Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort

Clairelyne Dupin¹, Drifa Belhadi^{2

3}, Laurent Guilleminault^{4

5

6}, Anne-Sophie Gamez^{6

7}, Patrick Berger^{6

8}, Frédéric De Blay^{6

9}, Philippe Bonniaud^{6

10

11

12}, Christophe Leroyer^{13

14}, Guillaume Mahay¹⁵, Pierre-Olivier Girodet^{6

8}, Chantal Raherison^{6

8}, Stéphanie Fry^{6

16}, Geneviève Le Bourdellès¹⁷, Alain Proust¹⁸, Lise Rosencher¹⁹, Gilles Garcia^{6

20

21}, Arnaud Bourdin^{6

7}, Cécile Chenivesse^{6

16}, Alain Didier^{4

5

6}, Camille Couffignal^{2

3}, Camille Taillé^{1

6}

Affiliations

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.

PMID: 32469092
DOI: 10.1111/cea.13614

Clinical Trial

Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort

Clairelyne Dupin et al. Clin Exp Allergy. 2020 Jul.

. 2020 Jul;50(7):789-798.

doi: 10.1111/cea.13614. Epub 2020 May 29.

Authors

Affiliations

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.

PMID: 32469092
DOI: 10.1111/cea.13614

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.

Keywords: T2 inflammation; asthma; hypereosinophilia; oral steroid; side-effect.

PubMed Disclaimer

References

REFERENCES

1. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43(2):343-373
1. Bourdin A, Fabry-Vendrand C, Ostinelli J, et al. The burden of severe asthma in France: A case-control study using a medical claims database. J Allergy Clin Immunol Pract. 2019;7(5):1477-1487
1. Hekking P-PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135(4):896-902
1. Nordon C, Grimaldi-Bensouda L, Pribil C, et al. Clinical and economic burden of severe asthma: A French cohort study. Respir Med. 2018;144:42-49
1. Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455-2466

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

Associated data

Actions
- Search in PubMed
- Search in ClinicalTrials.gov

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Wiley
Medical

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort

Affiliations

Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical