Anti-IL-4R versus anti-IL-5/5R after anti-IL-5/5R failure in asthma: An emulated target trial
- PMID: 38848878
- DOI: 10.1016/j.jaci.2024.05.023
Anti-IL-4R versus anti-IL-5/5R after anti-IL-5/5R failure in asthma: An emulated target trial
Abstract
Background: Switching biologics is now common practice in severe eosinophilic asthma. After insufficient response to anti-IL-5 or 5 receptor (anti-IL-5/5R), the optimal switch between an anti-IL-4R mAb (interclass) or another anti-IL-5/5R drug (intraclass) remains unknown.
Objective: We sought to compare the effectiveness of these 2 strategies in asthma control in patients with severe eosinophilic asthma and insufficient response to an anti-IL-5/5R mAb.
Methods: We emulated a target randomized trial using observational data from the Recherche sur les AsthMes SEvèreS (RAMSES) cohort. Eligible patients were switched to an anti-IL-4R mAb or another anti-IL-5/5R drug after insufficient response to an anti-IL-5/5R mAb. The primary outcome was the change in Asthma Control Test score at 6 months.
Results: Among the 2046 patients in the cohort, 151 were included in the study: 103 switched to an anti-IL-4R mAb and 48 to another anti-IL-5/5R. At 6 months, the difference in Asthma Control Test score improvement was not statistically significant (mean difference groups, 0.82 [-0.47 to 2.10], P = .213). The interclass group exhibited greater cumulative reduction in oral corticosteroid dose (Pinter-intra, -1.05 g [-1.76 to -0.34], P = .041). The interclass group had a better effect, although not significantly, on reducing exacerbations (Δinter-intra, -0.37 [-0.77 to 0.02], P = .124) and increasing lung function (FEV1) (126.8 mL [-12.7 to 266.4], P = .124).
Conclusions: After anti-IL-5/5R mAb insufficient response, switching to dupilumab demonstrated similar improvement in Asthma Control Test scores compared with intraclass switching. However, it appeared more effective in reducing oral corticosteroid use. Larger studies are warranted to confirm these results.
Keywords: Mepolizumab; benralizumab; dupilumab; severe asthma; treatment switch.
Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosure statement The RAMSES cohort is funded by the French Pneumology Society (SPLF, Société de Pneumologie de Langue Française), AstraZeneca, GlaxoSmithKline, Sanofi as well as Boston Scientific and Novartis. The funders were not involved in the study initiative, statistical analysis plan, interpretation of results, and decision to publish the current study. The Délégation à la Recherche Clinique et à l’Innovation de l'Assistance Publique-Hôpitaux de Paris is the sponsor of the RAMSES cohort. S.V. was awarded a research grant “Année Recherche” by the Regional Health Agency (Agence Régionale de Santé, Ile-de-France). Disclosure of potential conflict of interest: C. Taillé received fees from Sanofi, AstraZeneca, GlaxoSmithKline, and Novartis for advisory board education and has been an investigator for trials sponsored by Sanofi, AstraZeneca, GlaxoSmithKline, and Novartis, outside of this work. C. Chenivesse received grants from AstraZeneca, GlaxoSmithKline, Novartis, and Santelys, personal fees from ALK-Abelló, AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, and Sanofi-Regeneron, and congress support from AstraZeneca, Boehringer-Ingelheim, Chiesi, Novartis, and Sanofi-Regeneron. G. Devouassoux received grants for clinical research from GlaxoSmithKline and Sanofi, consulting fees from Sanofi, AstraZeneca, GlaxoSmithKline, Chiesi, Menarini, and ALK, payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Sanofi, AstraZeneca, GlaxoSmithKline, Chiesi, Menarini, and ALK, and for expert testimony and attending meetings and/for travel from Sanofi, AstraZeneca, and GlaxoSmithKline. P. Bonniaud received research grants from AstraZeneca, payment or honoraria for symposium from Sanofi and AstraZeneca, support for attending medical and research meetings from AstraZeneca, Novartis, Sanofi, Boehringer, and Stallergene, and personal fees for advisory board from AstraZeneca, Novartis, Sanofi, GlaxoSmithKline, and Boehringer. A. Beurnier received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AstraZeneca and Sanofi. A. Bourdin received grants or contracts from AstraZeneca, Boeringher, and GlaxoSmithKline, consulting fees from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi, Celtrion, Boeringher, and Novartis, payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AstraZeneca, Sanofi-Regeneron, GlaxoSmithKline, Boeringher, and Novartis, support for attending meetings and/or travel from AstraZeneca and Sanofi, and participation on a Data Safety Monitoring Board or Advisory Board from ABscience. A. Boudjemaa received consulting fees from AstraZeneca, payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AstraZeneca, Sanofi Genzyme, GlaxoSmithKline, support for attending meetings and/or travel from AstraZeneca, Sanofi Genzyme, and GlaxoSmithKline, and participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Sanofi Genzyme, GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest.
