Choice dilemmas in the use of biologics for severe asthma management
Published online January 24, 2025
Asthma is a chronic inflammatory condition of the airways, characterized by fluctuating respiratory symptoms and hyperresponsiveness. While the majority of individuals experience mild forms of the disease, a smaller subset is affected by severe asthma, defined as uncontrolled disease despite intensive pharmacological therapy and associated with diminished quality of life and high healthcare costs. In recent years, asthma has increasingly been understood as a heterogeneous disease with distinct underlying biological mechanisms. This evolving understanding has facilitated the development of targeted biologic therapies aimed at specific immune pathways. These biologics have shown impressive clinical efficacy. Selecting the most appropriate treatment remains challenging for physicians, particularly in patients who exhibit overlapping phenotypic characteristics or qualify for multiple therapeutic options. However, this problem is underrecognized in the literature.
A study by Cote et al., recently published in The Journal of Allergy and Clinical Immunology: In Practice, emphasizes the limitations of current treatment selection strategies and investigates variations in biologic prescribing practices among asthma specialists in complex clinical scenarios. The study used a two-phase survey methodology. The initial pilot phase was conducted in Quebec, Canada, followed by an international phase through the International Severe Asthma Registry (ISAR) network, which includes clinicians from 25 countries. Eligible participants were defined as asthma specialists who regularly prescribe biologics. Respondents evaluated seven real-life vignette cases of patients with severe asthma who were prescribed a monoclonal antibody therapy for their asthma. Each vignette included detailed clinical data and biomarkers, and physicians were asked to determine whether biologic treatment was warranted and to select which biologic they thought would be best to treat the patient. They could choose initially from four options (omalizumab, mepolizumab, reslizumab and benralizumab) with a fifth (dupilumab) added in a follow-up question. Participants also provided justification for their choices. Demographic and practice-related information was collected to characterize respondents. The survey was conducted anonymously using REDCap, and statistical analyses including Gwet’s AC1 coefficient were used to evaluate inter-observer agreement and explore subgroup differences.
The study revealed considerable variability among asthma specialists in both the decision to initiate biologic treatment and in the specific choice of monoclonal antibody for severe asthma cases. Response rates were 34.8% in the pilot phase (Quebec) and 21.2% in the international phase. Responders were experienced asthma specialists’ managing a large number of severe asthma cases requiring monoclonal antibodies. Agreement to start a biologic was moderate in the pilot (Gwet’s AC1 = 0.48) and fair internationally (AC1 = 0.33), while agreement on the specific biologic choice was only fair across all phases and subgroups. The availability of Dupilumab would have influenced treatment decisions in a large proportion of cases, further decreasing interobservers’ agreement. Finally, less than half of the respondents selected the same therapy as the one ultimately used in practice. Although clinical response to other choices could not be determined, the study was designed to highlight the challenges when it comes to the choice of optimal therapy in severe asthma. The variability in response certainly supports this problem.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.
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