Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach

Abstract

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 [FEV 1 ] ≥ 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 wellcontrolled 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.

Complete response to anti-interleukin-5 biologics in a real-life setting: results from the nationwide Danish Severe Asthma Register

“…These patients may furthermore potentially fulfil criteria for remission of asthma [ 43 ] and describing their long-term prognosis will be an important future research goal. A further important question is obviously whether these patients would be able to stop or down-titrate their biological treatment [ 44 ] and studies examining this question are urgently needed. These results also highlight the possible importance of timely intervention with biologics in severe asthma in appropriate candidates and further research is needed to consolidate whether earlier initiation of biologics improves the overall prognosis.…”

Dual Effect of Low-Molecular-Weight Bioregulators of Bacterial Origin in Experimental Model of Asthma

“…The results obtained provide a new understanding of the clinical course of asthma and can be used to optimize the regimens for withdrawal from biologics, which are already possible in a certain category of patients [66]. At the same time, low-molecular-weight bioregulators can have an effect both on predictors of the early course of asthma and on markers of the late stages of allergic inflammation during remission, but their use in the acute phase of allergic inflammation will aggravate the severity of asthma.…”

Severe asthma remaining well‐controlled after mepolizumab discontinuation: A case report and literature review

“… 8 , 9 The characteristics of patients successfully discontinuing mepolizumab have been shown to have fewer asthma symptoms, well‐controlled asthma comorbidities and suppressed type 2 inflammation, such as lower blood eosinophil counts and/or FeNO levels, during the treatment of mepolizumab. 10 Further, Hamada K et al present two cases of severe eosinophilic asthma withdrawing the treatment of benralizumab, anti‐IL‐5R antibody. Asthma in one case sustained well‐controlled, while asthma in the other was deteriorated in 6 months.…”