Predictive Factors And Treatments Associated with Clinical Remission in Severe Eosinophilic Asthma

Chiara Lupia,1 Guido Marchi,2 Emanuela Chiarella,3 Giovanna Lucia Piazzetta,3 Nadia Lobello,3 Claudia Crimi,4 Remo Poto,5 Angelantonio Maglio,6 Alessandro Vatrella,6 Girolamo Pelaia,1 Corrado Pelaia3 1Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy; 2Pulmonology Unit, Cardiothoracic and Vascular Department, University Hospital of Pisa, Pisa, Italy; 3Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy; 4Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; 5Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; 6Department of Medicine, Surgery, and Dentistry, University of Salerno, Salerno, ItalyCorrespondence: Corrado Pelaia, University “Magna Graecia” of Catanzaro, Department of Medical and Surgical Sciences, Viale Europa – Località Germaneto, Catanzaro, 88100, Italy, Tel + 39 0961 3647007, Fax + 39 0961 3647193, Email pelaia.corrado@unicz.itAbstract: 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 FEV1 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