Severe Asthma Biologics Ultra-Precision — Living Meta-Analysis (RapidMeta)

Abstract

Do trials of severe-asthma biologics yield a clinically meaningful reduction in exacerbations? The RapidMeta clinical-medicine living review uses a browser-based, auditable workflow to combine six placebo-controlled phase-3 randomised trials - EXTRA (omalizumab), MENSA (mepolizumab), SIROCCO (benralizumab), Study 3082 (reslizumab), QUEST (dupilumab), and NAVIGATOR (tezepelumab). Each trial's published annualised exacerbation rate ratio was pooled by generic inverse-variance random-effects (REML) on the log scale, with a Hartung-Knapp-Sidik-Jonkman-adjusted interval and a t-based prediction interval. The pooled rate ratio was 0.52 (95% CI 0.44 to 0.62), an approximately 48% reduction in exacerbations. Between-study heterogeneity was moderate-to-substantial (I2 = 69%, Cochran's Q(5) = 16.2, p = 0.007, tau2 = 0.03), reflecting differing mechanisms and eosinophil-defined populations, yet the entire 95% prediction interval (0.32 to 0.85) remained below one. Results are registered into a reproducibility capsule containing a machine-readable config, an interactive reader, and a Vancouver reference pack. Trials are pooled at heterogeneous primary endpoints, doses, and biomarker thresholds, so the pooled estimate is a class-level summary rather than a head-to-head comparison, and cannot substitute for adjudicated trial-level review of risk of bias, switched endpoints, or missing subgroup data.