Clairelyne Dupin1, Drifa Belhadi2,3, Laurent Guilleminault4,5,6, Anne-Sophie Gamez6,7, Patrick Berger6,8, Frédéric De Blay6,9, Philippe Bonniaud6,10,11,12, Christophe Leroyer13,14, Guillaume Mahay15, Pierre-Olivier Girodet6,8, Chantal Raherison6,8, Stéphanie Fry6,16, Geneviève Le Bourdellès17, Alain Proust18, Lise Rosencher19, Gilles Garcia6,20,21, Arnaud Bourdin6,7, Cécile Chenivesse6,16, Alain Didier4,5,6, Camille Couffignal2,3, Camille Taillé1,6. 1. Groupe Hospitalier Universitaire AP-HP Nord-Université de Paris, Hôpital Bichat, Service de Pneumologie et Centre de Référence constitutif des Maladies Pulmonaires Rares, Inserm UMR 1152, Paris, France. 2. Groupe Hospitalier Universitaire AP-HP Nord-Université de Paris, Hôpital Bichat, Département d'Epidémiologie, Biostatistiques et Recherche Clinique Unité de Recherche Clinique, Paris, France. 3. Clinical Investigation Center CIC-EC 1425, Inserm, Paris, France. 4. Pôle des Voies Respiratoires, Hôpital Larrey, CHU de Toulouse, Toulouse, France. 5. Centre de Physiopathologie Toulouse Purpan, INSERM U1043, CNRS UMR 5282, Université Toulouse III, Toulouse, France. 6. INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France. 7. Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France. 8. Service de Pneumologie, Inserm CIC1401, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France. 9. Département de Pathologie Thoracique, CHU de Strasbourg, Université de Strabsourg, Strasbourg, France. 10. Service de Pneumologie et Soins Intensifs Respiratoires, Centre Hospitalo-Universitaire de Dijon-Bourgogne, Dijon, France. 11. Faculté de Médecine et Pharmacie, Université de Bourgogne-Franche Comté, Dijon, France. 12. INSERM U1213, Dijon, France. 13. Département de Médecine Interne et Pneumologie, Hôpital La Cavale Blanche, Brest, France. 14. EA3878, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université Européenne de Bretagne, Brest, France. 15. Service de Pneumologie, Oncologie Thoracique et Soins Intensifs Respiratoires, CHU de Rouen, Rouen, France. 16. CHU Lille, Service de Pneumologie et Immuno-allergologie, Institut Pasteur Lille, Univ Lille, Lille, France. 17. Service de Pneumologie, Hôpital Foch, Suresnes, France. 18. Service de Pneumologie, CH de Nîmes, Nîmes, France. 19. Hôpital Tenon, AP-HP, Département de Pneumologie et Réanimation Respiratoire, Unité Fonctionnelle D'oncologie Thoracique, Paris, France. 20. Université Paris-Sud and Université Paris-Saclay, Le Kremlin-Bicêtre, France. 21. Service de Pneumologie, AP- HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
Abstract
BACKGROUND: Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations. OBJECTIVE: To assess changes in asthma control between baseline and 12 months of treatment. METHODS: Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447). RESULTS: Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators. CONCLUSION & CLINICAL RELEVANCE: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia.
BACKGROUND:Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations. OBJECTIVE: To assess changes in asthma control between baseline and 12 months of treatment. METHODS: Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447). RESULTS: Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators. CONCLUSION & CLINICAL RELEVANCE: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia.
Authors: Eustachio Nettis; Luisa Brussino; Vincenzo Patella; Laura Bonzano; Aikaterini Detoraki; Elisabetta Di Leo; Maria Maddalena Sirufo; Cristiano Caruso; Fabio Lodi Rizzini; Mariaelisabetta Conte; Mona-Rita Yacoub; Massimo Triggiani; Erminia Ridolo; Luigi Macchia; Giovanni Rolla; Raffaele Brancaccio; Amato De Paulis; Giuseppe Spadaro; Danilo Di Bona; Angela Maria D'Uggento; Lia Ginaldi; Francesco Gaeta; Eleonora Nucera; Kliljeda Jaubashi; Danilo Villalta; Lorenzo Dagna; Domenico Ciotta; Francesco Pucciarini; Diego Bagnasco; Giorgio Celi; Fulvia Chieco Bianchi; Lorenzo Cosmi; Maria Teresa Costantino; Maria Angiola Crivellaro; Simona D'Alò; Pietro Del Biondo; Stefano Del Giacco; Mario Di Gioacchino; Linda Di Pietro; Elisabetta Favero; Sebastiano Gangemi; Gabriella Guarnieri; Enrico Heffler; Maria Stefania Leto Barone; Carla Lombardo; Francesca Losa; Andrea Matucci; Paola Lucia Minciullo; Paola Parronchi; Giovanni Passalacqua; Stefano Pucci; Oliviero Rossi; Lorenzo Salvati; Michele Schiappoli; Gianenrico Senna; Andrea Vianello; Alessandra Vultaggio; Yang Baoran; Cristoforo Incorvaia; Giorgio Walter Canonica Journal: Clin Mol Allergy Date: 2022-05-19
Authors: Regina Maria de Carvalho-Pinto; José Eduardo Delfini Cançado; Marcia Margaret Menezes Pizzichini; Jussara Fiterman; Adalberto Sperb Rubin; Alcindo Cerci Neto; Álvaro Augusto Cruz; Ana Luisa Godoy Fernandes; Ana Maria Silva Araujo; Daniela Cavalet Blanco; Gediel Cordeiro Junior; Lilian Serrasqueiro Ballini Caetano; Marcelo Fouad Rabahi; Marcelo Bezerra de Menezes; Maria Alenita de Oliveira; Marina Andrade Lima; Paulo Márcio Pitrez Journal: J Bras Pneumol Date: 2021-12-15 Impact factor: 2.624