Matching-adjusted indirect comparison of benralizumabversusinterleukin-5 inhibitors for the treatment of severe asthma: a systematic review

Abstract

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that directly depletes eosinophils. Its relative efficacy versus other IL-5-targeted treatments for patients with severe, uncontrolled asthma is not yet fully characterised.We performed a matching-adjusted indirect comparison (MAIC) of benralizumab versus mepolizumab and reslizumab. Trials were selected through systematic review and evaluation of trial methods. Benralizumab patient-level data were weighted to match treatment-effect-modifying patient characteristics of comparator trials before indirect efficacy comparisons.After matching adjustment, benralizumab and mepolizumab reduced exacerbations versus placebo by 52% and 49%, respectively (rate ratio [RR] 0.94, 95% CI 0.78–1.13; n=1524) and reduced the rate of exacerbations requiring hospitalisation/emergency department visit by 52% and 52%, respectively (RR 1.00, 95% CI 0.57–1.75; n=1524). Benralizumab and mepolizumab similarly improved pre-bronchodilator forced expiratory volume in 1 s at 32 weeks (difference 0.03 L, 95% CI −0.06–0.12; n=1443). Benralizumab and reslizumab patient populations were too dissimilar to generate a sufficient effective sample size to produce a reliable estimate for MAIC.MAIC is a robust way to indirectly compare treatment efficacies from trials with heterogeneous patient populations. When baseline patient characteristics were matched across asthma trials, benralizumab and mepolizumab yielded similar efficacy.

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

“…Moreover, one of the key clinical trials used to register mepolizumab was omitted from the analysis. These findings could not be replicated through MAIC analysis . ITC and network meta‐analysis also allow indirect comparisons and have better statistical power than MAIC, but they may use nonhomogenous populations and introduce bias.…”

“…These results extend our previous baseline‐adjusted analysis of the Phase III benralizumab and mepolizumab exacerbation studies. In those studies, reduction in asthma exacerbation rates was similar for both treatments, and improvements in FEV 1 were numerically greater with benralizumab, but the differences were not statistically significant . Similarly, we conducted MAIC analysis of results from the pivotal Phase III benralizumab trials with exacerbation reduction as the primary end‐point (SIROCCO and CALIMA) vs. the Phase III exacerbation trial of dupilumab (LIBERTY ASTHMA QUEST) (data not provided).…”

“…Matching variables were selected for their clinical and statistical importance in explaining variability in the outcomes of interest and their demonstrated imbalance between ZONDA and SIRIUS or LIBERTY ASTHMA VENTURE. Success of weighting techniques was assessed by comparing adjusted baseline characteristics for patients in ZONDA with characteristics of populations from SIRIUS and LIBERTY ASTHMA VENTURE …”

“…In our recent MAIC analysis of studies identified by a systematic literature review, benralizumab and mepolizumab were comparable for reduction of annual asthma exacerbation rates after weighted adjustment of baseline population characteristics. Benralizumab had a slightly greater effect on forced expiratory volume in 1 second (FEV 1 ), but this was not statistically significant at all time‐points …”

“…Indirect treatment comparison (ITC) via matching‐adjusted indirect comparison (MAIC) allows for comparison of treatments across clinical trials . MAIC is an accepted methodology that has been used to compare biologics for multiple sclerosis, psoriasis, haemophilia, multiple myeloma, and asthma . In our recent MAIC analysis of studies identified by a systematic literature review, benralizumab and mepolizumab were comparable for reduction of annual asthma exacerbation rates after weighted adjustment of baseline population characteristics.…”