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

BACKGROUND: For a decade, anti-Interleukin 5/Receptor alpha (IL5/Rα) has been available for severe asthma, with marked reductions in exacerbation rates and maintenance oral corticosteroid (mOCS) burden. However, little is known about the long-term, real-world sustained remission. We aimed to assess the stability of response to anti-IL5/Rα over five years.

METHODS: All Danish adults initiating anti-IL5/Rα for severe asthma during JAN2016-JUL2020 were included. Five-domain remission (no exacerbations, no mOCS, FEV1>80%, ACQ<1.5 nor switch to non-anti-IL5/Rα) was assessed annually for five years.

RESULTS: In total, 482 patients were included (median age 56, 48% female). At baseline, 13.9% fulfilled the criteria of no exacerbations, 66.0% of no mOCS, 29.7% of FEV1>80%, and 26.5% of ACQ<1.5. At year five, 18.7% had switched to a non-anti-IL5/Rα biologic.The overall remission rate was 17.6-23.1% over five 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 one year of remission was achieved by 37.4% of patients, with some patients first achieving remission during year two or three.Only 7.7% achieved sustained five-year remission. Failure to achieve remission was driven by permanently impaired FEV1 and persistent uncontrolled symptoms. Five-year sustained freedom from exacerbations and mOCS 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 five years. Remission is a dynamic state with intermittent relapses, and sustained long-term remission is rare using current domains.