Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort
Clairelyne Dupin
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
Search for more papers by this authorDrifa Belhadi
Groupe Hospitalier Universitaire AP-HP Nord-Université de Paris, Hôpital Bichat, Département d’Epidémiologie, Biostatistiques et Recherche Clinique Unité de Recherche Clinique, Paris, France
Clinical Investigation Center CIC-EC 1425, Inserm, Paris, France
Search for more papers by this authorLaurent Guilleminault
Pôle des Voies Respiratoires, Hôpital Larrey, CHU de Toulouse, Toulouse, France
Centre de Physiopathologie Toulouse Purpan, INSERM U1043, CNRS UMR 5282, Université Toulouse III, Toulouse, France
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Search for more papers by this authorAnne-Sophie Gamez
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France
Search for more papers by this authorPatrick Berger
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Service de Pneumologie, Inserm CIC1401, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France
Search for more papers by this authorFrédéric De Blay
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Département de Pathologie Thoracique, CHU de Strasbourg, Université de Strabsourg, Strasbourg, France
Search for more papers by this authorPhilippe Bonniaud
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Service de Pneumologie et Soins Intensifs Respiratoires, Centre Hospitalo-Universitaire de Dijon-Bourgogne, Dijon, France
Faculté de Médecine et Pharmacie, Université de Bourgogne-Franche Comté, Dijon, France
INSERM U1213, Dijon, France
Search for more papers by this authorChristophe Leroyer
Département de Médecine Interne et Pneumologie, Hôpital La Cavale Blanche, Brest, France
EA3878, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université Européenne de Bretagne, Brest, France
Search for more papers by this authorGuillaume Mahay
Service de Pneumologie, Oncologie Thoracique et Soins Intensifs Respiratoires, CHU de Rouen, Rouen, France
Search for more papers by this authorPierre-Olivier Girodet
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Service de Pneumologie, Inserm CIC1401, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France
Search for more papers by this authorChantal Raherison
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Service de Pneumologie, Inserm CIC1401, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France
Search for more papers by this authorStéphanie Fry
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
CHU Lille, Service de Pneumologie et Immuno-allergologie, Institut Pasteur Lille, Univ Lille, Lille, France
Search for more papers by this authorGeneviève Le Bourdellès
Service de Pneumologie, Hôpital Foch, Suresnes, France
Search for more papers by this authorAlain Proust
Service de Pneumologie, CH de Nîmes, Nîmes, France
Search for more papers by this authorLise Rosencher
Hôpital Tenon, AP-HP, Département de Pneumologie et Réanimation Respiratoire, Unité Fonctionnelle D’oncologie Thoracique, Paris, France
Search for more papers by this authorGilles Garcia
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Université Paris-Sud and Université Paris-Saclay, Le Kremlin-Bicêtre, France
Service de Pneumologie, AP- HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
Search for more papers by this authorArnaud Bourdin
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France
Search for more papers by this authorCécile Chenivesse
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
CHU Lille, Service de Pneumologie et Immuno-allergologie, Institut Pasteur Lille, Univ Lille, Lille, France
Search for more papers by this authorAlain Didier
Pôle des Voies Respiratoires, Hôpital Larrey, CHU de Toulouse, Toulouse, France
Centre de Physiopathologie Toulouse Purpan, INSERM U1043, CNRS UMR 5282, Université Toulouse III, Toulouse, France
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Search for more papers by this authorCamille Couffignal
Groupe Hospitalier Universitaire AP-HP Nord-Université de Paris, Hôpital Bichat, Département d’Epidémiologie, Biostatistiques et Recherche Clinique Unité de Recherche Clinique, Paris, France
Clinical Investigation Center CIC-EC 1425, Inserm, Paris, France
Search for more papers by this authorCorresponding Author
Camille Taillé
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
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Correspondence
Camille Taillé, Service de Pneumologie, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Email: [email protected]
Search for more papers by this authorClairelyne Dupin
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
Search for more papers by this authorDrifa Belhadi
Groupe Hospitalier Universitaire AP-HP Nord-Université de Paris, Hôpital Bichat, Département d’Epidémiologie, Biostatistiques et Recherche Clinique Unité de Recherche Clinique, Paris, France
Clinical Investigation Center CIC-EC 1425, Inserm, Paris, France
Search for more papers by this authorLaurent Guilleminault
Pôle des Voies Respiratoires, Hôpital Larrey, CHU de Toulouse, Toulouse, France
Centre de Physiopathologie Toulouse Purpan, INSERM U1043, CNRS UMR 5282, Université Toulouse III, Toulouse, France
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Search for more papers by this authorAnne-Sophie Gamez
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France
Search for more papers by this authorPatrick Berger
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Service de Pneumologie, Inserm CIC1401, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France
Search for more papers by this authorFrédéric De Blay
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Département de Pathologie Thoracique, CHU de Strasbourg, Université de Strabsourg, Strasbourg, France
Search for more papers by this authorPhilippe Bonniaud
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Service de Pneumologie et Soins Intensifs Respiratoires, Centre Hospitalo-Universitaire de Dijon-Bourgogne, Dijon, France
Faculté de Médecine et Pharmacie, Université de Bourgogne-Franche Comté, Dijon, France
INSERM U1213, Dijon, France
Search for more papers by this authorChristophe Leroyer
Département de Médecine Interne et Pneumologie, Hôpital La Cavale Blanche, Brest, France
EA3878, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université Européenne de Bretagne, Brest, France
Search for more papers by this authorGuillaume Mahay
Service de Pneumologie, Oncologie Thoracique et Soins Intensifs Respiratoires, CHU de Rouen, Rouen, France
Search for more papers by this authorPierre-Olivier Girodet
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Service de Pneumologie, Inserm CIC1401, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France
Search for more papers by this authorChantal Raherison
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Service de Pneumologie, Inserm CIC1401, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France
Search for more papers by this authorStéphanie Fry
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
CHU Lille, Service de Pneumologie et Immuno-allergologie, Institut Pasteur Lille, Univ Lille, Lille, France
Search for more papers by this authorGeneviève Le Bourdellès
Service de Pneumologie, Hôpital Foch, Suresnes, France
Search for more papers by this authorAlain Proust
Service de Pneumologie, CH de Nîmes, Nîmes, France
Search for more papers by this authorLise Rosencher
Hôpital Tenon, AP-HP, Département de Pneumologie et Réanimation Respiratoire, Unité Fonctionnelle D’oncologie Thoracique, Paris, France
Search for more papers by this authorGilles Garcia
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Université Paris-Sud and Université Paris-Saclay, Le Kremlin-Bicêtre, France
Service de Pneumologie, AP- HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
Search for more papers by this authorArnaud Bourdin
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France
Search for more papers by this authorCécile Chenivesse
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
CHU Lille, Service de Pneumologie et Immuno-allergologie, Institut Pasteur Lille, Univ Lille, Lille, France
Search for more papers by this authorAlain Didier
Pôle des Voies Respiratoires, Hôpital Larrey, CHU de Toulouse, Toulouse, France
Centre de Physiopathologie Toulouse Purpan, INSERM U1043, CNRS UMR 5282, Université Toulouse III, Toulouse, France
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Search for more papers by this authorCamille Couffignal
Groupe Hospitalier Universitaire AP-HP Nord-Université de Paris, Hôpital Bichat, Département d’Epidémiologie, Biostatistiques et Recherche Clinique Unité de Recherche Clinique, Paris, France
Clinical Investigation Center CIC-EC 1425, Inserm, Paris, France
Search for more papers by this authorCorresponding Author
Camille Taillé
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
INSERM, F-CRIN, Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS), Toulouse, France
Correspondence
Camille Taillé, Service de Pneumologie, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Email: [email protected]
Search for more papers by this authorAbstract
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.
Supporting Information
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