Long-term Efficacy of Remission-induction Regimens for Eosinophilic Granulomatosis with Polyangiitis

Martin Dutertre¹, Gregory Pugnet², Claire De Moreuil³, Bernard Bonnotte⁴, YGAL BENHAMOU⁵, Dominique Chauveau⁶, Elisabeth Diot⁷, Pierre Duffau⁸, Nicolas Limal⁹, Antoine Néel¹⁰, GEOFFREY URBANSKI¹¹, Noémie Jourde-Chiche¹², Nicolas MARTIN SILVA¹³, Francois Maurier¹⁴, Arsène Mekinian¹⁵, Nicolas Schleinitz¹⁶, Felix ackermann¹⁷, Anne-Laure Fauchais¹⁸, Antoine Froissart¹⁹, Thomas Le Gallou²⁰, Yurdagul Uzunhan²¹, Jean-Francois Viallard²², Alice Berezne²³, laurent chiche²⁴, Bruno Crestani²⁵, Guillaume Direz²⁶, Cecile-Audrey DUREL²⁷, Pascal Godmer²⁸, Jean-Emmanuel Kahn²⁹, Marc Lambert³⁰, Mathilde de Menthon¹, Thomas Quemeneur³¹, Jacques Cadranel¹, Pierre Charles³², Antoine Dossier¹, Loic Guillevin³³, Xavier Puéchal³⁴ and Benjamin Terrier³⁵, ¹AP-HP, Paris, France, ²CHU Toulouse Rangueil Service de Medecine Interne et Immunologie Clinique, Toulouse, France, ³CHU de Brest, Brest, France, ⁴Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France, ⁵rouen university hospital, Rouen, France, ⁶Hôpital Le Tripode, Bordeaux, France, ⁷Service de médecine interne et immunologie clinique, CHU Tours, Tours, France, ⁸CHU Bordeaux, Bordeaux, France, ⁹AP-HP, Créteil, France, ¹⁰CHU de Nantes, Nantes, France, ¹¹CHU Angers, Angers, France, ¹²AP-HM, Marseille, France, ¹³CHU Caen, Caen, France, ¹⁴Hôpitaux privés de Metz, Vaux / Frankreich, France, ¹⁵Department of Internal Medicine, Hôpital Saint-Antoine, AP-HP, Paris, France, ¹⁶Aix Marseille university, AP-HM, Marseille, France, ¹⁷Hôpital Foch, Suresnes, France, ¹⁸Dupuytren Hospital, Limoges, France, ¹⁹CHI Créteil, Créteil, France, ²⁰CHU Rennes, Rennes, France, ²¹AP-HP, Bobigny, France, ²²CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France, ²³CH Annecy, Annecy, France, ²⁴Hopital Europeen, Marseille, France, ²⁵Hopital Bichat, Paris University, Paris, France, ²⁶CH Le Mans, Le Mans, France, ²⁷Hospices Civils de Lyon, Lyon, France, ²⁸CH Bretagne Atlantique, Vannes, France, ²⁹AP-HP, Suresnes Cedex, France, ³⁰CHRU Lille, Lille, France, ³¹CH Valenciennes, Valenciennes, France, ³²Institut Mutualiste Montsouris, Service de Médecine Interne, Paris, France, ³³University Paris Descartes, Paris, France, ³⁴National Referral Center for Rare Systemic Autoimmune Diseases, Paris, France, ³⁵Department of Internal Medicine, Hôpital Cochin, AP-HP, Paris, France

Meeting: ACR Convergence 2023

Keywords: ANCA, ANCA associated vasculitis, Eosinophilic Granulomatosus with Polyangiitis (Churg-Strauss), Myocarditis

Session Information

Date: Sunday, November 12, 2023

Title: Abstracts: Vasculitis – ANCA-Associated I

Session Type: Abstract Session

Session Time: 4:00PM-5:30PM

Background/Purpose: The Rituximab in Eosinophilic Granulomatosis With Polyangiitis (REOVAS) trial compared rituximab (RTX) infusions to conventional strategy for remission-induction in eosinophilic granulomatosis with polyangiitis (EGPA). This trial failed to show a superiority of RTX over the conventional strategy to induce remission at 180 days. However, the long-term efficacy and safety of RTX as compared with conventional strategy in EGPA remains unknown. We report here the long-term results of the REOVAS trial.

Methods: After completion of the 12-month REOVAS trial, patients were followed prospectively, with data on disease activity, medications and adverse events collected by the patients’ physicians every 6 months until the last follow-up. The primary endpoint was the minor and major relapse-free survival. Secondary endpoints were major relapses and asthma and ENT exacerbations were also assessed.

Results: Among 105 enrolled patients, only one was lost to follow-up. The median follow-up was 45 months (IQR 34-53).

At month 45 (median follow-up), for the RTX and conventional strategy arms, respectively, the minor and major relapse-free survival rates were 63.5% (95%CI 49.9%-75.2%) and 50.9% (95%CI 37.9%-63.9%) (p=0.24) ; major relapse-free survival rates were 90.4% (95%CI 79.4%-95.8%) and 79.2% (95%CI 66.5%-88.0%) (p=0.17); asthma and/or ENT exacerbation-free survival rates were 42.3% (95%CI 29.9%-55.8%) and 34.0% (95%CI 22.7%-47.4%) (p=0.42) ; and overall EGPA-related event-free survival rates were 32.7% (95%CI 21.5%-46.2%) and 22.6% (95%CI 13.5%-35.5%) (p=0.28). We then focused our analysis on patients with MPO-ANCA and showed that the minor and major relapse-free survival rates were 92.3% (95% CI 66.7% – 99.6%) and 50% (95% CI 58% – 72%) for the RTX and conventional arms, respectively (p=0.02).

As 39 patients were enrolled during follow-up in the double-blind MAINRITSEG trial evaluating RTX versus azathioprine for maintenance in EGPA, we focused our analysis on the 66 patients (63%) who were not enrolled in MAINRITSEG. At month 45, the minor and major relapse-free survival rates for the RTX (n=30) and conventional strategy (n=36) arms were 60.0% (95%CI 42.3%-75.4%) and 38.9% (95%CI 24.8%-55.2%), respectively (p=0.14), and the major relapse-free survival rates were 90.0% (95%CI 73.6%-97.3%) and 72.2% (95%CI 55.9%-84.3%), respectively (p=0.12). When analyzing only ANCA-positive patients (14 in the RTX and 14 in the conventional arms), the minor and major relapse-free survival rates were 78.6% (95%CI 51.7%-93.2%) and 35.7% (95%CI 16.2%-61.4%), respectively (p=0.054). Similar results were found when analyzing only MPO-ANCA positive patients (6 in the RTX and 9 in the conventional arms), showing that minor and major relapse-free survival rates were 100.0% (95%CI 55.7%-100.0%) and 22.22% (95%CI 5.3%-55.7%), respectively (p=0.007).

Conclusion: Among EGPA patients with active disease, long-term follow-up supports that RTX and the conventional strategy have similar efficacy in inducing and maintaining remission. However, in ANCA-positive patients, RTX was associated with a better relapse-free survival compared to the conventional strategy.

Figure 1. Kaplan-Meier curves of the risk of all (major and minor) relapse (A), major relapse (B) in all patients; all relapse (C) and major relapse (D) in MPO-ANCA-positive patients, according to treatment group.
Patients were randomly assigned to receive remission induction therapy with rituximab strategy or conventional strategy, stratified according to disease-flare category, ANCA positivity and the Five Factor score

Table 1. Baseline characteristics of the patients included in the REOVAS study

Table 2. Numbers of patients with SAE according to treatment group

Disclosures: M. Dutertre: None; G. Pugnet: None; C. De Moreuil: None; B. Bonnotte: None; Y. BENHAMOU: None; D. Chauveau: None; E. Diot: None; P. Duffau: None; N. Limal: None; A. Néel: None; G. URBANSKI: None; N. Jourde-Chiche: None; N. MARTIN SILVA: None; F. Maurier: None; A. Mekinian: None; N. Schleinitz: CSL behring, 1, Eusapharma, 6, GSK, 6; F. ackermann: None; A. Fauchais: None; A. Froissart: None; T. Le Gallou: None; Y. Uzunhan: None; J. Viallard: None; A. Berezne: None; l. chiche: None; B. Crestani: None; G. Direz: None; C. DUREL: None; P. Godmer: None; J. Kahn: None; M. Lambert: None; M. de Menthon: None; T. Quemeneur: None; J. Cadranel: None; P. Charles: None; A. Dossier: None; L. Guillevin: None; X. Puéchal: None; B. Terrier: AstraZeneca, 5, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2.

To cite this abstract in AMA style:

Dutertre M, Pugnet G, De Moreuil C, Bonnotte B, BENHAMOU Y, Chauveau D, Diot E, Duffau P, Limal N, Néel A, URBANSKI G, Jourde-Chiche N, MARTIN SILVA N, Maurier F, Mekinian A, Schleinitz N, ackermann F, Fauchais A, Froissart A, Le Gallou T, Uzunhan Y, Viallard J, Berezne A, chiche l, Crestani B, Direz G, DUREL C, Godmer P, Kahn J, Lambert M, de Menthon M, Quemeneur T, Cadranel J, Charles P, Dossier A, Guillevin L, Puéchal X, Terrier B. Long-term Efficacy of Remission-induction Regimens for Eosinophilic Granulomatosis with Polyangiitis [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/long-term-efficacy-of-remission-induction-regimens-for-eosinophilic-granulomatosis-with-polyangiitis/. Accessed .

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