Feasibility of a 50% Dosing Interval Extension of Anti–IL-5 Biologics in Patients with Severe Asthma in Clinical Remission: A Real-World Validation Study

Mirna Vergles,1 Grgur Salai,1 Neven Tudorić,2 Ivona Kovačević,1 Domagoj Kifer,3 Kristina Lalić,1 Marija Gomerčić Palčić,4 Andrea Vukić Dugac5 1Department of Pulmonology, University Hospital Dubrava, Zagreb, Croatia; 2Pulmonary Outpatient Clinic, St. Catherine Specialty Hospital, Zagreb, Croatia; 3Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia; 4Department of Pulmonology, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia; 5Clinic for Respiratory Diseases, University Hospital Centre Zagreb, Zagreb, CroatiaCorrespondence: Mirna Vergles, Department of Pulmonology, University Hospital Dubrava, Zagreb, Croatia, Email [email protected]: Initiation criteria for biologic therapies for severe asthma are well established, but guidance on dose reduction or discontinuation remains limited. Sustained clinical remission presents an opportunity to evaluate biologic dose tapering strategies.Objective: To validate a down-titration algorithm by assessing the feasibility and safety of extending the dosing interval of anti–IL-5 biologics (mepolizumab, benralizumab) by 50% in patients with severe asthma in clinical remission.Methods: In this single-center, real-world, longitudinal study, 31 patients with severe asthma and sustained four-component remission for > 12 months were enrolled. The biologic dosing interval was extended by 25% at baseline and by 50% at 6 months if four-component remission was maintained. Remission was assessed at 26 and 52 weeks using established three- and four-component criteria. Bayesian logistic and mixed-effects models were used to evaluate clinical and biomarker outcomes.Results: Over the 12-month study period, a 50% dose interval extension was successfully achieved in 28 out of 31 patients (90%). At study end, 18 patients (58%) remained in four-component remission, while 25 (81%) met three-component remission criteria. Acute exacerbations occurred in 3 patients (10%). Comparison between benralizumab and mepolizumab showed no significant differences. While peripheral eosinophil counts increased slightly, mean levels remained below 300 cells/μL. FeNO levels showed no significant change.Conclusion: Following a 50% extension of anti–IL-5 biologic dosing intervals, full four-component clinical remission was maintained in 58% of patients, while 81% preserved three-component remission with a low exacerbation rate. These findings indicate that a uniform 50% interval extension cannot be applied universally without risk of partial loss of disease control. However, the high proportion of patients maintaining clinically meaningful 3-component remission supports the feasibility of a structured, stepwise dosing-interval extension strategy in selected patients with severe asthma, emphasizing the need for individualized implementation.Keywords: asthma, severe asthma, biological therapy, anti-IL-5 therapy, biological therapy titration