Severe asthma accounts for a disproportionate burden of morbidity, mortality and healthcare utilization among Canadians with asthma. Advances in the understanding of asthma endotypes, increasing recognition of corticosteroid-associated harms and the rapid expansion of targeted therapies have altered the therapeutic landscape. We aimed to develop a guideline to provide updated, evidence-based recommendations for the pharmacologic management of severe asthma in children (6-11 years), adolescents (12-17 years) and adults (≥18 years), with an emphasis on individualized, biomarker-informed care. The guideline was developed in accordance with the Canadian Thoracic Society (CTS) guideline development process using GRADE methodology and guided by the AGREE II framework. A comprehensive systematic review of randomized controlled trials was conducted through February 2025. Critical outcomes included exacerbations, asthma control, health-related quality of life, lung function, corticosteroid exposure, and safety. Meta-analyses were performed where appropriate, and recommendations balance benefits and harms, certainty of evidence, patient values, feasibility and cost-effectiveness in the Canadian context. This guideline introduces updates to the 2017 CTS Severe Asthma Position Statement. In adults, the focus has shifted to severe exacerbating asthma to align with contemporary trial populations and regulatory indications. New and updated recommendations address biologic therapies targeting IgE, IL-5/IL-5R, IL-4/IL-13 and thymic stromal lymphopoietin pathways, as well as long-acting muscarinic antagonists (beyond tiotropium), including single-inhaler versus multiple-inhaler triple therapy. In children and adolescents, recommendations encompass both severe controlled and severe exacerbating asthma. Some recommendations extend beyond Health Canada indications to improve equitable access to effective therapies in Canada.
