This overview of 17 systematic reviews (including network meta-analyses) synthesized indirect comparative evidence on the efficacy and safety of six biologic agents—omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab—for uncontrolled moderate-to-severe asthma in patients aged ≥12 years, across outcomes including annualized exacerbation rate (AER), FEV1, ACQ, AQLQ, oral corticosteroid (OCS) reduction, and serious adverse events (SAEs).
In indirect comparisons, dupilumab outperformed benralizumab (RR=0.46), mepolizumab (RR=0.72), and reslizumab (RR=0.62) on AER in the general severe asthma population; tezepelumab was favored over benralizumab (RR=0.73). In eosinophilic subgroups, dupilumab and tezepelumab were consistently favorable at ≥150 and ≥300 cells/μL, while tezepelumab outperformed dupilumab at <150 cells/μL. Dupilumab showed the greatest FEV1 improvement; mepolizumab was favored for ACQ control; omalizumab (general) and tezepelumab (eosinophilic ≥150 cells/μL) were favored for AQLQ. For OCS reduction, benralizumab and dupilumab outperformed reslizumab and tezepelumab. One indirect comparison suggested fewer SAEs with mepolizumab vs. dupilumab (OR=0.65). However, 12 of 17 included reviews were rated critically low quality by AMSTAR 2.
- Nearly all findings are from indirect (network) comparisons; no head-to-head RCTs were available. - 12 of 17 included systematic reviews were rated critically low methodological quality (AMSTAR 2), mainly due to absent protocol registration, incomplete search strategies, and no duplicate data extraction. - Potential overlap of primary trials across included reviews was not formally quantified (no corrected covered area analysis), risking duplication of evidence.
Biomarker-guided biologic selection remains key: dupilumab and tezepelumab appear broadly favorable for exacerbation reduction and lung function, while mepolizumab may offer better symptom control and a safer SAE profile in specific eosinophilic subgroups—but these are indirect comparisons from mostly low-quality reviews and should not be used to establish definitive treatment rankings. Clinicians should individualize biologic choice based on eosinophil count, OCS dependence, and patient profile while awaiting direct head-to-head trial data.
Explore related topics
