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- A Cost-effectiveness Analysis of iGlarLixi Versus IDegAsp and Appropriate
Price Exploration of iGlarLixi for Type 2 Diabetes Mellitus Patients in
China-
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Abstract: Background and Objective The efficacy and safety of iGlarLixi, a fixed-ratio combination (FRC) of basal insulin glargine plus lixisenatide, have been demonstrated in type 2 diabetes mellitus (T2DM) patients. However, no relevant economic analysis of iGlarLixi has been done in China. Thus, the primary objective of this study is to evaluate the cost effectiveness of iGlarLixi versus IDegAsp in Chinese T2DM patients, and then back-calculate the appropriate drug price of iGlarLixi to support its pricing after listing in China. Methods The United Kingdom Prospective Diabetes Study Outcome Model 2 (UKPDS OM2) was applied to estimate lifetime health and economic outcomes from the Chinese health-care system perspective. As no head-to-head comparison data are currently available, the baseline cohort characteristics and the initial clinical data for iGlarLixi were derived from the randomized LixiLan-L-China trial. The relative treatment effects for IDegAsp were based on an indirect treatment comparison. Due to the unavailability of iGlarLixi pricing data, the annual medication cost of iGlarLixi was assumed to be equal to that of IDegAsp at the beginning of the study. Afterwards, a break-even analysis using comparator drug price and the willingness-to-pay (WTP) threshold was performed to back-calculate the appropriate drug price of iGlarLixi. One-way sensitivity analysis, scenario analysis and probabilistic sensitivity analysis (PSA) were conducted to assess the robustness of the model. Results Based on the initial assumption of equal annual medication cost of iGlarLixi and IDegAsp, iGlarLixi was cost effective compared to IDegAsp with an incremental cost-effectiveness ratio (ICER) far below the WTP threshold in Chinese T2DM patients. From the back calculation for the price of iGlarLixi, the annual medication cost of iGlarLixi was $656.96 and $1075.96 to obtain an ICER of iGlarLixi versus IDegAsp close to 1 × GDP and 3 × GDP, respectively. When the discount rate was changed from the base value to 8% (the most sensitive parameter to the model results in one-way sensitivity analysis), the ICER was nearly equal to 1 × GDP and 3 × GDP with the annual medication cost of iGlarLixi decreasing to $590.41 and $865.03, respectively. Thus, iGlarLixi was dominant over IDegAsp with an annual medication cost of $590.41 to $865.03. The findings were robust to one-way sensitivity analysis, PSA and scenario analysis. Conclusion This long-term cost-effectiveness analysis in Chinese T2DM patients indicates that iGlarLixi, assuming equal price to IDegAsp, is cost-effective versus IDegAsp with an ICER far below the WTP threshold. With 1 × GDP and 3 × GDP threshold set we back-calculate the appropriate annual medication cost of iGlarLixi to be $590.41 to $865.03, respectively.
PubDate: 2023-03-21
- Vericiguat for the Treatment of Heart Failure with Reduced Ejection
Fraction Following a Worsening Heart Failure Event: A Cost-Effectiveness
Analysis from the Perspective of Chinese Healthcare Providers-
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Abstract: Background and Objective Approximately 38 million people worldwide experience heart failure (HF), with more than 10 million in China. Heart failure exacerbations are the main cause of HF hospitalization, and hospitalizations are the main driver of HF-associated costs. Vericiguat is recommended to treat patients who have had worsening HF despite guideline-directed medical therapy. However, the cost effectiveness of adding vericiguat to the standard treatment of this population in China remains unclear. The objective of this study was to investigate the cost effectiveness of adding vericiguat to standard treatment in patients with HF in the Chinese population Methods A lifetime Markov model with a 1-month cycle length was developed to compare the cost effectiveness of vericiguat plus standard treatment versus standard treatment alone in Chinese patients with HF with reduced ejection fraction following an HF exacerbation, from the perspective of Chinese healthcare providers. The clinical data were obtained from the VICTORIA study. The cost was accessed from our institution or studies conducted in China. The primary outcome was the incremental cost-effectiveness ratio, representing incremental cost per incremental quality-adjusted life-year (QALY). Vericiguat was considered highly cost effective if the incremental cost-effectiveness ratio obtained was lower than 12,551 USD/QALY, cost effective if the incremental cost-effectiveness ratio was between 12,551 and 37,654.5 USD/QALY, and not cost effective if the incremental cost-effectiveness ratio was higher than 37,654.5 USD/QALY. A scenario analysis, one-way sensitivity analysis, and probabilistic sensitivity analysis were performed to test the robustness of the results. Results For a 67-year-old patient with HF following an HF exacerbation, the lifetime cost was 17,721 USD if vericiguat plus standard treatment was given, compared to 7907 USD if standard treatment alone was prescribed. The corresponding effectiveness was 2.20 QALY and 2.10 QALY, respectively. The incremental cost-effectiveness ratio of vericiguat plus standard treatment versus standard treatment alone in Chinese patients with HF was 89,429 USD/QALY, higher than the willingness-to-pay threshold of 37654.5 USD/QALY. The scenario analysis and sensitivity analysis showed the robustness of our results. Conclusions The addition of vericiguat to the treatment regimen of Chinese patients with HF with reduced ejection fraction following an HF exacerbation resulted in an incremental cost-effectiveness ratio of $89,429 USD/QALY compared to standard treatment. This incremental cost-effectiveness ratio exceeds the willingness-to-pay threshold and thus, vericiguat was deemed not cost effective in the Chinese population.
PubDate: 2023-03-16
- Does Therapeutic Repurposing in Cancer Meet the Expectations of Having
Drugs at a Lower Price'-
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Abstract: Abstract Therapeutic repurposing emerged as an alternative to the traditional drug discovery and development model (DDD) of new molecular entities (NMEs). It was anticipated that by being faster, safer, and cheaper, the development would result in lower-cost drugs. As defined in this work, a repurposed cancer drug is one approved by a health regulatory authority against a non-cancer indication that then gains new approval for cancer. With this definition, only three drugs are repurposed for cancer: Bacillus Calmette–Guerin (BCG) vaccine (superficial bladder cancer, thalidomide [multiple myeloma], and propranolol [infantile hemangioma]). Each of these has a different history regarding price and affordability, and it is not yet possible to generalize the impact of drug repurposing on the final price to the patient. However, the development, including the price, does not differ significantly from an NME. For the end consumer, the product’s price is unrelated to whether it followed the classical development or repurposing. Economic constraints for clinical development, and drug prescription biases for repurposing drugs, are barriers yet to be overcome. The affordability of cancer drugs is a complex issue that varies from country to country. Many alternatives for having affordable drugs have been put forward, however these measures have thus far failed and are, at best, palliative. There are no immediate solutions to the problem of access to cancer drugs. It is necessary to critically analyze the impact of the current drug development model and be creative in implementing new models that genuinely benefit society.
PubDate: 2023-03-08
- A Fatal Case of Bictegravir-Induced Fulminant Hepatic Failure
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PubDate: 2023-03-01
- A Cross-Sectional Study of Tampering in Xtampza ER, an Abuse-Deterrent
Formulation of an Extended-Release Opioid, in a Treatment Center
Population-
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Abstract: Background and Objective While the current landscape of opioid use disorder (OUD) is complicated by the increase in use of non-prescription opioids, prescription opioids continue to be frequently used in non-medical ways. In response to this abuse, pharmaceutical companies have developed abuse deterrent formulations (ADFs) for extended-release (ER) opioids. To test the effectiveness of Xtampza ER ADF (oxycodone myristate) at reducing tampering, its rate of tampering in a treatment-center population was compared to immediate release (IR) single entity (SE) oxycodone, other ER oxycodone opioids, and ER oxymorphone. Methods Data were collected between the third quarter of 2018 and the third quarter of 2021 from individuals entering nationally distributed opioid treatment programs. To determine odds of tampering with Xtampza ER compared to each comparator, a logistic model was fit with a random intercept allowing for multiple drugs in each subject. Within-subject correlation was assumed to have a compound symmetric relationship. Results Overlap among the categories of drug tampering was high. Logistic regression analyses found that oxycodone myristate had lower odds of tampering when compared to both IR SE oxycodone (OR = 0.23 [95% CI 0.11, 0.50], p = 0.0002) and ER oxymorphone (OR = 0.30 [95% CI 0.14, 0.67], p = 0.0038). Oxycodone myristate was not significantly different from other ER oxycodone opioids (OR = 0.5 [95% CI 0.24, 1.03], p = 0.0612). These findings did not change when the estimates were adjusted for age and sex. Conclusions Drugs employing ADF technology may reduce the likelihood of tampering when compared to non-ADF formulations in a treatment-center population, which represents an opportunity for intervention in OUD among those still requiring pain management.
PubDate: 2023-03-01
- Comparison of Real-World Costs, Healthcare Resource Utilization, and
Comorbidity-Related Costs Between Ixekizumab and Secukinumab Among
Biologic-Experienced Patients with Psoriasis Over 18 Months in the USA-
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Abstract: Background and Objective Data on real-world healthcare costs for ixekizumab (IXE) and secukinumab (SEC) in biologic-experienced patients with psoriasis are limited. This study compared real-world costs and healthcare resource utilization between IXE and SEC in biologic-experienced patients with psoriasis over an 18-month follow-up period in the USA. Methods Adult patients with a diagnosis of psoriasis between 1 March, 2015 and 31 October, 2019 were identified using health insurance claims data from IBM Watson Health MarketScan®. The index date was the date of the first IXE or SEC claim. Biologic-experienced patients with one or more pre-period claims for biologic drugs were identified. Inverse probability of treatment weighting was used to reduce cohort imbalances. All-cause and psoriasis-related direct healthcare costs along with index drug costs were estimated during the follow-up and reported as per patient per month. Discount factors published by the Institute for Clinical and Economic Review were applied to psoriasis-related biologics to adjust pharmacy costs. Results A total of 411 IXE and 780 SEC users were included. After weighting, all-cause inpatient admissions were similar between IXE (9.5%) and SEC users (10.3%). Weighted, mean ± standard deviation per patient per month all-cause healthcare costs were higher in IXE users ($6670 ± $2910) than in SEC users ($6239 ± $3903; p = 0.049). Psoriasis-related and monthly index drug costs were higher in IXE users ($5609 ± $2009; p < 0.001 and $4688 ± $1994; p < 0.001, respectively) than in SEC users ($5095 ± $2291 and $3853 ± $1977, respectively). After Institute for Clinical and Economic Review adjustment, mean per patient per month all-cause ($4363 ± $2576 vs $4398 ± $3517) and psoriasis-related costs ($3302 ± $1264 vs $3253 ± $1504) were similar between the groups. Institute for Clinical and Economic Review- and adherence-adjusted mean per patient per month index drug costs were similar between IXE and SEC users (p = 0.339). Conclusions Institute for Clinical and Economic Review-adjusted all-cause and psoriasis-related costs were comparable between IXE and SEC users among biologic-experienced patients over an 18-month follow-up period.
PubDate: 2023-02-25
- Evaluation of Cardiac Adverse Events with Nivolumab Using a Japanese
Real-World Database-
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Abstract: Background Nivolumab has been used for the treatment of various types of cancers and has achieved improvements in overall survival. However, nivolumab can cause a variety of adverse events (AEs). Among these, cardiac-specific AEs have received little attention in clinical trials, despite their life-threatening potential. Objective The present study aimed to determine the risk of nivolumab-induced cardiac AEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database. Methods We analyzed data for the period between April 2004 and March 2021. Data on cardiac AEs were extracted and relative risk of AEs was estimated using the reporting odds ratio (ROR). Results We analyzed 1,772,494 reports and identified 18,721 reports of AEs caused by nivolumab. Of these, 409 reports involved cardiac AEs. Signals were detected for four cardiac AEs: myocarditis; pericardial effusion; pericarditis; and immune-mediated myocarditis. Among these, myocarditis was the most frequently reported (35.0%) and included fatal cases. A histogram of times to onset showed nivolumab-associated AEs occurring 41–127 days after starting administration, with outlier cases of myocarditis or pericardial effusion occurring after more than one year, both with catastrophic consequences. Conclusion This study focused on cardiac AEs caused by nivolumab as post-marketing AEs. Myocarditis and pericardial effusion have been associated with some fatal cases after administration of nivolumab. Patients should be monitored for signs of onset for these AEs, not only at the start of administration, but also over an extended period after nivolumab administration.
PubDate: 2023-02-13
- A Single- and Multiple-Dose Pharmacokinetic Study of Oral Perampanel in
Healthy Chinese Subjects-
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Abstract: Background and Objective Perampanel is a once-daily oral anti-seizure medication indicated for focal-onset seizures and generalized tonic-clonic seizures. This study investigated the single- and multiple-dose pharmacokinetics of perampanel in healthy Chinese adults. Methods Study 052 (NCT03424564) was a phase I, single-center, open-label, parallel-group study. In the single-dose part of the study, subjects received a single oral dose of perampanel 2, 4, or 8 mg. In the multiple-dose part, subjects received once-daily oral perampanel 2 mg on Days 1–7 and 4 mg on Days 8–21. Pharmacokinetic parameters were determined from perampanel plasma concentrations using non-compartmental analysis. Dose proportionality after single doses of perampanel was assessed. Safety and tolerability were evaluated. Results In the single-dose part (N = 30), median time to reach maximum concentration (tmax) was 0.75–1.0 h, mean terminal elimination phase half-life (t½) was 85.6–122 h, mean maximum observed concentration (Cmax) was 77.9–276 ng/mL, and mean area under the concentration–time curve from time zero to time of the last quantifiable concentration (AUC(0-t)) was 4070–15100 ng·h/mL. Single-dose pharmacokinetics were linear for perampanel 2–8 mg. In the multiple-dose part (N = 12), Day 21 steady-state (4 mg/day) parameters were median time at which the highest drug concentration occurs at steady state (tss,max), 1.25 h; mean t½, 109 h; mean maximum observed concentration at steady state (Css,max), 453 ng/mL; and mean area under the concentration–time curve over the dosing interval on multiple dosing (AUC(0- τ)), 7540 ng·h/mL. For single- and multiple-dose perampanel, the most common treatment-emergent adverse events were dizziness and somnolence. Conclusions Single- and multiple-dose pharmacokinetics of perampanel in healthy Chinese adults revealed rapid perampanel absorption, slow elimination, and a linear relationship with single perampanel doses of 2–8 mg. Findings were consistent with previous studies of perampanel pharmacokinetics in other ethnic/racial populations of healthy subjects. Single and multiple doses of perampanel were generally safe and well tolerated. Clinical Trial Registration NCT03424564; registered February 2018.
PubDate: 2023-02-06
- Adherence to Adjuvant Endocrine Therapy and Survival Among Older Women
with Early-Stage Hormone Receptor-Positive Breast Cancer-
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Abstract: Background and Objective Although improving adherence to adjuvant endocrine therapies (AETs) is critical to ensure better patient outcomes, the evidence is still lacking on differences in 5-year AET adherence trajectories. This study aimed to estimate the time trend of adherence by the type of individual AET and the association of adherence to AETs with overall survival among older women with hormone receptor-positive breast cancer. Methods This study used the Surveillance, Epidemiology, and End Results-Medicare database 2006–2016. We included women aged ≥ 65 years with newly diagnosed hormone receptor-positive breast cancer and who had initiated AET (anastrozole, letrozole, exemestane, or tamoxifen). Adherence to AETs was defined as the proportion of days covered that was calculated for the follow-up period (5 years). The overall survival time was defined as the time from the date of AET initiation to death. The linear mixed models with repeated measures were used to estimate the changes in adherence to AETs. The Cox proportional hazard model was used to assess the relationships (hazard ratio [HR] and 95% confidence interval [CI]) between adherence to AETs and death. Results A total of 11,617 patients were included. Anastrozole was the most commonly used (n = 6,908), followed by letrozole (n = 2,586), tamoxifen (n = 1,750), and exemestane (n = 373). The mean (standard deviation) of proportion of days covered for 5 years was 57.4 (34.6), indicating the highest proportion of days covered in the anastrozole group [61.1 (34.1)] and the lowest proportion of days covered in the exemestane group [44.0 (35.1)]. Overall, adherence to AET decreased over the 5-year follow-up period in all AET groups, but the decrease in the tamoxifen group was steeper (42.3% decreased) compared with other AETs. Anastrozole, letrozole, and exemestane groups were associated with a lower risk of death compared with the tamoxifen group (HR = 0.80, 95% CI 0.71–0.89 for anastrozole; HR = 0.82, 95% CI 0.72–0.93 for letrozole; HR = 0.82, 95% CI 0.63–1.07 for exemestane). Conclusions Patients who initiated with tamoxifen had a steeper decrease in adherence over the 5 years compared with anastrozole, letrozole, and exemestane groups. Furthermore, higher adherence was associated with a decreased risk of mortality. Physicians should be cognizant of decreasing adherence over time and choose effective treatment options with minimal side-effect profiles to better support adherence by patients with breast cancer.
PubDate: 2023-02-06
- Use of Methotrexate in Girls and Women of Childbearing Age, Occurrence of
Methotrexate-Exposed Pregnancies and Their Outcomes in Germany: A Claims
Data Analysis-
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Abstract: Background and Objective Methotrexate should be withdrawn before pregnancy because of its teratogenic potential. We aimed to describe the use of methotrexate in women of childbearing age in Germany and the occurrence and outcomes of pregnancies exposed to methotrexate. Methods Using the German Pharmacoepidemiological Research Database (GePaRD, covering ~ 20% of the German population), we determined the age-specific and age-standardized prevalence of methotrexate use for each year between 2004 and 2019 among women aged 13–49 years (cross-sectional analyses). In a cohort analysis, we assessed the number and outcomes of pregnancies exposed to methotrexate in the critical time window. Exposure was defined as a dispensation overlapping with the onset of pregnancy or a dispensation in the first 8 weeks of pregnancy. For children born from exposed pregnancies, the mother’s and children’s data were linked and the occurrence of malformations was assessed by reviewing all available data of these children. Results The age-standardized prevalence of methotrexate use per 1000 females increased from 1.5 in 2004 to 2.3 in 2019, i.e., by 52%. Overall, we identified 184 pregnancies exposed to methotrexate. Of these, 53% ended in a live birth (21% preterm) and 11% in an induced abortion. Among 81 live-born children linked to their mothers, five children (6%) had relevant malformations including congenital heart defects and musculoskeletal malformations. Conclusions In Germany, the use of methotrexate in women of childbearing age has substantially increased since 2004. Despite the known teratogenic effect, there was a considerable number of exposed pregnancies. Also, malformations likely associated with methotrexate and thus avoidable were observed.
PubDate: 2023-02-01
- Correction to: Nonmetastatic Castration‑Resistant Prostate Cancer:
Current Challenges and Trends-
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PubDate: 2023-01-27
- Comment on: “Efficacy and Safety of Saroglitazar in Patients with
Cardiometabolic Diseases: A Systematic Review and Meta-Analysis of
Randomized Controlled Trials”-
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PubDate: 2023-01-13
- Comparison of Adverse Events Occurred During Administration of Dipeptidyl
Peptidase-4 Inhibitor in Patients with Diabetes Using FDA Adverse Event
Reporting System-
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Abstract: Background and Objective Various dipeptidyl peptidase-4 (DPP-4) inhibitors have been approved for the treatment of diabetes. The frequencies of known serious side effects might differ among DPP-4 inhibitors, therefore a large sample size is needed to study them in prospective clinical trials. We examined the adverse events that occurred during the administration of a DPP-4 inhibitor in patients with diabetes using FDA Adverse Event Reporting System (FAERS) data. Methods We used FAERS data reported between January 2013 and March 2022 in patients with diabetes who received a DPP-4 inhibitor. Statistical analyses were conducted to calculate reporting odds ratio (ROR) and adjusted ROR (aROR) controlling for differences in patient background. Results The 9 target DPP-4 inhibitors were sitagliptin (N = 26,843), vildagliptin (N = 4767), alogliptin (N = 2085), linagliptin (N = 7969), saxagliptin (N = 3334), teneligliptin (N = 461), anagliptin (N = 102), trelagliptin (N = 17), and omarigliptin (N = 12). Compared with sitagliptin, aROR of acute kidney injury was significantly < 1.000 for alogliptin (0.247 [95% confidence interval (CI) 0.150–0.408], p < 0.001) but aROR of pemphigoid was significantly > 1.000 for alogliptin (3.082 [95% CI 2.156–4.406], p < 0.001). Similar statistical analyses were conducted for other adverse events and the types of adverse events with aROR of significantly < 1.000 or > 1.000 differed depending on the type of DPP-4 inhibitor. Conclusions Although it is impossible to select a DPP-4 inhibitor with aROR of < 1.000 of all occurrences of adverse events, these results may be used for drug selection when the patient has adverse events that need to be avoided. We provided the sample code of software R that can reproduce the results.
PubDate: 2023-01-13
- Response to Comment on: “Efficacy and Safety of Saroglitazar in Patients
with Cardiometabolic Diseases: A Systematic Review and Meta-Analysis of
Randomized Controlled Trials”-
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PubDate: 2023-01-12
- Pharmacokinetic and Pharmacodynamic Characteristics of Insulin Icodec
After Subcutaneous Administration in the Thigh, Abdomen or Upper Arm in
Individuals with Type 2 Diabetes Mellitus-
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Abstract: Background and Objective Individuals with diabetes mellitus may prefer different body regions for subcutaneous insulin administration. This trial investigated whether choice of injection region affects exposure and glucose-lowering effect of once-weekly basal insulin icodec. Methods In a randomised, open-label, crossover trial, 25 individuals with type 2 diabetes received single subcutaneous icodec injections (5.6 U/kg) in the thigh, abdomen or upper arm (9–13 weeks’ washout). Pharmacokinetic blood sampling occurred frequently until 35 days post-dose. Partial glucose-lowering effect was assessed 36–60 h post-dose in a glucose clamp (target 7.5 mmol/L). Steady-state pharmacokinetics following multiple once-weekly dosing were simulated using a two-compartment pharmacokinetic model. Results Total icodec exposure (area under the curve from zero to infinity after single dose; AUC0–∞,SD) was similar between injection in the thigh, abdomen and upper arm (estimated AUC0–∞,SD ratios [95% confidence interval]: abdomen/thigh 1.02 [0.96–1.09], p = 0.473; upper arm/thigh 1.04 [0.98–1.10], p = 0.162; abdomen/upper arm 0.98 [0.93–1.05], p = 0.610). Maximum icodec concentration (Cmax) after single dose was higher for abdomen (by 17%, p = 0.002) and upper arm (by 24%, p < 0.001) versus thigh. When simulated to steady state, smaller differences in Cmax were seen for abdomen (by 11%, p = 0.004) and upper arm (by 16%, p < 0.001) versus thigh. Geometric mean [coefficient of variation] glucose-lowering effect 36–60 h post-dose was comparable between the thigh (1961 mg/kg [51%]), abdomen (2130 mg/kg [52%]) and upper arm (2391 mg/kg [40%]). Conclusion Icodec can be administered subcutaneously in the thigh, abdomen or upper arm with no clinically relevant difference in exposure and with a similar glucose-lowering effect. ClinicalTrials.gov Identifier NCT04582448.
PubDate: 2023-01-11
- Assessment of Hormonal Contraceptive Utilization and Associated Odds of
Hypercoagulopathy in Patients with Venous Malformations Using a National
Claims Database-
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Abstract: Background Vascular anomalies that exhibit a slow velocity of blood flow, specifically venous malformations (VM), are associated with hypercoagulability. There is limited literature on the utilization of hormonal contraceptives (HCs) and the development of clotting events in female individuals diagnosed with VM. Objective We aimed to characterize HC utilization and associated odds of hypercoagulopathy in patients with VM of child-bearing age. Methods Using a national administrative claims database, we identified female patients with VM aged 15–49 years and a control population, matched for age and length of insurance enrollment, from 2016 to 2021. Multivariable logistic regression was used to estimate the odds of hypercoagulation events associated with HC use. Results Two hundred and sixty-seven (47.2%) patients with VM and 1284 (45.4%) control patients utilized HCs during the study period. Oral contraceptives were the most common HC for patients with and without VM (73.8% and 76.9% of those taking HCs, respectively), and estrogen-containing combination HCs (70.4% in patients with VM and 75.9% in controls) were more prevalent than progestin-only HCs in both populations. Despite a heightened baseline odds of hypercoagulopathy in patients with VM relative to patients without VM (odds ratio = 12.54; 95% confidence interval 7.73–20.3), HC use was not associated with an increased odds of hypercoagulation in the VM subpopulation (odds ratio = 0.82; 95% confidence interval 0.46–1.46). In contrast, tobacco use (odds ratio = 2.12; 95% confidence interval 1.09–4.12) and a history of coagulopathy (odds ratio = 3.92; 95% confidence interval 1.48–10.36) were predictive of thromboembolic events in the VM cohort. Conclusions These findings suggest that patients with VM may safely use HCs with careful consideration of other risk factors for thromboses.
PubDate: 2023-01-10
- Assessing the Reporting of Harms in Systematic Reviews Focused on the
Therapeutic and Cosmetic Uses of Botulinum Toxin-
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Abstract: Background and Objective The expanding use of botulinum toxin (BoNT) in medical practice demonstrates the need to highlight whether there is adequate information regarding its safety profile. The aim of our study was to identify completeness of harms reporting for BoNT treatment within systematic reviews (SRs), assess quality of SRs using the AMSTAR-2 tool, and determine the degree of overlap among primary studies within each SR. Methods On May 31, 2022, we searched Embase, Epistemonikos, MEDLINE, and the Cochrane Database of Systematic Reviews for SRs on BoNT therapy. Screening and data extraction were performed in a masked, duplicate fashion. AMSTAR-2 was used to evaluate the methodological quality of included SRs. Corrected covered area (CCA) was calculated for SR dyads. Results Of the 90 included SRs, we found that 70 completed less than 50% of harms items. The most reported items were BoNT as a favorable intervention (73/90, 81.1%) and harms as a primary outcome (72/90, 80.0%). The least reported items were grades and severity scales used to classify harms (8/90, 8.9%) and number of treatment discontinuations in each arm (10/90, 11.1%). Eighty-three SRs were rated “critically low” (83/90, 92.2%), while 5 SRs were rated “high” (5/90, 5.6%) via AMSTAR-2 tool. Significant associations were found between completion of harms reporting and: (1) a “critically low” appraisal on AMSTAR-2 tool (p = 0.0060) and (2) whether harms was reported as a primary outcome (p = 0.0001). The total CCA overlap was determined to be 0.8%. Conclusion Our results demonstrate that harms are underreported within BoNT SRs. Because healthcare professionals often refer to SRs to guide clinical decision making, it is important to continue to explore shortcomings among BoNT literature in future studies.
PubDate: 2023-01-10
- Cost Effectiveness of Rituximab Therapy for Rheumatoid Arthritis: A
Systematic Review and Meta-Analysis of Cost-Utility Studies-
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Abstract: Background and Objectives Depletion of B cells is shown to be clinically effective for rheumatoid arthritis (RA) treatment. Although B-cell depletion therapy with rituximab is indicated for RA patients who have failed to other disease-modifying anti-rheumatic drugs (DMARDs), primary cost-effectiveness evidence is inconsistent. We aimed to provide synthesised cost-effectiveness evidence of rituximab in the treatment of RA compared to other DMARDs, since the published cost-effectiveness evidence is mixed. Methods We identified economic evaluation studies reporting cost-utility of rituximab compared to other DMARDs by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled incremental net benefit (INB) in (purchasing power parity) adjusted US$ with 95% confidence intervals. We used the modified economic evaluations bias checklist and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) instrument for quality appraisal. The study protocol was pre-registered with PROSPERO, CRD 42021222541. Results Of the selected 18 studies, the majority were from high-income countries (n = 14) followed by upper middle-income countries (n = 3) and lower middle-income countries (n = 1), with minimal risk of bias. Rituximab is significantly cost effective with a pooled INB (95% CI) of $8767 (720 to 16,814). On subgroup analysis, rituximab is significantly cost effective from a health system perspective [$12,832 (3392 to 22,272)], for studies using 3.5% discount rate [$15,468 (5973 to 24,963)] and a for a time horizon of less than 5 years [$8496 (1547 to 15,445)]. In a separate analysis, rituximab as third-line therapy (for conventional synthetic DMARDs followed by any other biologic DMARD failed patients) was not cost effective compared to DMARDs [$5314 (−2278 to 12,905)]. Further, the GRADE assessment indicated very-low confidence in the pooled results. Conclusion Rituximab is cost effective compared to other DMARDs but not if used as third-line therapy after failure of biologics. There is a need to generate context-specific evidence for the lower income settings.
PubDate: 2023-01-09
- Correction to: Cost‑Utility Analysis of Pegaspargase for the Treatment
of Acute Lymphoblastic Leukemia in Greece-
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PubDate: 2022-12-29
- Correction to: Comment on “Efficacy and Safety of Subcutaneous
Esketamine in the Treatment of Suicidality in Major Depressive Disorder
and Bipolar Depression”-
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PubDate: 2022-12-02
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