Benralizumab for eosinophilic granulomatosis with polyangiitis.


Journal

Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355

Informations de publication

Date de publication:
12 2023
Historique:
received: 27 06 2023
accepted: 25 07 2023
medline: 13 11 2023
pubmed: 8 8 2023
entrez: 7 8 2023
Statut: ppublish

Résumé

Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series. We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day. Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004). Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab.

Sections du résumé

BACKGROUND
Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series.
METHODS
We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day.
RESULTS
Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004).
CONCLUSIONS
Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab.

Identifiants

pubmed: 37550002
pii: ard-2023-224624
doi: 10.1136/ard-2023-224624
doi:

Substances chimiques

benralizumab 71492GE1FX
Prednisone VB0R961HZT
Glucocorticoids 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1580-1586

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: The authors declare no financial support. MG reports personal fees from GlaxoSmithKline and AstraZeneca outside the submitted work. CT reports personal fees from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi and Novartis outside the submitted work. CDupin reports personal fees from AstraZeneca and GlaxoSmithKline outside the submitted work. HY reports personal fees from GlaxoSmithKline outside the submitted work. Other authors has nothing to disclose.

Auteurs

Adrien Cottu (A)

Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, Paris, France.

Matthieu Groh (M)

National Referral Center for Hypereosinophilic Syndrome (CEREO), Department of Internal Medicine, Hopital Foch, Suresnes, France.

Charlene Desaintjean (C)

Department of Respiratory Diseases, Hospital for Cardiologie and Pneumology Louis Pradel, Lyon, France.

Sylvain Marchand-Adam (S)

Service de pneumologie et d'explorations fonctionnelles respiratoires, CHRU de Tours, Tours, France.

Loïc Guillevin (L)

Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, Paris, France.

Xavier Puechal (X)

Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, Paris, France.

Stacy Beaumesnil (S)

Department of Internal Medicine and Infectious Diseases, University Hospital Centre, Bordeaux, France.

Estibaliz Lazaro (E)

Department of Internal Medicine and Infectious Diseases, University Hospital Centre, Bordeaux, France.

Maxime Samson (M)

Department of Internal Medicine and Clinical Immunology, University Hospital Centre, Dijon, France.

Camille Taille (C)

Reference Center for Rare Pulmonary Diseases and University of Paris Cité, Inserm 1152, Hospital Bichat - Claude-Bernard, Paris, France.

Cécile-Audrey Durel (CA)

Department of Internal Medicine, Edouard Herriot Hospital, Lyon, France.

Elizabeth Diot (E)

Department of Internal Medicine, CHRU de Tours, Tours, France.

Sarah Nicolas (S)

Department of Internal Medicine, CHRU de Tours, Tours, France.

Laurent Guilleminault (L)

Department of Respiratory Medicine, University Hospital Centre Toulouse, Toulouse, France.
Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Inserm U1291, CNRS U5282, Toulouse 2 University, Toulouse, France.

Mikael Ebbo (M)

Departement of Internal Medicine, Assistance Publique - Hôpitaux de Marseille, Marseille, France.

Pascal Cathebras (P)

Department of Internal Medicine, CHU, Saint-Etienne, France.

Clairelyne Dupin (C)

Reference Center for Rare Pulmonary Diseases and University of Paris Cité, Hospital Bichat - Claude-Bernard, Paris, France.

Halil Yildiz (H)

Department of Internal Medicine and Infectious Diseases, Cliniques universitaires Saint-Luc, Bruxelles, Belgium.

Nabil Belfeki (N)

Department of Internal Medicine and Clinical Immunology, Groupe Hospitalier Sud Ile-de-France, Melun, France.

Grégory Pugnet (G)

Department of Internal Medicine and Clinical Immunology, CHU Toulouse Rangueil, Toulouse, France.

Pierre Chauvin (P)

Department of Respiratory Diseases, University Hospital Centre Rennes, Rennes, France.

Stephane Jouneau (S)

Department of Respiratory Diseases, IRSET UMR 1085, Rennes 1 University, Pontchaillou Hospital, Rennes, France.

Francois Lifermann (F)

Department of Internal Medicine, Centre Hospitalier de Dax, Dax, France.

Jean-Philippe Martellosio (JP)

Department of Internal Medicine, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.

Vincent Cottin (V)

Department of Respiratory Diseases, Hospital for Cardiologie and Pneumology Louis Pradel, Lyon, France.

Benjamin Terrier (B)

Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, Paris, France benjamin.terrier@aphp.fr.
Université Paris Cité, Paris, France.

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