discontinuation was significantly lower in both the non-TNFi biologic (HR = 0.318, 95% CI: 0.160–0.633, p = 0.001) and JAKi (HR = 0.356, 95% CI: 0.129–0.980, p = 0.046) groups than in the second TNFi group.Conclusion:Our study supported switching to a non-TNF-targeted treatment instead of TNF cycling in patients with RA showing an inadequate response to initial TNFi.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-19T11:55:23Z
      DOI: 10.1177/1759720X221091450
      Issue No: Vol. 14 (2022)
       
  • Immunogenicity and safety of inactivated and mRNA COVID-19 vaccines in
           patients with systemic lupus erythematosus

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      Authors: Ho So, Tena Li, Vivien Chan, Lai-Shan Tam, Paul KS Chan
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objective:To evaluate the effects and side effects of both inactivated and mRNA COVID-19 vaccines in patients with systemic lupus erythematosus (SLE).Methods:This was a prospective, single-center, observational study. Patients with SLE planning to receive COVID-19 vaccines were recruited and matched 1:1 with healthy controls. The immunogenicity of the COVID-19 vaccines was assessed by a surrogate neutralization assay at 28 days after the second dose. The main outcome was the antibody response comparing SLE patients and controls. Other outcomes included reactogenicity, disease activity and predictors of antibody responses in patients with SLE.Results:Sixty-five SLE patients received 2 doses of COVID-19 vaccines (Comirnaty: 38; CoronaVac: 27) were recruited. Many of them were on systemic glucocorticoids (76%) and immunosuppressants (55%). At day 28 after the second dose of vaccines, 92% (Comirnaty: 100% vs CoronaVac: 82%, p = 0.01) of the patients had positive neutralizing antibody. However, compared to the age, gender, vaccine type matched controls, the level of neutralizing antibody was significantly lower (p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-19T11:53:26Z
      DOI: 10.1177/1759720X221089586
      Issue No: Vol. 14 (2022)
       
  • Pharmacovigilance pregnancy data in a large population of patients with
           chronic inflammatory disease exposed to certolizumab pegol

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      Authors: Megan Clowse, Rebecca Fischer-Betz, Catherine Nelson-Piercy, Angela E. Scheuerle, Brigitte Stephan, Marla Dubinsky, Thomas Kumke, Rachna Kasliwal, Bernard Lauwerys, Frauke Förger
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:Chronic inflammatory diseases (CIDs), including rheumatic diseases and other inflammatory conditions, often affect women of reproductive age. Tumor necrosis factor inhibitors (TNFi) are widely used to treat CID, but there is limited information on outcomes of TNFi-exposed pregnancies. We evaluated pregnancy outcomes from 1392 prospectively reported pregnancies exposed to certolizumab pegol (CZP), a PEGylated, Fc-free TNFi with no to minimal placental transfer.Methods:CZP-exposed pregnancies in patients with CID from the UCB Pharmacovigilance global safety database were reviewed from the start of CZP clinical development (July 2001) to 1 November 2020. To limit bias, the analysis focused on prospectively reported cases with known pregnancy outcomes.Results:In total, 1392 prospective pregnancies with maternal CZP exposure and known pregnancy outcomes (n = 1425) were reported; 1021 had at least first-trimester CZP exposure. Live birth was reported in 1259/1425 (88.4%) of all prospective outcomes. There were 150/1425 (10.5%) pregnancy losses before 20 weeks (miscarriage/induced abortion), 11/1425 (0.8%) stillbirths, and 5/1392 (0.4%) ectopic pregnancies. Congenital malformations were present in 30/1259 (2.4%) live-born infants, of which 26 (2.1%) were considered major according to the Metropolitan Atlanta Congenital Defects Program criteria. There was no pattern of congenital malformations.Discussion and conclusion:No signal for adverse pregnancy outcomes or congenital malformations was observed in CZP-exposed pregnancies. Although the limitations of data collected through this methodology (including underreporting, missing information, and absence of a comparator group) should be considered, these data provide reassurance for women with CID who require CZP treatment during pregnancy, and their treating physicians.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-04-15T10:41:19Z
      DOI: 10.1177/1759720X221087650
      Issue No: Vol. 14 (2022)
       
  • Increased risks of aortic regurgitation and atrial fibrillation in
           radiographic axial spondyloarthritis patients: a 10-year nationwide cohort
           study

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      Authors: Hong Ki Min, Hae-Rim Kim, Sang-Heon Lee, Sojeong Park, Minae Park, Yeon Sik Hong, Moon-Young Kim, Sung-Hwan Park, Kwi Young Kang
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:To compare the incidences of aortic regurgitation, atrial fibrillation (AF), and atrioventricular (AV) block II–III between radiographic axial spondyloarthritis (r-axSpA) patients and the general population (GP).Methods:National Health Insurance Services data were used. R-axSpA patients (N = 8877) and the age- and sex-matched GP (N = 26,631) were followed from August 2006 to December 2019. Incidence rates and standardized incidence ratios (SIRs) of aortic regurgitation, AF, and AV block II–III were compared between these groups. Ten-year incidence rates and hazard ratios (HRs) were calculated by the Kaplan–Meier method and Cox regression analysis.Results:Incidence rates of aortic regurgitation, AV block II–III, and AF in the r-axSpA group were 0.42, 0.21, and 4.0 per 1000 person-years (PYs), respectively. In the r-axSpA group, the SIR for aortic regurgitation was highest among 40- to 49-year-old men (4.11). Incidence rates of aortic regurgitation and AF were higher in the r-axSpA group than in the GP group (0.42 versus 0.18 per 1000 PYs 4.00 versus 3.13 per 1000 PYs, both p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-30T10:04:36Z
      DOI: 10.1177/1759720X221088094
      Issue No: Vol. 14 (2022)
       
  • A glimpse into the future of systemic lupus erythematosus

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      Authors: Martin Aringer, Marta E. Alarcón-Riquelme, Megan Clowse, Guillermo J. Pons-Estel, Edward M. Vital, Maria Dall’Era
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      This viewpoint article on a forecast of clinically meaningful changes in the management of systemic lupus erythematosus (SLE) in the next 10 years is based on a review of the current state of the art. The groundwork has been laid by a robust series of classification criteria and treatment recommendations that have all been published since 2019. Building on this strong foundation, SLE management predictably will take significant steps forward. Assessment for lupus arthritis will presumably include musculoskeletal sonography. Large-scale polyomics studies are likely to unravel more of the central immune mechanisms of the disease. Biomarkers predictive of therapeutic success may enter the field; the type I interferon signature, as a companion for use of anifrolumab, an antibody against the common type I interferon receptor, is one serious candidate. Besides anifrolumab for nonrenal SLE and the new calcineurin inhibitor voclosporin in lupus nephritis, both of which are already approved in the United States and likely to become available in the European Union in 2022, several other approaches are in advanced clinical trials. These include advanced B cell depletion, inhibition of costimulation via CD40 and CD40 ligand (CD40L), and Janus kinase 1 (Jak1) and Tyrosine kinase 2 (Tyk2) inhibition. At the same time, essentially all of our conventional therapeutic armamentarium will continue to be used. The ability of patients to have successful SLE pregnancies, which has become much better in the last decades, should further improve, with approaches including tumor necrosis factor blockade and self-monitoring of fetal heart rates. While we hope that the COVID-19 pandemic will soon be controlled, it has highlighted the risk of severe viral infections in SLE, with increased risk tied to certain therapies. Although there are some data that a cure might be achievable, this likely will remain a challenge beyond 10 years from now.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-30T10:02:36Z
      DOI: 10.1177/1759720X221086719
      Issue No: Vol. 14 (2022)
       
  • Validation of the ASDAS with a quick quantitative CRP assay (ASDAS-Q) in
           patients with axial SpA: a prospective multicentre cross-sectional study

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      Authors: Fabian Proft, Julia Schally, Henning Christian Brandt, Jan Brandt-Juergens, Gerd Rüdiger Burmester, Hildrun Haibel, Henriette Käding, Kirsten Karberg, Susanne Lüders, Burkhard Muche, Mikhail Protopopov, Judith Rademacher, Valeria Rios Rodriguez, Murat Torgutalp, Maryna Verba, Silke Zinke, Denis Poddubnyy
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:The objective of the study was to validate the Ankylosing Spondylitis Disease Activity Score (ASDAS) based on a quick quantitative C-reactive protein (qCRP) assay (ASDAS-Q) in a multicentre, prospective, cross-sectional study in patients with axial spondyloarthritis (axial SpA).Methods:Disease activity assessment was performed in prospectively recruited patients with axial SpA. Routine laboratory CRP was determined in the central laboratory of each study centre, while quick qCRP and erythrocyte sedimentation rate (ESR) were measured locally. Consequently, ASDAS-CRP, ASDAS-Q using the qCRP and ASDAS-ESR were calculated. The absolute agreement on the disease activity category ascertainment was analysed with cross-tabulations and weighted Cohen’s kappa. Bland–Altman plots and intraclass correlation coefficients (ICCs) were used to analyse the criterion validity.Results:Overall, 251 axial SpA patients were included in the analysis. The mean qCRP value (6.34 ± 11.13 mg/l) was higher than that of routine laboratory CRP (5.26 ± 9.35 mg/l). The ICC for routine laboratory CRP versus qCRP was 0.985 [95% confidence interval (CI): 0.972–0.991]. Comparing ASDAS-Q with ASDAS-CRP, 242 of 251 (96.4%) patients were assigned to the same disease activity categories with a weighted Cohen’s kappa of 0.966 (95% CI: 0.943–0.988) and ICC of 0.997 (95% CI: 0.994–0.999).Conclusions:ASDAS-Q showed an almost perfect agreement with ASDAS-CRP in the assignment to specific disease activity categories. Consequently, ASDAS-Q using the qCRP value can be applied as an accurate and quickly available alternative to ASDAS-CRP, thus facilitating the implementation of the treat-to-target concept in clinical trials and clinical routine.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-30T10:00:38Z
      DOI: 10.1177/1759720X221085951
      Issue No: Vol. 14 (2022)
       
  • Psoriatic arthritis: prospects for the future

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      Authors: Simon Hackett, Alexis Ogdie, Laura C. Coates
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Psoriatic arthritis (PsA) is a form of chronic inflammatory arthritis associated with psoriasis and a multitude of other symptoms, most commonly arthritis, dactylitis, enthesitis and axial involvement. PsA is significantly heterogeneous, with a highly variable clinical course of PsA. Patients may experience significant or mild skin and joint symptoms, with some patients developing rapidly progressing joint destruction and skin symptoms. Despite the range of symptom severity, PsA is frequently associated with significantly impaired quality of life from joint destruction, as well as chronic pain and a range of comorbidities such as depression and cardiovascular disease. Currently, there are no definitive diagnostic tests for PsA, with diagnosis remaining challenging owing to the heterogeneous presentation and course of the disease. Presently, the CASPAR criteria are often used to aid rheumatologists in distinguishing PsA from other inflammatory arthritides. Treatment options for patients have been expanded over the last two decades with the emerging clinical utility of biological therapies. However, early identification and diagnosis of patients and effective disease control remain unmet medical needs within the PsA community. In addition, predicting response to treatment also remains a challenge to rheumatologists. This review highlights the current hurdles faced by healthcare professionals in the diagnosis and management of PsA patients and provides future action points for consideration by the members of the multidisciplinary team who treat PsA patients.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-28T12:41:39Z
      DOI: 10.1177/1759720X221086710
      Issue No: Vol. 14 (2022)
       
  • Autologous hematopoietic stem cell transplantation modifies specific
           aspects of systemic sclerosis-related microvasculopathy

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      Authors: Maynara Santana-Gonçalves, Djúlio Zanin-Silva, Álvaro Henrique-Neto, Daniela A. Moraes, Marianna Y. Kawashima- Vasconcelos, João R. Lima-Júnior, Juliana B. E. Dias, Vinícius Bragagnollo, Júlia T. C. de Azevedo, Dimas T. Covas, Kelen C. R. Malmegrim, Leandra Ramalho, Maria Carolina Oliveira
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objective:Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic option for patients with severe and progressive systemic sclerosis (SSc). Here, we aimed to investigate how AHSCT affects the vasculopathy of SSc patients.Methods:Twenty-seven SSc patients were retrospectively assessed, before and after AHSCT, for vessel morphology (nailfold capillaroscopy), skin expression of endothelial markers and serum levels of markers of inflammation, angiogenesis and endothelial activation. Skin biopsies were analyzed by immunohistochemistry (IHC) for expression of CD31, VE-cadherin, E-selectin, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), Tie-2, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and endothelin-1 before and 12 months post-AHSCT. Serum samples from SSc patients were assessed before and up to 36 months after AHSCT for IL-6, von Willebrand factor (vWF), CXC Motif Chemokine Ligand 8 (CXCL8), Endothelin-1, epidermal growth factor (EGF), VEGFA, Pentraxin-3, Intercellular Adhesion Molecule 1 (ICAM-1), E-selectin, P-selectin, Thrombomodulin and IL-18 levels, and compared to healthy control samples.Results:On nailfold capillaroscopy, the number of capillaries increased at 1 year, while giant capillaries decreased at 6 months and 1 year after AHSCT. In the skin biopsies, expression of E-selectin notably decreased and Ang1 increased after AHSCT. At baseline, all vascular markers evaluated in the serum were significantly higher in SSc patients when compared to healthy controls, except for ICAM-1. When compared at different time points after AHSCT, Thrombomodulin, Pentraxin-3, vWF, and IL-18 levels remained generally stable at high levels until 36 months after AHSCT.Conclusion:Our results suggest that AHSCT contributes to improvements of the vessel morphology and dermal microvasculopathy, but does not normalize elevated levels of serum vascular markers in SSc patients. Additional vascular therapeutic approaches might contribute to more effectively treat the endothelial injury.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-28T12:39:10Z
      DOI: 10.1177/1759720X221084845
      Issue No: Vol. 14 (2022)
       
  • Digital health interventions for osteoporosis and post-fragility fracture
           care

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      Authors: Amit Gupta, Christina Maslen, Madhavi Vindlacheruvu, Richard L. Abel, Pinaki Bhattacharya, Paul A. Bromiley, Emma M. Clark, Juliet E. Compston, Nicola Crabtree, Jennifer S. Gregory, Eleni P. Kariki, Nicholas C. Harvey, Eugene McCloskey, Kate A. Ward, Kenneth E.S. Poole
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      The growing burden from osteoporosis and fragility fractures highlights a need to improve osteoporosis management across healthcare systems. Sub-optimal management of osteoporosis is an area suitable for digital health interventions. While fracture liaison services (FLSs) are proven to greatly improve care for people with osteoporosis, such services might benefit from technologies that enhance automation. The term ‘Digital Health’ covers a variety of different tools including clinical decision support systems, electronic medical record tools, patient decision aids, patient apps, education tools, and novel artificial intelligence (AI) algorithms. Within the scope of this review are AI solutions that use algorithms within health system registries to target interventions. Clinician-targeted, patient-targeted, or system-targeted digital health interventions could be used to improve management and prevent fragility fractures. This review was commissioned by The Royal Osteoporosis Society and Bone Research Academy during the production of the 2020 Research Roadmap (https://theros.org.uk), with the intention of identifying gaps where targeted research funding could lead to improved patient health. We explore potential uses of digital technology in the general management of osteoporosis. Evidence suggests that digital technologies can support multidisciplinary teams to provide the best possible patient care based on current evidence and to support patients in self-management. However, robust randomised controlled studies are still needed to assess the effectiveness and cost-effectiveness of these technologies.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-28T12:37:41Z
      DOI: 10.1177/1759720X221083523
      Issue No: Vol. 14 (2022)
       
  • Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2
           studies

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      Authors: Ravi Savarirayan, Josep Maria De Bergua, Paul Arundel, Helen McDevitt, Valerie Cormier-Daire, Vrinda Saraff, Mars Skae, Borja Delgado, Antonio Leiva-Gea, Fernando Santos-Simarro, Jean Pierre Salles, Marc Nicolino, Massimiliano Rossi, Peter Kannu, Michael B. Bober, John Phillips, Howard Saal, Paul Harmatz, Christine Burren, Garrett Gotway, Terry Cho, Elena Muslimova, Richard Weng, Daniela Rogoff, Julie Hoover-Fong, Melita Irving
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Achondroplasia is the most common short-limbed skeletal dysplasia resulting from gain-of-function pathogenic variants in fibroblast growth factor receptor 3 (FGFR3) gene, a negative regulator of endochondral bone formation. Most treatment options are symptomatic, targeting medical complications. Infigratinib is an orally bioavailable, FGFR1–3 selective tyrosine kinase inhibitor being investigated as a direct therapeutic strategy to counteract FGFR3 overactivity in achondroplasia.Objectives:The main objective of PROPEL is to collect baseline data of children with achondroplasia being considered for future enrollment in interventional studies sponsored by QED Therapeutics. The objectives of PROPEL 2 are to obtain preliminary evidence of safety and efficacy of oral infigratinib in children with achondroplasia, to identify the infigratinib dose to be explored in future studies, and to characterize the pharmacokinetic (PK) profile of infigratinib and major metabolites.Design:PROPEL (NCT04035811) is a prospective, noninterventional clinical study designed to characterize the natural history and collect baseline data of children with achondroplasia over 6−24 months. PROPEL 2 (NCT04265651), a prospective, phase II, open-label study of infigratinib in children with achondroplasia, consists of a dose-escalation, dose-finding, and dose-expansion phase to confirm the selected dose, and a PK substudy.Methods and analysis:Children aged 3−11 years with achondroplasia who completed ⩾6 months in PROPEL are eligible for PROPEL 2. Primary endpoints include treatment-emergent adverse events and change from baseline in annualized height velocity. Four cohorts at ascending dose levels are planned for dose escalation. The selected dose will be confirmed in the dose-expansion phase.Ethics:PROPEL and PROPEL 2 are being conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, principles of the Declaration of Helsinki, and relevant human clinical research and data privacy regulations. Protocols have been approved by local health authorities, ethics committees, and institutions as applicable. Parents/legally authorized representatives are required to provide signed informed consent; signed informed assent by the child is also required, where applicable.Discussion:PROPEL and PROPEL 2 will provide preliminary evidence of the safety and efficacy of infigratinib as precision treatment of children with achondroplasia and will inform the design of future studies of FGFR-targeted agents in achondroplasia.Registration:ClinicalTrials.gov: NCT04035811; NCT04265651.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-21T11:59:52Z
      DOI: 10.1177/1759720X221084848
      Issue No: Vol. 14 (2022)
       
  • Osteoporosis in 10 years time: a glimpse into the future of osteoporosis

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      Authors: Giovanni Adami, Angelo Fassio, Davide Gatti, Ombretta Viapiana, Camilla Benini, Maria I. Danila, Kenneth G. Saag, Maurizio Rossini
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Patients living with osteoporosis are projected to increase dramatically in the next decade. Alongside the forecasted increased societal and economic burden, we will live a crisis of fractures. However, we will have novel pharmacological treatment to face this crisis and, more importantly, new optimized treatment strategies. Fracture liaison services will be probably implemented on a large scale worldwide, helping to prevent additional fractures in high-risk patients. In the next decade, novel advances in the diagnostic tools will be largely available. Moreover, new and more precise fracture risk assessment tools will change our ability to detect patients at high risk of fractures. Finally, big data and artificial intelligence will help us to move forward into the world of precision medicine. In the present review, we will discuss the future epidemiology and costs of osteoporosis, the advances in early and accurate diagnosis of osteoporosis, with a special focus on biomarkers and imaging tools. Then we will examine new and refined fracture risk assessment tools, the role of fracture liaison services, and a future perspective on osteoporosis treatment.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-21T04:43:01Z
      DOI: 10.1177/1759720X221083541
      Issue No: Vol. 14 (2022)
       
  • Circulating microRNAs differentiate fast-progressing from slow-progressing
           and non-progressing knee osteoarthritis in the Osteoarthritis Initiative
           cohort

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      Authors: Shabana Amanda Ali, Osvaldo Espin-Garcia, Andy K. Wong, Pratibha Potla, Chiara Pastrello, Madison McIntyre, Starlee Lively, Igor Jurisica, Rajiv Gandhi, Mohit Kapoor
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:The objective of this study is to identify circulating microRNAs that distinguish fast-progressing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative cohort by applying microRNA-sequencing.Methods:Participants with Kellgren–Lawrence (KL) grade 0/1 at baseline were included (N = 106). Fast-progressors were defined by an increase to KL 3/4 by 4-year follow-up (N = 20), whereas slow-progressors showed an increase to KL 2/3/4 only at 8-year follow-up (N = 35). Non-progressors remained at KL 0/1 by 8-year follow-up (N = 51). MicroRNA-sequencing was performed on plasma collected at baseline and 4-year follow-up from the same participants. Negative binomial models were fitted to identify differentially expressed (DE) microRNAs. Penalized logistic regression (PLR) analyses were performed to select combinations of DE microRNAs that distinguished fast-progressors. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate predictive ability.Results:DE analyses revealed 48 microRNAs at baseline and 2 microRNAs at 4-year follow-up [false discovery rate (FDR) 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-18T10:48:55Z
      DOI: 10.1177/1759720X221082917
      Issue No: Vol. 14 (2022)
       
  • Future challenges in rheumatology – is telemedicine the
           solution'

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      Authors: Annette de Thurah, Andrea Marques, Savia de Souza, Cynthia S. Crowson, Elena Myasoedova
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      The COVID-19 pandemic has become an unprecedented facilitator of rapid telehealth expansion within rheumatology. Due to demographic shifts and workforce shortages in the future, new models of rheumatology care will be expected to emerge, with a growing footprint of telehealth interventions. Telehealth is already being used to monitor patients with rheumatic diseases and initial studies show good results in terms of safety and disease progression. It is being used as a tool for appointment prioritization and triage, and there is good evidence for using telehealth in rehabilitation, patient education and self-management interventions. Electronic patient-reported outcomes (ePROs) offer a number of long-term benefits and opportunities, and a routine collection of ePROs also facilitates epidemiological research that can inform future healthcare delivery. Telehealth solutions should be developed in close collaboration with all stakeholders, and the option of a telehealth visit must not deprive patients of the possibility to make use of a conventional ‘face-to-face’ visit. Future studies should especially focus on optimal models for rheumatology healthcare delivery to patients living in remote areas who are unable to use or access computer technology, and other patient groups at risk for disparity due to technical inequity and lack of knowledge.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-17T12:41:34Z
      DOI: 10.1177/1759720X221081638
      Issue No: Vol. 14 (2022)
       
  • Delayed treatment with a tumor necrosis factor alpha blocker associated
           with worse outcomes in patients with spondyloarthritis: data from the
           Czech National Registry ATTRA

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      Authors: Tomas Milota, Jana Hurnakova, Karel Pavelka, Zlatuse Kristkova, Lucie Nekvindova, Rudolf Horvath
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:The administration of biologic disease-modifying antirheumatic drugs, including tumor necrosis factor (TNF)-α inhibitors, is observed to interfere with the disease activity and progression. In this study, we aimed to assess the effectiveness and response predictors of adalimumab (ADA), a TNF-α blocker, in patients with axial spondyloarthritis (AxSpA).Methods:This study was a historical prospective, registry-based observational study on patients with AxSpA treated with first-line ADA after conventional drug failure. For evaluation and comparison, patients were divided into three groups according to the number of years from AxSpA diagnosis to initiation of ADA treatment: (A) 10 years. The assessment instruments ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire (HAQ), Short Form 36 questionnaire (SF-36), and EuroQoL 5 dimension questionnaire (EQ-5D) were regularly administered for up to 24 months of follow-up.Results:This study included 1043 patients with AxSpA (9.2% with non-radiographic AxSpA, 68.9% men). By month 6, a significantly higher proportion of patients with ASDAS remission (
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-17T09:31:06Z
      DOI: 10.1177/1759720X221081649
      Issue No: Vol. 14 (2022)
       
  • Measuring sedentary behavior using waist- and thigh-worn accelerometers
           and inclinometers – are the results comparable'

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      Authors: Tobias Kalisch, Christoph Theil, Georg Gosheger, Thomas Ackmann, Isabell Schoenhals, Burkhard Moellenbeck
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Objective sensor-based quantification of sedentary behavior is an important tool for planning and evaluating interventions for excessive sedentary behavior in patients with musculoskeletal diseases. Although waist-worn accelerometers are the standard for physical activity (PA) assessment, only thigh-worn inclinometers can clearly distinguish sedentary behavior from any light PA or standing activity.Methods:In this study, 53 adults (ages 20–85 years) wore two ActiGraph wGT3X-BT monitors, each containing an inclinometer and accelerometer (set for acquisition of slow movements in all three planes), attached to the right waist and thigh for a period of about 4 days. Both monitors recorded total sedentary time and continuous sedentary 10-min bouts by synchronous accelerometry and inclinometry. Differences and correlations between methods and wearing positions were evaluated against participant age, body mass index (BMI), and number of steps taken. Thigh-worn inclinometry was used as reference.Results:Data from thigh-worn inclinometry and waist-worn accelerometry were highly correlated for total sedentary time [rho = 0.888; intraclass correlation coefficient (ICC) = 0.937] and time in sedentary bouts (rho = 0.818; ICC = 0.848). Nevertheless, accelerometry at the waist underestimated sedentary time by ≈17% (p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-15T11:40:14Z
      DOI: 10.1177/1759720X221079256
      Issue No: Vol. 14 (2022)
       
  • Efficacy and safety of biologic agents for the treatment of
           osteoarthritis: a meta-analysis of randomized placebo-controlled trials

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      Authors: Fanqiang Meng, Hui Li, Haoran Feng, Huizhong Long, Zidan Yang, Jiatian Li, Yuqing Wang, Dongxing Xie
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:We aimed to evaluate the efficacy and safety of biologic agents targeting three main cytokines, that is, nerve growth factor (NGF), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α), for osteoarthritis (OA) treatment.Methods:Databases (PubMed, Embase, and Cochrane Library) and ClinicalTrials.gov were systematically searched for randomized placebo-controlled trials (RCTs) of biologic agents from inception to November 15, 2020. The outcomes were the mean change in pain, function scores, and the risk of adverse effects (AEs).Results:Out of the 28 studies with 29 RCTs (8555 individuals) included, biologic agents were superior to placebo in pain relief (standardized mean difference [SMD] = 0.28, 95% confidence interval [CI] = 0.17–0.38, p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-08T11:59:08Z
      DOI: 10.1177/1759720X221080377
      Issue No: Vol. 14 (2022)
       
  • Pregnancy in juvenile idiopathic arthritis: maternal and foetal outcome,
           and impact on disease activity

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      Authors: Maria Gerosa, Cecilia Beatrice Chighizola, Francesca Pregnolato, Irene Pontikaki, Angela Flavia Luppino, Lorenza Maria Argolini, Laura Trespidi, Manuela Wally Ossola, Enrico M. Ferrazzi, Roberto Caporali, Rolando Cimaz
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objective:This retrospective cohort study describes the modulation of disease activity during gestation and in the year following delivery as well as maternal and neonatal outcomes in a monocentric cohort of women with juvenile idiopathic arthritis (JIA).Methods:Disease activity was assessed using DAS28-CRP before conception and every 3 months during pregnancy and in the first year postpartum. The risk of complicated pregnancies was measured applying a generalized estimating equation model. Changes in disease activity during gestation and in the first year postpartum were assessed in a linear mixed model for repeated measures.Results:Thirty-one women (49 pregnancies) with persisting JIA and at least one conception were enrolled. Adjusted DAS28-CRP levels remained stable from preconception through the first trimester, but increased significantly in the second and decreased not significantly in the third. In the postpartum, adjusted disease activity peaked at 3 months after delivery, stabilized at 6 months to decrease at 1 year, although not significantly. Preconceptional DAS28-CRP and number of biological drugs predicted disease activity fluctuation during gestation. The number of biological drugs and the length of gestational exposure to biologics significantly predicted pregnancy morbidity. In particular, JIA women had a higher probability of preterm delivery compared with healthy and disease controls. Adjusted for breastfeeding and DAS28-CRP score in the third trimester, postconceptional exposure to biologics was inversely related with disease activity in the postpartum: the longer the patient continued treatment, the lower the probability of experiencing an adverse pregnancy outcome.Conclusion:These data offer novel insights on how treatment affects disease activity during pregnancy and postpartum as well as obstetric outcomes in women with JIA.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-03-04T11:06:23Z
      DOI: 10.1177/1759720X221080375
      Issue No: Vol. 14 (2022)
       
  • Successful treatment of sirolimus in a Chinese patient with refractory LN
           and APS: a case report

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      Authors: Danting Zhang, Fangfang Sun, Shuang Ye
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      It has been reported that the mammalian target of rapamycin (mTOR) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE), and increasing evidence has shown the effect of mTOR-targeted therapies with sirolimus in SLE. The objective of this study was to report the successful treatment of sirolimus in a Chinese patient with refractory lupus nephritis (LN) and anti-phospholipid antibody syndrome (APS). A 44-year-old female with a previous diagnosis of autoimmune hemolytic anemia (AIHA) and APS secondary to SLE presented with lupus nephritis refractory to cyclophosphamide and mycophenolate. Renal biopsy met the criteria of WHO class III LN complicated by acute tubular injury and immunofluorescence confirmed the activation of the mTOR pathway. Treatment with the mTOR inhibitor sirolimus was initiated in this patient. Complete remission (CR) was achieved after 6 months, and flare-free remission was maintained for the next 3.5 years. The literature on the efficacy of sirolimus in patients with LN was reviewed. Although the available evidence is limited to retrospective studies with small sample sizes, sirolimus appeared to be efficacious in some patients with refractory LN. Well-designed clinical trials are warranted, and pathology-guided precision medicine might assist in guiding physicians’ treatment decisions.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-02-28T10:15:25Z
      DOI: 10.1177/1759720X221079253
      Issue No: Vol. 14 (2022)
       
  • The role of antifibrotics in the treatment of rheumatoid
           arthritis–associated interstitial lung disease

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      Authors: Minrui Liang, Eric L. Matteson, Andy Abril, Jörg H.W. Distler
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      The major pulmonary complication of rheumatoid arthritis (RA) is interstitial lung disease (ILD), which causes significant morbidity and mortality and influences the natural course of disease. Recent advances in the management of arthritis have improved patient outcomes. However, exceptionally high medical needs still remain for effective therapies for the patients with ILD in RA. Better understanding of the shared and distinct pathophysiology of fibrotic diseases led to the development of novel antifibrotic agents such as nintedanib and pirfenidone. The further stratification analysis of the phase III INBUILD trial demonstrated beneficial effects of nintedanib in RA-ILD with a progressive phenotype by reducing the rate of decline in forced vital capacity (FVC) over 52 weeks by 60%. Pirfenidone is another antifibrotic agent currently under phase II clinical study (TRAIL1) aiming to evaluate its effects for RA-ILD. This review provides an overview of state-of-the-art pathogenesis and the current therapeutic options for RA-ILD, with a focus on antifibrotic strategies.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-02-15T11:40:46Z
      DOI: 10.1177/1759720X221074457
      Issue No: Vol. 14 (2022)
       
  • Hydroxychloroquine in systemic lupus erythematosus: overview of current
           knowledge

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      Authors: Alina Dima, Ciprian Jurcut, François Chasset, Renaud Felten, Laurent Arnaud
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ’s effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-02-14T10:45:57Z
      DOI: 10.1177/1759720X211073001
      Issue No: Vol. 14 (2022)
       
  • Selection of X-ray versus magnetic resonance imaging as a first-line
           imaging modality for diagnosing axial spondyloarthritis

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      Authors: Oh Chan Kwon, Min-Chan Park
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:To determine the cut-off values for age and symptom duration that could be used in selecting preferential first-line imaging modality of sacroiliac joints [X-ray versus magnetic resonance imaging (MRI)] for diagnosing axial spondyloarthritis (axSpA).Methods:This retrospective cohort study included 388 patients newly diagnosed with axSpA. Patients were classified into radiographic axSpA (n = 322) and non-radiographic axSpA (n = 66) groups according to the fulfilment of modified New York criteria by X-ray. Patient characteristics of the two groups were compared. Receiver operating characteristic (ROC) curve analysis was conducted to determine the cut-off values for age and symptom duration that best distinguish non-radiographic axSpA from radiographic axSpA.Results:Compared with patients with radiographic axSpA, those with non-radiographic axSpA were younger at diagnosis (35.7 ± 11.3 years versus 26.8 ± 7.8 years, p  4.1 years (AUC: 0.787) were the cut-off values that best discriminate radiographic axSpA from non-radiographic axSpA.Conclusion:The best cut-off values for age and symptom duration for predicting radiographic sacroiliitis are 33.5 and 4.1 years, respectively. It is reasonable to use X-ray as a first-line imaging modality in patients older than 33.5 years with a symptom duration longer than 4.1 years, and use MRI as a first-line imaging in patients younger than 33.5 years with a symptom duration less than 4.1 years.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-02-14T10:41:59Z
      DOI: 10.1177/1759720X211072994
      Issue No: Vol. 14 (2022)
       
  • Erratum to “Clinical effectiveness of symptomatic therapy compared with
           standard step-up care for the treatment of low-impact psoriatic
           oligoarthritis: the two-arm parallel group randomised POISE feasibility
           study”

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      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.

      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-02-09T10:00:23Z
      DOI: 10.1177/1759720X221077827
      Issue No: Vol. 14 (2022)
       
  • A broad look into the future of rheumatoid arthritis

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      Authors: Johanna Mucke, Martin Krusche, Gerd R. Burmester
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Despite all improvements in rheumatoid arthritis, we are still not able to prevent or cure the disease. Diagnostic delays due to lack of access to a specialist and costly therapies are still a major obstacle for many patients. Even in first-world countries, the treat-to-target principle and the goal of disease remission are often missed. Thus, rheumatoid arthritis (RA) is still the reason for disability and reduced quality of life for many patients. So, is it time to move the goalpost even further' Where are we heading next' And will we finally be able to cure the disease' These questions are addressed in our review article.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-02-09T09:03:56Z
      DOI: 10.1177/1759720X221076211
      Issue No: Vol. 14 (2022)
       
  • Estimation of fracture risk by the FRAX tool in patients with systemic
           lupus erythematosus: a 10-year longitudinal validation study

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      Authors: Chi Chiu Mok, Sau Mei Tse, Kar Li Chan, Ling Yin Ho
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:The fracture risk assessment tool has been widely used to stratify the 10-year fracture risk to guide therapy. Using the actual fracture data of a 10-year longitudinal cohort of older patients with systemic lupus erythematosus, we reported an underestimation of the tool in predicting major symptomatic osteoporotic fractures. Treatment of osteoporosis in systemic lupus erythematosus should not be based on fracture risk estimation alone. Relevant time-dependent risk factors should be taken into account for an individualized decision.Objective:To compare the observed fracture incidence in a 10-year longitudinal cohort of patients with systemic lupus erythematosus (SLE) with the fracture risk prediction from the fracture risk assessment (FRAX) tool.Methods:Adult patients (⩾40 years) with SLE who had a first DEXA scan performed in 2005–2009 were studied. The 10-year rates of major osteoporotic and hip fractures were estimated by FRAX using clinical data at DEXA with adjustment for prednisolone dosage. The actual incidence of clinical fractures at 10 years was compared with the estimated rates. Factors associated with new fractures were studied by logistic regression.Results:A total of 229 SLE patients were studied (age: 50.2 ± 6.6 years, 93% women). Glucocorticoid was used in 148 (65%) patients at baseline (mean dose: 7.3 ± 6.9 mg/day; 34% ⩾ 7.5 mg/day). Osteoporosis (bone mineral density T score ⩽ –2.5) at the hip, femoral neck, or spine was present in 61 (27%) patients. The estimated 10-year risk of major osteoporotic and hip fractures by FRAX was 3.4 ± 4.5% and 0.95 ± 2.3%, respectively. After 10 years, three patients developed hip fracture, 6 patients had limb fractures and 20 patients had symptomatic vertebral fractures (major osteoporotic fracture 12.7%, hip fracture 1.3%). The actual major osteoporotic fracture rate was significantly higher than the FRAX estimation (12.7% vs 3.4%; p 
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-02-09T09:02:37Z
      DOI: 10.1177/1759720X221074451
      Issue No: Vol. 14 (2022)
       
  • Intra-articular placebo effect in the treatment of knee osteoarthritis: a
           survey of the current clinical evidence

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      Authors: Mir Sohail Fazeli, Louis McIntyre, Yili Huang, Xavier Chevalier
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Knee osteoarthritis (KOA) is a debilitating disease characterized by chronic pain, stiffness, and decreased mobility. Intra-articular injectable therapies show good clinical efficacy in improving symptoms; however, these therapies and their comparators (intra-articular saline) have been associated with a large underlying placebo effect. We aimed to describe the existing evidence on the challenges, hypotheses, and potential solutions to mitigate the intra-articular placebo effect in clinical trials in KOA. A targeted literature review was conducted by searching Embase, MEDLINE®, and CENTRAL using predefined study selection criteria. All eligible studies identified were extracted for relevant data, and results were narratively summarized. Forty-three studies were included following screening. Challenges associated with the intra-articular placebo effect included its ability to mask the comparative efficacy of active treatments in trials (n = 7 studies), long-lasting effects (up to 6 months; n = 3), and substantial variation of placebo effect sizes across populations (n = 3). Hypotheses for the mechanism of the placebo effect included aspiration of synovial fluid during administration (n = 6) and dilution of inflammatory mediators (n = 2). Factors affecting the placebo effect size were more invasive routes of administration (e.g., injection versus oral; n = 4) and patient expectations (n = 2). Proposed solutions included the suggestion for readers to weigh the relevance of clinical trial evidence against the presence of large underlying placebo effects (n = 9), discontinuation of intra-articular saline as an appropriate placebo (n = 5), and inclusion of ‘no treatment’ or sham injection as a control (n = 4). The intra-articular placebo effect is a well-documented occurrence in KOA clinical trials, and it is suggested that it be accounted for when designing randomized controlled trials. Awareness and understanding of the intra-articular placebo effect in KOA are required for fair interpretation of clinical trial evidence.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-01-31T12:46:15Z
      DOI: 10.1177/1759720X211066689
      Issue No: Vol. 14 (2022)
       
  • Safety and efficacy of SHR4640 combined with febuxostat for primary
           hyperuricemia: a multicenter, randomized, double-blind, phase II study

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      Authors: Honghu Tang, Beibei Cui, Yiyu Chen, Lin Chen, Zhihong Wang, Ning Zhang, Yanlan Yang, Xiaodong Wang, Xiangliang Xie, Lingyun Sun, Wantai Dang, Xianyang Wang, Runzi Li, Jianjun Zou, Yi Zhao, Yi Liu
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:To evaluate the safety, tolerability, and efficacy of SHR4640, a highly selective urate transporter-1 inhibitor, in combination with febuxostat, in patients with primary hyperuricemia.Methods:In this randomized, double-blind, parallel-controlled phase II study, patients whose fasting serum uric acid (sUA) levels were ⩾ 480 μmol/L at screening with gout or sUA levels were ⩾ 420 μmol/L lasting for at least 3 months without gout, either with sUA levels ⩾ 540 μmol/L at screening or sUA levels ⩾ 480 μmol/L with comorbidities at screening, were enrolled. Patients were randomized (1:1:1) to receive SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg orally once daily. The primary end point was the incidence of treatment-emergent adverse events (TEAEs).Results:A total of 93 patients were randomized and received treatment. TEAEs occurred in 55.9% of patients. The incidence of TEAEs was comparable among all the groups. Serious TEAEs occurred in one patient (1.1%), with no deaths observed. The proportion of patients who achieved the target sUA levels by week 4 was 79.3%, 96.6%, and 75.0% in the SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg groups, respectively. The mean percent reduction of sUA was 59.7%, 63.7%, and 41.8%, respectively.Conclusion:SHR4640 plus febuxostat exhibited a tolerable safety profile and substantial sUA lowering activity in patients with primary hyperuricemia.Registration:www.chinadrugtrials.org.cn; CTR 20192429
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-01-31T11:39:05Z
      DOI: 10.1177/1759720X211067304
      Issue No: Vol. 14 (2022)
       
  • The role of antifibrotic therapies in the treatment of systemic
           sclerosis–associated interstitial lung disease

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      Authors: Gonçalo Boleto, Jérôme Avouac, Yannick Allanore
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Systemic sclerosis (SSc) is a rare autoimmune condition with complex pathogenesis characterized by a heterogeneous presentation and different disease courses. Fibrosis of multiple organs including the lungs favored by inflammation and vasculopathy is the hallmark of SSc. SSc-associated interstitial lung disease (SSc-ILD) is common and can be associated with poor outcomes, this complication being the leading cause of death in recent series. Because of its huge heterogeneity, SSc-ILD management can be very challenging. Immunosuppressive therapy has long been used to prevent SSc-ILD progression with modest effects in clinical trials. However, thanks to a better understating of SSc pathogenesis, innovative therapies including antifibrotics are increasingly being developed. The achievement of the Safety and Efficacy of Nintedanib in Systemic SClerosIS (SENSCIS) trial has led to the approval by drug agencies of the first antifibrotic drug for SSc-ILD. In parallel, other antifibrotics are being investigated as possible beneficial therapies in SSc-ILD. An important unmet need remains to clarify the positioning of the various strategies, such as the added value of combination of immunosuppressants and antifibrotic therapies in patients at high risk of progression. Indeed, irreversible lung injury or self-perpetuated progression highlights the concept of a window of opportunity in SSc-ILD patients. Herewith, we provide an overview of the most significant clinical trials with antifibrotic drugs developed in recent years for the management of SSc-ILD and a viewpoint about their positioning in treatment algorithms.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-01-29T11:31:15Z
      DOI: 10.1177/1759720X211066686
      Issue No: Vol. 14 (2022)
       
  • An oleuropein-based dietary supplement may improve joint functional
           capacity in older people with high knee joint pain: findings from a
           multicentre-RCT and post hoc analysis

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      Authors: Marie-Noëlle Horcajada, Maurice Beaumont, Nicolas Sauvageot, Laure Poquet, Madleen Saboundjian, Berenice Costes, Peter Verdonk, Geoffrey Brands, Jean Brasseur, Didier Urbin-Choffray, Marc Vandenberghe, Karl Brabants, Kurt De Vlam, Werner Fache, Bernard Jandrain, Vincent Grek, Michel Malaise, Yves Henrotin
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Objectives:To investigate a 6-month intervention with an olive leaf extract (OLE) on knee functionality and biomarkers of bone/cartilage metabolism and inflammation.Design:This randomized, double-blind, placebo-controlled, multi-centric trial included 124 subjects with knee pain or mobility issues. Subjects received twice a day one capsule of placebo or 125 mg OLE (Bonolive™, an OLE containing 50 mg of oleuropein) for 6 months. The co-primary endpoints were Knee injury and Osteoarthritis Outcome Score (KOOS) and serum Coll2-1NO2. The secondary endpoints were the subscales of the KOOS, knee pain VAS at rest and at walking, OARSI core set of performance-based tests and multiple inflammatory and bone or cartilage remodeling serum biomarkers and concentration of oleuropein’s metabolites in urine.Results:At 6 months, OLE group was not efficient on global KOOS score, changes of inflammatory and cartilage remodeling biomarkers compared to placebo. Post hoc analyses demonstrated a large and significant treatment effect of OLE in a sub-group of subjects with high walking pain at baseline (p = 0.03). This was observed at 6 months for the global KOOS score, and each different subscale and for pain at walking (p = 0.02). OLE treatment was well tolerated.Conclusion:OLE was not effective on joint discomfort excepted in a sub-group of subjects with high pain at treatment initiation. As oleuropein is well tolerated, OLE can be used to relieve knee joint pain and enhance mobility in subjects with articular pain.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-01-20T04:55:10Z
      DOI: 10.1177/1759720X211070205
      Issue No: Vol. 14 (2022)
       
  • Poor health and functioning in patients with axial spondyloarthritis
           during the COVID-19 pandemic and lockdown: REUMAVID study (phase 1)

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      Authors: Diego Benavent, Marco Garrido-Cumbrera, Chamaida Plasencia-Rodríguez, Helena Marzo-Ortega, Laura Christen, José Correa-Fernández, Pedro Plazuelo-Ramos, Dale Webb, Victoria Navarro-Compán
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Aim:To evaluate the overall health and functioning in patients with axial spondyloarthritis (axSpA) and related factors affecting these during the COVID-19 pandemic and lockdown measures.Methods:Data from 587 axSpA patients participating in the first phase (April–July 2020) of the REUMAVID study who completed the ASAS Health Index (ASAS-HI) were analysed. REUMAVID is a cross-sectional study that collects data through an online survey to assess the impact of the COVID-19 pandemic on patients with rheumatic and musculoskeletal diseases across seven European countries. Poor health was defined as ASAS-HI ⩾ 12. The World Health Organization Five well-being index, self-perceived health status and change in health status during COVID-19 pandemic were evaluated as secondary outcomes. Logistic regression models were used to identify the factors associated with poor health.Results:According to the ASAS-HI, 147 (25.0%) patients reported poor health. Pain and moving around were the main affected categories. In addition, 14.0% reported their self-perceived health status as ‘bad’ or ‘very bad’ and 46.8% as worse than before the pandemic. In the multivariate analysis, smoking (OR = 1.98), diabetes (OR = 4.89) and taking painkillers (OR = 2.82) or corticosteroids use (OR = 2.20) were significantly associated with poor health, while engaging in physical activity (OR = 0.54) and being actively employed (OR = 0.48) were inversely associated with this.Conclusions:During the first wave of the COVID-19 pandemic, one in four axSpA patients reported poor health and functioning, while the self-perceived health status of almost half of these patients worsened. Nonsmoking, physical activity and being employed were associated with better outcomes.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-01-20T04:53:30Z
      DOI: 10.1177/1759720X211066685
      Issue No: Vol. 14 (2022)
       
  • Based on minimal clinically important difference values, a moderate dose
           of tanezumab may be a better option for treating hip or knee
           osteoarthritis: a meta-analysis of randomized controlled trials

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      Authors: Di Zhao, Ming-hui Luo, Jian-ke Pan, Ling-feng Zeng, Gui-hong Liang, Yan-hong Han, Jun Liu, Wei-yi Yang
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Background:Tanezumab is a nerve growth factor monoclonal antibody that may regulate pain in hip or knee osteoarthritis (OA). This meta-analysis was performed to evaluate the efficacy and safety of low and moderate doses of tanezumab in treating hip or knee OA.Methods:PubMed, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for clinical trials published before 1 May 2021. Patients were assessed via efficacy and safety outcomes.Results:Twelve randomized controlled trials including 6022 patients were identified. Both low and moderate doses of tanezumab significantly improved efficacy outcomes. However, only the point estimates (mean difference, MD) of moderate-dose tanezumab significantly exceeded the minimal clinically important differences (MCIDs). There were no significant differences in the incidence of treatment-related adverse events (AEs), withdrawals due to AEs, serious AEs, and total joint replacement between the tanezumab and placebo groups, whereas the incidence of AEs was higher in the tanezumab group (relative risk, RR = 1.10; 95% confidence interval, 95% CI = 1.04–1.17). The incidence of rapidly progressive OA was significantly higher in the combined low- and moderate-dose tanezumab groups than in the placebo group (RR = 5.01; 95% CI = 1.17–21.33). Furthermore, both low and moderate doses of tanezumab significantly increased the incidence of abnormal peripheral sensation (RR = 1.99, 95% CI = 1.21–3.28; RR = 2.64, 95% CI = 1.91–3.67, respectively). Compared with nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, tanezumab showed significantly improved efficacy outcomes (p  0.05).Conclusion:Tanezumab is efficacious in patients with hip or knee OA. Tanezumab is relatively well tolerated and safe but increases the incidence of AEs and reversible abnormal peripheral sensation. Additional studies on the occurrence of rapidly progressive OA are needed. A moderate dose of tanezumab may maximize the benefits for hip or knee OA.
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-01-19T06:50:24Z
      DOI: 10.1177/1759720X211067639
      Issue No: Vol. 14 (2022)
       
  • Wearable transcutaneous electrical nerve stimulation (actiTENS®) is
           effective and safe for the treatment of knee osteoarthritis pain: a
           randomized controlled trial versus weak opioids

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      Authors: Emmanuel Maheu, Sandrine Soriot-Thomas, Eric Noel, Hervé Ganry, Eric Lespessailles, Bernard Cortet
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:Despite their poor tolerance, especially in the elderly, weak opioids (WO) remain commonly prescribed for patients with knee osteoarthritis (KOA). We compared the efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) device with WO for the treatment of moderate-to-severe, nociceptive KOA chronic pain.Methods:The study was a non-inferiority, multicentric, prospective, randomized, single-blind, controlled, 2-parallel groups Trial. A total of 110 patients with KOA were included (Kellgren-Lawrence radiographic grade ⩾2; American College of Rheumatology criteria), with chronic moderate-to-severe nociceptive pain (mean 8-day pain intensity (PI) ⩾ 4 on an 11-point numerical rating scale), in failure to non-opioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs). Patients with neuropathic pain were excluded. The co-primary endpoints were mean PI at 3 months (M3) and number of potentially treatment-related adverse events (TRAEs). Secondary outcomes included Western Ontario MAC Master University function subscale (range, 0–68), additional pain and quality of life measures, and responder rates.Results:The non-inferiority of W-TENS was demonstrated in both the per protocol (PP) and intent-to-treat (ITT) populations. At M3, PI in PP population was 3.87 (2.12) compared with 4.66 (2.37) [delta: −0.79 (0.44); 95% CI (−1.65, 0.08)] in W-TENS and WO groups, respectively. A planned superiority analysis showed a significant superiority of W-TENS over WO on PI at M3 (p = 0.0124). The number of TRAEs was significantly lower in the W-TENS group (n = 7) than in the WO group (n = 36) (p < 0.001). Other secondary outcomes also favored W-TENS.Conclusion:W-TENS was more effective and better tolerated than WO in the treatment of chronic nociceptive KOA pain and offers an interesting non-pharmacological analgesic alternative in the management of KOA.Trial Registration: ClinicalTrials.gov: NCT03902340
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-01-19T05:00:38Z
      DOI: 10.1177/1759720X211066233
      Issue No: Vol. 14 (2022)
       
  • Clinical effectiveness of symptomatic therapy compared with standard
           step-up care for the treatment of low-impact psoriatic oligoarthritis: the
           two-arm parallel group randomised POISE feasibility study

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      Authors: Ines Rombach, Laura Tucker, William Tillett, Deepak Jadon, Marion Watson, Anne Francis, Yvonne Sinomati, Susan J Dutton, Laura C Coates
      Abstract: Therapeutic Advances in Musculoskeletal Disease, Volume 14, Issue , January-December 2022.
      Introduction:In psoriatic arthritis (PsA), treatment recommendations support first-line use of disease-modifying antirheumatic drugs (DMARDs). There are few treatment strategy trials, and no previous studies have investigated tailored treatment choice by disease severity. Studies in oligoarthritis (
      Citation: Therapeutic Advances in Musculoskeletal Disease
      PubDate: 2022-01-11T06:00:07Z
      DOI: 10.1177/1759720X211057668
      Issue No: Vol. 14 (2022)
       
 
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