Planned Biologic Discontinuation in Severe Asthma: A Systematic Review and Meta-Analysis

Biologic agents targeting IgE, IL-5/IL-5Rα, IL-4Rα, and TSLP have transformed severe asthma outcomes. Whether planned discontinuation of biologics after achieving sustained asthma control is safe and feasible remains unresolved. MEDLINE, Embase, and Cochrane (inception to June 2026); reference lists were hand-searched. RCTs and observational cohort studies enrolling patients (≥12 years) with severe asthma who achieved sustained control on an approved biologic (≥12 months) before planned discontinuation/tapering; non-response-driven discontinuation and studies with ≤10 participants were excluded. Primary outcome: uncontrolled asthma or exacerbation within 12 months; secondary outcomes included symptom scores, lung function, biomarker rebound, and resumption rate of biologics. Twenty-three studies were included (3 RCTs [n = 897], 2 non-randomized comparator cohorts [n = 77], 17 single-arm cohorts, 1 mixed-biologic registry [n = 118]). Two randomized withdrawal trials, XPORT (omalizumab; risk ratio [RR] 1.59; 95% CI, 1.11–2.27) and COMET (mepolizumab; RR 1.29; 95% CI, 1.03–1.61), yielded a pooled RR of 1.36 (95% CI, 1.13–1.65; I2=0%; moderate certainty). An exploratory pool adding DESTINATION (tezepelumab; RR 1.22; 95% CI, 0.88–1.68; non-equivalent comparator) yielded RR 1.32 (95% CI, 1.13–1.56). No eligible dupilumab or reslizumab study was identified. Biomarker rebound followed class-specific kinetics; baseline eosinophilia ≥300 cells/μL and exacerbation burden predicted relapse, with no withdrawal syndrome. Biologic discontinuation in severe asthma carries a moderate-certainty increased exacerbation risk. Because universal de-escalation criteria cannot yet be defined, decisions should be individualized, guided by eosinophil count, exacerbation history, remission duration, and biomarker trajectory, until prospective trial data become available. PROSPERO: CRD420261440934.