Anti–IL-4R versus anti–IL-5/5R after anti–IL-5/5R failure in asthma: An emulated target trial - 13/07/24

Doi : 10.1016/j.jaci.2024.05.023

Solène Valery, MD, MPH ^a,^b,^c,^d, Noémie Simon-Tillaux, MD, MPH ^e, Gilles Devouassoux, MD, PhD ^c,^f, Philippe Bonniaud, MD, PhD ^c,^g,^h, Antoine Beurnier, MD, MSc ^c,ⁱ, Amel Boudjemaa, MD ^j, Cécile Chenivesse, MD, PhD ^c,^k, Arnaud Bourdin, MD, PhD ^c,^l,^m, Lisa Gauquelin, MSc ^d, Sylvie Guillo, MSc ^d, Camille Taillé, MD, PhD ^a,^b,^c, Candice Estellat, MD, PhD ^d,^⁎
and the
RAMSES Study Group^∗
Study Group members are listed in the Acknowledgments.
G. Devouassoux, C. Taillé, P. Chanez, P. Bonniaud, A. Bourdin, C. Saint Raymond, C. Maurer, A. Beurnier, P. Roux, V. Margelidon, A. Boudjemaa, G. Mangiapan, N. Freymond, T. Didi, M. Russier, G. Garcia, E. Popin Meyer, C. Dupin, F. Fouquet, S. Jouveshomme, W. Gaspard, S. Dury, S. Habib Maillard, A. Izadifar, E. Cuvillon, G. Deslée, C. Barnig, J.M. Perotin, A.S. Gamez, J.P. Oster, N. Khayat, C. Chenivesse, X. Li, C. Appere de Vecchi, A. Gicquello, H. Rami, G. Vignal, N. Just, X. Blanc, C. Leroyer, L. Wemeau, A. Achkar, C. Sattler, E. Catherinot, L. Guilleminault, M. Gaillot-Drevon, C. Rochefort-Morel, F. Couturaud, P. Martin, A. Chabrol, H. Pegliasco, L. Sése, S. Romanet, B. Caverstri, C. Tcherakian, A. Magnan, E. Ahmed, F. Allibe, G. Beltramo, K. Michaux, N. Paleiron, S. Martinez, C. Begne, C. Tummino, C. Givel, G. Mourin, H. Salvator, M. Volpato, M. Drucbert, N. Rossignoli, S. Keddache, A. Justet, C. Andrejak, J. Valcke, J. Perrin, M. Mercy, M. Jouvenot, T. Soumagne, X. Elharrar, B. Douvry, B. Godbert, B. Maitre, C. Goyard, A. Didier, E. Cadet, F. Chabot, J. Gonzalez, L. Mattei, M. Gouitaa, S. Chauveau, S. Raymond, S. Dirou, S. Fry, A. Briault, A. Moui, A. Paris, E. NoelSavina, C. Olivier, E. Caradec, N. Roche, G. Picart, L. Belmont, L. Portel, M. Rocca Serra, N. Guibert, R. Jean, S. Hadjadj, S. Guillo, L. Gauquelin, C. Estellat, A. Prigent, M. Larrousse, D. Jaffuel, Karima Bourayou, Eve Klising, Nessima Yelles, Sarra Pochon, Amal Gouider, Hadj Kaci Medina, Sellali Yasmine, Dahmani Djouher, Diakhou Ndao, Yannick Vacher, Antoine Achkar, Engi Ahmed, Didier Alain, Flora Allibe, Claire Andrejak, Corinne Appere De Vecchi, Cindy Barnig, Camille Begne, Laure Belmont, Guillaume Beltramo, Xavier Blanc, Amandine Briault, Emmanuelle Cadet, Emmanuela Caradec, Émilie Catherinot, Beatrice Cavestri, Alexandre Chabrol, Pascal Chanez, Simon Chauveau, Francis Couturaud, Édouard Cuvillon, Gaëtan Deslee, Toufik Didi, Stéphanie Dirou, benoît Douvry, Mélanie Drucbert, Clairelyne Dupin, Sandra Dury, Xavier Elharrar, Helen Fouquet, Nathalie Freymond, Stéphanie Fry, Maud Gaillot-Drevon, Anne Sophie Gamez, Gilles Garcia, Wanda Gaspard, Alice Gicquello, Claire Givel, benoit Godbert, Jésus Gonzalez, Marion Gouitaa, François Goupil, Céline Goyard, Nicolas Guibert, Laurent Guilleminault, Stéphanie Habib-Maillard, Samra Hadjadj, Armine Izadifar, Romain Jean, marie Jouvenot, Stéphane Jouveshomme, Nicolas Just, Aurélien Justet, Sophia Keddache, Naji Khayath, Bertrand Lemaire, Christophe Leroyer, Xing Li, Antoine Magnan, Bernard Maitre, Gilles Mangiapan, Victor Margelidon, Pascale Martin, Stéphanie Martinez, Laura Mattei, Cyril Maurer, Magalie Mercy, Karine Michaux, Antoine Moui, Gisèle Mourin, Elisa Noel-Savina, Cécile Olivier, Jean-Philippe Oster, Nicolas Paleiron, Audrey Paris, Hervé Pegliasco, Jeanne-Marie Perotin Collard, Julie Perrin, Gaël Picart, Christophe Pison, Élisabeth Popin-Meyer, Laurent Portel, Hassina Rami, Stéphane Raymond, Mireille Rocca Serra, Cécile Rochefort-Morel, Stéphanie Romanet, Nadine Rossignoli, Pauline Roux, Maud Russier, Christel Saint-Raymond, Sergio Salmeron, Helene Salvator, Caroline Sattler, Lucile Sese, Thibaud Soumagne, Colas Tcherakian, Angélica Tiotiu, Céline Tummino, Judith Valcke-Brossollet, Guillaume Vignal, Mathilde Volpato, Lidwine Wemeau

^a Service de Pneumologie et Centre de référence pour les maladies respiratoires rares, Hôpital Bichat, AP-HP Nord-Université Paris Cité, Paris, France
^b UMR 1152, Paris, France
^c CRISALIS F-CRIN Network, Toulouse, France
^d Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, équipe PEPITES, AP-HP, Hôpital Pitié-Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Paris, France
^e Equipe 2-Oncostat U1018, Inserm, University Paris-Saclay, labeled Ligue Contre le Cancer, Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France
^f Service de Pneumologie, Hôpital de la Croix Rousse, Lyon, France
^g Service de Pneumologie et Soins Intensifs Respiratoire, Centre Hospitalier Universitaire de Bourgogne, Dijon, France
^h INSERM U1231, Equipe HSP-pathies, Faculty of Medicine and Pharmacy, University of Bourgogne-Franche Comté, Dijon, France
ⁱ Department of Respiratory and Intensive Care Medicine, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
^j Service de pneumologie, Centre Hospitalier intercommunal de Créteil, Créteil, France
^k Université de Lille, CNRS, Inserm, CHU Lille, Service de Pneumologie et Immuno-Allergologie, U1019 - UMR 9017- CIIL - Center for Infection and Immunity of Lille, Lille, France
^l Department of Respiratory Diseases, University of Montpellier, Montpellier, France
^m PhyMedExp, University of Montpellier, CNRS, INSERM CHU Montpellier, Montpellier, France

^∗Corresponding author: Candice Estellat, MD, PhD, Hôpital Pitié-Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi) 47 boulevard de l'Hôpital, 75013, Paris, France.Hôpital Pitié-Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi) 47 boulevard de l'HôpitalParis75013France

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Graphical abstract

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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 (P_inter-intra, −1.05 g [−1.76 to −0.34], P = .041). The interclass group had a better effect, although not significantly, on reducing exacerbations (Δ_inter-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.

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Key words : Mepolizumab, dupilumab, benralizumab, severe asthma, treatment switch

Abbreviations used : ACT, AQLQ, BEC, CRwNP, OCS, OR, RAMSES, SA