The journal of allergy and clinical immunology. In practice · 2026
Second-line dupilumab after anti-IL5/Rα failure: remission rates and clinical outcomes in severe asthma.
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Hansen Susanne, Julius Håkansson Kjell Erik, Soendergaard Marianne Baastrup, Sverrild Asger, von Bülow Anna, Hilberg Ole, Silberbrandt Alexander, Johansson Sofie Lock, Dongo Lycely, Vijdea Roxana, Rasmussen Linda Makowska, Schmid Johannes Martin, Ulrik Charlotte Suppli, Bjerrum Anne Sofie, Porsbjerg Celeste
Аннотация
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.
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.