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

OBJECTIVE

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.

DATA SOURCES: MEDLINE, Embase, and Cochrane (inception to June 2026); reference lists were hand-searched.

STUDY SELECTION: 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.

RESULTS

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.

CONCLUSION

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.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD420261440934.