The relative efficacy of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that directly depletes eosinophils 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% confidence interval [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 prebronchodilator forced expiratory volume in 1 second 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 efficacies of treatments from trials with heterogeneous patient populations. When baseline patient characteristics were matched across asthma trials, benralizumab and mepolizumab yielded similar efficacy.