Second-line dupilumab after anti-IL5/Rα failure: remission rates and clinical outcomes in severe asthma.

BACKGROUND

Switching biologic therapies occurs in 10-25% of severe asthma patients, yet remission rates after first-line biologic failure remain poorly characterised.

OBJECTIVE

To assess clinical remission after switching from anti-IL5/Rα to anti-IL4/13 therapy following treatment failure.

METHODS

This observational cohort study included all Danish adults with severe asthma switching to second-line anti-IL4/13 after failing to achieve remission on anti-IL5/Rα. Remission at 12 months was assessed by four domains: no exacerbations, no maintenance oral corticosteroid use (mOCS), ACQ-6 ≤1.5, and FEV1 >80% predicted (FEV1%pred).

RESULTS

A total of 173 patients were included (median age 55; 45% female), with 79% switching due to lack of treatment effect. The proportion of patients meeting each remission domain increased progressively from pre-biologic baseline to switching and follow-up. At 12 months, 66%, 75%, 54%, and 39% met the exacerbation, mOCS, ACQ-6, and FEV1%pred criteria, respectively; 17% achieved full four-domain remission. Impaired lung function was the most persistent unmet criterion among non-remitters. Pre-biologic and pre-switch biomarkers did not predict remission, whereas atopic dermatitis (33% vs. 16%, p=0.05) and nasal polyps (75% vs. 49%, p=0.02) were associated with remission, and COPD with non-remission (4% vs. 34%, p=0.003).

CONCLUSION

In severe asthma patients not achieving remission on first-line anti-IL5/Rα, nearly one in five achieved remission after switching to anti-IL4/13, suggesting that interclass switching is an effective strategy for patients with inadequate response. Impaired lung function and absence of broad T2 comorbidity predict a lower likelihood of remission.