Benralizumab in Eosinophilic Granulomatosis with Polyangiitis

Adrien Cottu¹, Matthieu Groh², Charlène Desaintjean³, Sylvain Marchand-Adam⁴, Loic Guillevin⁵, Xavier Puéchal⁶, Estibaliz Lazaro⁷, Maxime Samson⁸, Camille Taillé⁹, Cécile-Audrey Durel¹⁰, Elisabeth Diot¹¹, Sarah Nicolas¹¹, Laurent Guilleminault¹², Mikael Ebbo¹³, Pascal Cathébras¹⁴, Clairelyne Dupin⁹, Halil Yildiz¹⁵, Nabil Belfeki¹⁶, Gregory Pugnet¹⁷, Pierre Chauvin¹⁸, Stephane Jouneau¹⁹, François Lifermann²⁰, Jean-Philippe Martellosio²¹, Vincent Cottin²² and Benjamin Terrier²³, ¹Department of Internal Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, ²National Referral Center for Hypereosinophilic Syndrome (CEREO), Hôpital Foch, Suresnes, France, ³Department of Respiratory Diseases, Hôpital Louis Pradel, Lyon, France, ⁴CHRU Tours, service de pneumologie et d'explorations fonctionnelles respiratoires, Tours, France, ⁵University Paris Descartes, Paris, France, ⁶National Referral Center for Rare Systemic Autoimmune Diseases, Paris, France, ⁷Bordeaux Hospital University, Pessac, France, ⁸Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France, ⁹AP-HP, Bichat Hospital, Reference Center for Rare Pulmonary Diseases and University of Paris Cité, Inserm 1152, Paris, France, ¹⁰CHU Lyon, Lyon, France, ¹¹Service de médecine interne et immunologie clinique, CHU Tours, Tours, France, ¹²Department of respiratory and allergic diseases, Toulouse University Hospital Center, Toulouse, France, ¹³Aix Marseille Univ, APHM, hôpital de la Timone, Internal Medicine Department, Marseille, France, ¹⁴Department of Internal medicine, Hôpital Nord, CHU St Etienne, Saint-Etienne, France, ¹⁵Saint Luc Hospital, Bruxelles, Belgium, ¹⁶Service de Médecine Interne et Immunologie Clinique. Groupe Hospitalier Sud Île de France, Melun, France, ¹⁷CHU Toulouse Rangueil Service de Medecine Interne et Immunologie Clinique, Toulouse, France, ¹⁸Department of Respiratory Diseases, Rennes University Hospital, Rennes, France, ¹⁹Amicus, Boca Raton, FL, ²⁰Department of Internal Medicine, Centre Hospitalier de Dax, Dax, France, ²¹Service de médecine interne, maladies infectieuses et tropicales, CHU de Poitiers, Poitiers, France, ²²Coordinating Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, University of Lyon, INRAE, Lyon, France, ²³Department of Internal Medicine, Hôpital Cochin, AP-HP, Paris, France

Meeting: ACR Convergence 2023

Keywords: corticosteroids, Disease-Modifying Antirheumatic Drugs (Dmards), Eosinophilic Granulomatosus with Polyangiitis (Churg-Strauss)

Session Information

Date: Sunday, November 12, 2023

Title: (0673–0690) Vasculitis – ANCA-Associated Poster I: Treatment Outcomes

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Gucocorticoid (GC)-dependant asthma and ENT exacerbations may persist in more than 80% of eosinophilic granulomatosis with polyangiitis (EGPA). The MIRRA trial demonstrated the efficacy of mepolizumab, a monoclonal antibody targeting interleukin-5 (IL-5), in treating these manifestations. However, roughly 70% of patients still required more than 4 mg per day of prednisone at the end of follow-up or relapsed. Benralizumab, a monoclonal-antibody targeting IL-5 receptor, causes profound eosinophil depletion in plasma, sputum, and tissues. However, its efficacy in GC-dependent manifestations remains to be determined in EGPA. We aimed to describe the use and efficacy of benralizumab in patients with refractory manifestations of EGPA.

Methods: We conducted a multicentre, retrospective study of patients with EGPA according to ACR/EULAR 2022 criteria and treated with benralizumab between February 2019 and February 2023. Complete response was defined as no disease activity (BVAS=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day. Total response was defined by either complete or partial response. Comparisons between patients with and without prior mepolizumab therapy were made using the Fisher exact test and the Mann Whitney test. Comparisons of responses or time to vasculitis flares were made with log-rank test.

Results: Sixty-eight patients were included. The median age was 50 (IQR 39-63) years. ANCA were positive in 20 (29%) patients at EGPA diagnosis. Thirty-one patients (46%) had previously received mepolizumab, at a dose of 100 mg/month in 18/26 (69%) and 300 mg/month in 8/26 (31%). Primary or secondary failure of mepolizumab accounted for 16 patients (52%) and 15 patients (48%). The use of benralizumab was justified by uncontrolled asthma in 54 (81%), uncontrolled ENT manifestations in 27 (40%) and persistent glucocorticoid use in 48 (74%) patients. The asthma regimen (30 mg/month 3 times then every 2 months) was used in 63/66 patients (95%). Sixteen patients (24%) were concomitantly treated with another immunosuppressant.

Median follow-up after initiation of benralizumab was 23 months (IQR 9-34). Thirty-three patients (49%) had a complete response, 24 (36%) had a partial response and 10 (15%) failed to respond (response assessed in 67 patients). Of 57 patients with at least a partial initial response, 10 (18%) experienced secondary failure. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with more primary failure (p=0.034) and less GC discontinuation (p=0.001).

Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or ANCA positivity at benralizumab initiation (p=0.010). Six infections requiring specific treatments were reported during follow-up.

Conclusion: Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows glucocorticoid withdrawal. However, its efficacy was lower after prior mepolizumab failure.

Response to benralizumab (A) and failure to benralizumab (B) among patients with eosinophilic granulomatosis with polyangiitis, according to previous treatment by mepolizumab. Variation in disease activity using the Birmingham Vasculitis Activity Score (BVAS) (C), daily dose of prednisone (D), variation in the forced expiratory volume in 1 second (FEV1) (E) and eosinophils count (F) among patients with eosinophilic granulomatosis with polyangiitis treated with benralizumab, according to previous treatment by mepolizumab. Accumulated proportions of patient with at least one asthma exacerbations during follow-up (G). Values in C, D, E, and F are the median and interquartile range.
IS = immunosuppressant; * = P < 0.05; ** = P < 0.01 (Fisher exact test).

Kaplan-Meier survival curve of complete response (A) and withdrawal of glucocorticoids (B) among patients with eosinophilic granulomatosis with polyangiitis treated with benralizumab, according to previous treatment by mepolizumab. Blue full line = without previous mepolizumab; green dotted line = with previous mepolizumab. (Logrank test)

Disclosures: A. Cottu: None; M. Groh: AstraZeneca, 6, GSK, 6, Sanofi, 6; C. Desaintjean: None; S. Marchand-Adam: None; L. Guillevin: None; X. Puéchal: None; E. Lazaro: None; M. Samson: ARGENX, 2, Boehringer-Ingelheim, 2, CHUGAI, 2, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2, NOVARTIS, 2, 5; C. Taillé: AstraZeneca, 6, Chiesi, 5, 6, GSK, 5, 6, Novartis, 5, 6, Sanofi, 6; C. Durel: None; E. Diot: None; S. Nicolas: None; L. Guilleminault: None; M. Ebbo: None; P. Cathébras: None; C. Dupin: AstraZeneca, 6, GSK, 6; H. Yildiz: GSK, 6; N. Belfeki: None; G. Pugnet: None; P. Chauvin: None; S. Jouneau: None; F. Lifermann: None; J. Martellosio: None; V. Cottin: Boehringer Ingelheim, 2, 5, 6, 12, Support for attending meetings, Celgene/BMS, 1, 2, CSL Behring, 2, Ferrer, 2, 6, 12, Support for attending meetings, FibroGen, 1, Galapagos, 1, 2, Galecto, 1, GlaxoSmithKline, 2, Pliant, 2, Pure Tech, 2, Redx, 2, Roche, 1, 2, 6, 12, Support for attending meetings, Sanofi, 2, Shionogi, 2; B. Terrier: AstraZeneca, 5, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2.

To cite this abstract in AMA style:

Cottu A, Groh M, Desaintjean C, Marchand-Adam S, Guillevin L, Puéchal X, Lazaro E, Samson M, Taillé C, Durel C, Diot E, Nicolas S, Guilleminault L, Ebbo M, Cathébras P, Dupin C, Yildiz H, Belfeki N, Pugnet G, Chauvin P, Jouneau S, Lifermann F, Martellosio J, Cottin V, Terrier B. Benralizumab in Eosinophilic Granulomatosis with Polyangiitis [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/benralizumab-in-eosinophilic-granulomatosis-with-polyangiitis/. Accessed .

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