Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach

In severe asthma with type 2 (T2) inflammation, biologics targeting key mediators of T2 inflammation, including interleukin (IL)-5, IL-4/IL-13, and immunoglobulin (Ig)E, remarkably improve the management of severe asthma, providing new insights into the clinical course of asthma such as disease modification and broad modulation of T2 inflammation. Once severe asthma has become a "controllable" condition, the question of discontinuation of biologics arises due to cost and side effects. The studies on discontinuing biologics in asthma demonstrate that some of patients successfully discontinue biologics, indicating that it is a feasible option in a subset of patients. Incorporating the evidence of discontinuation, we propose the criteria for the discontinuation of biologics. Our proposed criteria for the discontinuation of biologics consist of an absence of asthma symptoms (asthma control questionnaire [ACQ] score < 1.5 or asthma control test [ACT] score > 19), no asthma exacerbations, no use of oral corticosteroids, normalized spirometry (forced exhaled volume in 1 second [FEV₁] ≥ 80%), suppressed T2 inflammation (blood eosinophil counts < 300 μL and fractional exhaled nitric oxide [FeNO] < 50 ppb), and control of asthma comorbidities. Real-world evidence verified a subset of patients achieving highly well-controlled conditions after use of biologics, namely super-responders, who are candidates for the discontinuation of biologics. If super-responders meet all of the criteria, they are allowed to discontinue biological therapies. Our proposed algorithm may support physicians' treatment decisions for patients receiving biologics.