Emerging therapeutic strategies and clinical trials in severe asthma management: current evidence and future directions

Abstract

Introduction Biologic therapies have transformed the management of severe asthma, particularly in type 2-high disease, but important unmet needs remain. Incomplete responses, uncertainty in treatment positioning, and the lack of effective options for non-type 2 or mixed inflammatory endotypes continue to limit the achievement of deeper and more durable disease control.Areas covered This review examines the evolving therapeutic landscape of severe asthma, moving from currently approved biologics to emerging strategies directed at upstream mediators and novel pathways, including alarmins, tumor necrosis factor-like cytokine 1A (TL1A)-related signaling, multi-target biologics, and next-generation anti-immunoglobulin E (IgE) approaches. It also discusses how recent clinical trials have expanded traditional efficacy outcomes by incorporating inhaled corticosteroid reduction, biomarker modulation, small airway dysfunction, mucus plugging, treatment burden, remission, and possible disease modification.Expert opinion The field is moving beyond exacerbation reduction toward deeper and more durable disease control. Future progress will depend on improved biological stratification, more informative biomarkers, comparative effectiveness data, and therapeutic strategies capable of extending benefit beyond conventional type 2-high disease. In parallel, greater emphasis on remission-oriented and potentially disease-modifying care is likely to reshape both trial design and clinical practice in severe asthma.