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Matching-adjusted comparison of oral corticosteroid reduction in asthma: Systematic review of biologics.

ABSTRACT: BACKGROUND:Oral corticosteroid (OCS) treatment for severe asthma is associated with substantial disease burden. Thus, OCS dosage reduction is desirable. Relative efficacy of biologics in reducing OCS treatment for severe, uncontrolled asthma is not fully characterized. OBJECTIVE:We performed a matching-adjusted indirect comparison (MAIC) to assess the relative effects on OCS treatment reduction of three biologic asthma treatments. METHODS:In MAIC of benralizumab vs. mepolizumab and vs. dupilumab, patient-level data from the Phase III benralizumab OCS-sparing trial, ZONDA, were weighted to match treatment effect-modifying patient characteristics in comparator trials. RESULTS:After matching adjustment, mean difference between benralizumab and mepolizumab for OCS reduction was 6.08% (95% CI -22.22-34.38; P = .67) by week 24, and odds ratio of OCS elimination was 2.32 (95% CI 0.48-11.15; P = .29). A trend in annual asthma exacerbation rate reduction favouring benralizumab over mepolizumab was observed, although it was not statistically significant (rate ratio [RR] = 0.56 [95% CI 0.28-1.13; P = .11]). Mean difference between benralizumab and dupilumab for OCS reduction was -0.71% (95% CI -20.56-19.15; P = .94), and odds ratio of OCS elimination was 2.26 (95% CI 0.52-9.84; P = .28). A non-significant trend in annual asthma exacerbation rate reduction favouring benralizumab over dupilumab was observed (RR = 0.50 [95% CI 0.20-1.28; P = .15]). Effective sample size was 49% (72 vs. 148) and 25% (36 vs. 142) of original sample size for MAIC of benralizumab vs. mepolizumab and benralizumab vs. dupilumab, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:Following patient baseline characteristics matching across clinical trials, benralizumab demonstrated efficacy comparable to mepolizumab and dupilumab for OCS dosage reduction, OCS elimination, and annual exacerbation rate reduction. Comparatively low effective sample sizes indicated substantial differences for patient populations between ZONDA and mepolizumab and dupilumab trials.

SUBMITTER: Bourdin A

PROVIDER: S-EPMC7204869 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Matching-adjusted comparison of oral corticosteroid reduction in asthma: Systematic review of biologics.

Bourdin Arnaud A Husereau Don D Molinari Nicolas N Golam Sarowar S Siddiqui Mohd Kashif MK Lindner Leandro L Xu Xiao X

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20200320 4

<h4>Background</h4>Oral corticosteroid (OCS) treatment for severe asthma is associated with substantial disease burden. Thus, OCS dosage reduction is desirable. Relative efficacy of biologics in reducing OCS treatment for severe, uncontrolled asthma is not fully characterized.<h4>Objective</h4>We performed a matching-adjusted indirect comparison (MAIC) to assess the relative effects on OCS treatment reduction of three biologic asthma treatments.<h4>Methods</h4>In MAIC of benralizumab vs. mepoliz ...[more]

PMID: 31943429

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Project description:PurposeThe oral corticosteroid (OCS)-sparing effect of several biologics (BIOs) has been shown in clinical trials. To date, no study has evaluated differences in OCS dose reduction between BIO-initiated and BIO-non-initiated patients in real-world clinical practice. We compared dose reductions in maintenance OCS between BIO-initiated and BIO-non-initiated severe asthma patients in a real-world setting.Patients and methodsThis retrospective cohort study used the data from the Diagnosis Procedure Combination database of Medical Data Vision in Japan. Severe asthma patients with continuous use of OCS were selected from December 2015 to February 2020. The primary endpoint was the proportion reduction in daily maintenance OCS dose from Week 0 to Week 24. Analyses were performed using inverse probability treatment weighting.ResultsIn total, 2927 patients were included (BIO-initiated: 239 patients, BIO-non-initiated: 2688 patients). Adjusted median (quartile [Q] 1-Q3) proportion reduction in daily maintenance OCS dose at Week 24 from the index date was 25.0% (0.0-100.0%) and 0.0% (0.0-83.3%) in the BIO-initiated and BIO-non-initiated groups, respectively (Hodges-Lehmann estimate [95% confidence interval], 0.0000% [0.0000-0.3365%]). Respective proportions of patients in the BIO-initiated and BIO-non-initiated groups achieving dose reductions from the index date in the daily maintenance OCS dose at Week 24 were >0% reduction, 56.6% and 44.1% (odds ratio [OR] 1.6554); ≥25% reduction, 50.5% and 40.6% (OR 1.4888); ≥50% reduction, 42.8% and 33.7% (OR 1.4714); and 100% reduction, 26.2% and 24.4% (OR 1.1005).ConclusionAmong severe asthma patients, the daily dose of maintenance OCS was reduced with BIO treatment. Although a higher percentage of patients in the BIO-initiated group had an OCS reduction of ≤75% than the BIO-non-initiated group, we found no clear difference in OCS reduction. Our findings will be justified by further research that incorporates a longer observation period and variables excluded from this study.Trial registrationClinicalTrials.gov (NCT05136547).

Project description:BackgroundAnchored covariate-adjusted indirect comparisons inform reimbursement decisions where there are no head-to-head trials between the treatments of interest, there is a common comparator arm shared by the studies, and there are patient-level data limitations. Matching-adjusted indirect comparison (MAIC), based on propensity score weighting, is the most widely used covariate-adjusted indirect comparison method in health technology assessment. MAIC has poor precision and is inefficient when the effective sample size after weighting is small.MethodsA modular extension to MAIC, termed two-stage matching-adjusted indirect comparison (2SMAIC), is proposed. This uses two parametric models. One estimates the treatment assignment mechanism in the study with individual patient data (IPD), the other estimates the trial assignment mechanism. The first model produces inverse probability weights that are combined with the odds weights produced by the second model. The resulting weights seek to balance covariates between treatment arms and across studies. A simulation study provides proof-of-principle in an indirect comparison performed across two randomized trials. Nevertheless, 2SMAIC can be applied in situations where the IPD trial is observational, by including potential confounders in the treatment assignment model. The simulation study also explores the use of weight truncation in combination with MAIC for the first time.ResultsDespite enforcing randomization and knowing the true treatment assignment mechanism in the IPD trial, 2SMAIC yields improved precision and efficiency with respect to MAIC in all scenarios, while maintaining similarly low levels of bias. The two-stage approach is effective when sample sizes in the IPD trial are low, as it controls for chance imbalances in prognostic baseline covariates between study arms. It is not as effective when overlap between the trials' target populations is poor and the extremity of the weights is high. In these scenarios, truncation leads to substantial precision and efficiency gains but induces considerable bias. The combination of a two-stage approach with truncation produces the highest precision and efficiency improvements.ConclusionsTwo-stage approaches to MAIC can increase precision and efficiency with respect to the standard approach by adjusting for empirical imbalances in prognostic covariates in the IPD trial. Further modules could be incorporated for additional variance reduction or to account for missingness and non-compliance in the IPD trial.

Project description:ObjectiveTo estimate the level of dispensing of oral corticosteroids (OCS) for managing asthma in Australia, with a particular focus on the cumulative dispensing of doses associated with long term toxicity (≥ 1000 mg prednisolone-equivalent).DesignRetrospective cohort study; analysis of 10% random sample of Pharmaceutical Benefits Scheme (PBS) dispensing data.Participants, settingPeople aged 12 years or more treated for asthma during 2014-2018, according to dispensing of controller inhaled corticosteroids (ICS).Main outcome measuresNumber of people dispensed OCS for managing asthma during 2014-2018; proportion who were cumulatively dispensed at least 1000 mg prednisolone-equivalent. The secondary outcome was the number of people dispensed at least 1000 mg prednisolone-equivalent during 2018, stratified by inhaler controller dose and use.Results124 011 people had been dispensed at least two prescriptions of ICS during 2014-2018 and met the study definition for asthma, of whom 64 112 (51.7%) had also been dispensed OCS, including 34 580 (27.9% of the asthma group) cumulatively dispensed 1000 mg prednisolone-equivalent or more. Of 138 073 people dispensed OCS at this level, 68 077 (49%) were patients with airway diseases. Dispensing of diabetes and osteoporosis medications was more common for people cumulatively dispensed 1000 mg prednisolone-equivalent or more. During 2018, 4633 people with asthma using high dose ICS controllers were dispensed 1000 mg prednisolone-equivalent or more, for 2316 of whom (50%) controller use was inadequate.ConclusionsCumulative exposure to OCS in Australia reaches levels associated with toxicity in one-quarter of patients with asthma using ICS. Cumulative dispensing of potentially toxic OCS amounts often accompanies inadequate inhaler controller dispensing. Better approaches are needed to improve adherence to controller therapy, improve outcomes for people with asthma, and to minimise the use and toxicity of OCS.

Project description:BackgroundFor nonmetastatic castration-resistant prostate cancer (nmCRPC), 3 drugs under patent protection-apalutamide, enzalutamide, and darolutamide-were approved based on randomized, placebo-controlled trials; 1 drug with generic availability, abiraterone acetate, showed efficacy in a single-arm trial and is commonly prescribed. Lacking head-to-head trials, the optimal treatment for nmCRPC is unknown, despite widely varied treatment costs. We compared the efficacy and safety of nmCRPC treatments.MethodsWe searched bibliographic databases, regulatory documents, and trial registries for nmCRPC trials. We included published results and, when available, original data. We performed matching-adjusted indirect comparison and network meta-analysis and compared treatments regarding metastasis-free survival, overall survival, and serious adverse events.ResultsWe analyzed 5 trials with 4360 participants. Compared with placebo, abiraterone acetate engendered the lowest hazard of metastasis and death (hazard ratio [HR] = 0.22, 95% credible interval [CrI] = 0.12-0.41), followed by apalutamide (HR = 0.28, 95% CrI = 0.23-0.34), enzalutamide (HR = 0.30, 95% CrI = 0.25-0.36), and darolutamide (HR = 0.41, 95% CrI = 0.34-0.49); darolutamide led to the lowest hazard of death (HR = 0.69, 95% CrI = 0.53-0.90), followed by enzalutamide (HR = 0.73, 95% CrI = 0.61-0.87) and apalutamide (HR = 0.75, 95% CrI = 0.59-0.95); darolutamide resulted in the lowest odds of serious adverse events (odds ratio [OR] = 1.32, 95% CrI = 1.02-1.70), followed by enzalutamide (OR =1.43, 95% CrI = 1.08-1.89), apalutamide (OR = 1.58, 95% CrI = 1.23-2.03), and abiraterone acetate (OR = 1.94, 95% CrI = 1.17-3.22).ConclusionsFor nmCRPC, darolutamide offered optimal efficacy and safety among approved drugs, and abiraterone acetate may offer comparable metastasis-free survival benefit with cost savings from generic availability. Future research is needed to more fully examine the benefit of abiraterone acetate.

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Matching-adjusted comparison of oral corticosteroid reduction in asthma: Systematic review of biologics.

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Matching-adjusted comparison of oral corticosteroid reduction in asthma: Systematic review of biologics.

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