Long-term efficacy but rare sustained remission: individual-level 5-year stability in anti-IL5/Rα biologic therapy response for severe asthma

Background For a decade, anti-interleukin-5/receptor α (IL5/Rα) has been available to treat severe asthma, with marked reductions in exacerbation rates and maintenance oral corticosteroid burden. However, little is known about long-term, real-world sustained remission. We aimed to assess the stability of response to anti-IL5/Rα over 5 years. Methods All Danish adults initiating anti-IL5/Rα for severe asthma during January 2016 through June 2020 were included. Five-domain remission (no exacerbations, no maintenance oral corticosteroid, forced expiratory volume in 1 s (FEV 1 ) >80% predicted, Asthma Control Questionnaire score <1.5 and no switch to non-anti-IL5/Rα) was assessed annually for 5 years. Results In total, 482 patients were included (median age 56 years, 48% female). At baseline, 13.9% fulfilled the criteria of no exacerbations, 66.0% of no maintenance oral corticosteroid, 29.7% of FEV 1 >80% predicted and 26.5% of Asthma Control Questionnaire score <1.5. At year 5, 18.7% had switched to a non-anti-IL5/Rα biologic. The overall remission rate was 17.6–23.1% over 5 years. However, remission was found to be dynamic; approximately 15.2% of patients in remission per annum did not fulfil the remission criteria the subsequent year. At least 1 year of remission was achieved by 37.4% of patients, with some patients first achieving remission during year 2 or 3. Only 7.7% achieved sustained 5-year remission. Failure to achieve remission was driven by permanently impaired FEV 1 and persistent uncontrolled symptoms. 5-year sustained freedom from exacerbations and maintenance oral corticosteroid use was seen in 33.6% of patients. Conclusions Patients with severe asthma respond well to anti-IL5/Rα, with substantial improvements across all domains over 5 years. Remission is a dynamic state with intermittent relapses, and sustained long-term remission is rare using current domains.