Abstract: Severe eosinophilic asthma represents a relatively small proportion of the overall asthma population but accounts for a disproportionate burden of exacerbations, oral corticosteroid (OCS) exposure and healthcare use. The advent of biologic therapies targeting type 2 (T2) inflammation has made clinical remission a realistic goal and raised new questions about how and when to de-escalate inhaled corticosteroids (ICS) and biologics in patients achieving stable disease. This narrative review summarizes current evidence and expert recommendations on: definitions and levels of clinical remission in severe eosinophilic asthma; the role of different biologics in inducing remission; safety and feasibility of ICS and biologic de-escalation after remission; and clinical and biological predictors of sustained remission and successful step-down. Biologics such as anti-IgE, anti-IL-5/5Rα, anti-IL-4Rα and anti-thymic stromal lymphopoietin (TSLP) markedly reduce exacerbations, OCS use and, in a substantial minority of patients, induce clinical or “deep” remission on-treatment. Prospective randomized controlled trials and real-world data (e.g. SHAMAL and registry studies) indicate that structured, physician-guided ICS reduction is feasible for many patients without loss of control, whereas abrupt or unsupervised reduction is associated with worse outcomes. Evidence on biologic withdrawal is more heterogeneous: discontinuation of mepolizumab, tezepelumab or omalizumab frequently leads to loss of control, although a subset maintains remission off-treatment. Favorable predictors of remission and tolerability of de-escalation include fewer prior exacerbations, lower chronic OCS exposure, shorter disease duration, better preserved FEV 1 and effective suppression of T2 biomarkers. Within the context of severe eosinophilic asthma remission, de-escalation of therapy may follow a cautious, hierarchical, clinician-led strategy prioritizing OCS, then ICS, and only subsequently biologics, with predefined failure criteria and shared decision-making. This proposed pathway is presented as a pragmatic synthesis of the available evidence and should be interpreted as expert opinion rather than formal guideline recommendations. Robust, standardized definitions and validated predictors are still needed to safely expand off-treatment remission to a larger proportion of patients. Keywords: severe asthma, clinical remission, predictive factors, biologic therapies, de-escalation
Lupia et al. (Sun,) studied this question.