Comparative Effectiveness of Mepolizumab and Omalizumab in Severe Asthma: An Indirect Comparison

Rationale: Mepolizumab, a novel anti-IL5 monoclonal Antibody (mAb), and omalizumab, an anti-IgE mAb, target different phenotypes of severe asthma. Some patients will be eligible for both treatments. No head-to-head comparison exists. This study assessed the comparative effectiveness of mepolizumab (100mg fixed-dose subcutaneous injection) and omalizumab (licensed dose range per IgE level/weight), in addition to standard of care, in severe asthma via an indirect comparison.

Methods: A systematic literature review and Bayesian network meta-analysis were performed (GSK ID 200227/H0-13-9058). Included studies were double-blind randomized controlled clinical trials (RCTs) ≥12 weeks’ in duration among severe asthma patients ≥12 years old, with a documented exacerbation history and receiving high-dose inhaled corticosteroids plus ≥1 additional controller. Two populations were examined: subjects potentially eligible for (1) both mAbs (2) either mAb.

Results: (1) 561 and (2) 1,652 subjects were included. Both treatments reduced the rate of clinically significant exacerbations versus placebo. Further, mepolizumab was associated with a reduction in clinically significant exacerbations versus omalizumab, in both populations: (1) Rate ratio [RR]: 0.66; 95% Credible Interval [CrI]: 0.37, 1.19; (2) RR: 0.63; 95% CrI: 0.45, 0.89. The probabilities in each population that mepolizumab was ranked first for treatment effect were (1) 91.6% and (2) 99.6%; the corresponding probabilities for omalizumab were (1) 8.4% and (2) 0.4%.

Conclusions: An indirect comparison versus omalizumab found trends in favor of mepolizumab in reducing the rate of clinically significant exacerbation among treatment-eligible severe asthma patients. Funding: GSK (HO-13-9058)