Glucocorticoids versus Glucocorticoids Plus Cyclophosphamide in Eosinophilic Granulomatosis with Polyangiitis Without Poor-Prognosis Factors: A Target Trial Emulation Study

Boris Sorin¹, Matthias Papo¹, Renato Alberto Sinico², Vítor Silvestre Teixeira³, Nils Venhoff⁴, Maria-Letizia Urban⁵, Michele Iudici⁶, Juliane Mahrhold⁷, Francesco Locatelli⁸, Giulia Cassone⁹, Franco Schiavon¹⁰, Benjamin Seeliger¹¹, Thomas Neumann¹², Claudia Feder¹³, Claus Kroegel¹⁴, Matthieu Groh¹⁵, Chiara Marvisi¹⁶, Maxime Samson¹⁷, Thomas Barba¹⁸, David Jayne¹⁹, Arianna Troilo²⁰, Jens Thiel²⁰, Bernhard Hellmich²¹, Sara Monti²², Carlomaurizio Montecucco²³, Carlo Salvarani²⁴, Jean-Emmanuel Kahn²⁵, Bernard Bonnotte²⁶, Cécile-Audrey Durel²⁷, Xavier Puéchal²⁸, Luc Mouthon²⁹, Loïc Guillevin³⁰, Giacomo Emmi³¹, Augusto Vaglio³², Raphael Porcher³³ and Benjamin Terrier³⁴, and the French Vasculitis Study Group (FVSG) and the European EGPA Study Group (EESG), ¹Department of Internal Medicine, Cochin Hospital, National Referral Center for Rare Systemic Autoimmune and Autoinflammatory Diseases of Ile de France, East and West, Paris Cité University, Assistance Publique – Hôpitaux de Paris, Paris, France, ²Nephrology and Dialysis Unit, IRCCS Humanitas Research Hospital, Milan, Italy, ³Department of Rheumatology, Faro Hospital, Algarve, Portugal, ⁴Medical Center - University of Freiburg, Internal Medicine, Department of Rheumatology and Clinical Immunology, Freiburg, Germany, ⁵Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, ⁶Department of Internal Medicine, Cochin Hospital, National Referral Center for Rare Systemic Autoimmune and Autoinflammatory Diseases of Ile de France, East and West, Paris Cité University, Assistance Publique – Hôpitaux de Paris and Division of rheumatology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland, Paris, France, ⁷Department of Internal Medicine, Rheumatology, Pulmonology, Nephrology and Diabtologyy and Immunology, ERN-RITA Reference Center, Vasculitis-Center Tübingen-Kirchheim, Medius Kliniken Kirchheim, University of Tübingen, Kirchheim-Teck, Germany, ⁸Department of Rheumatology, IRCCS Policlinico S. Matteo Foundation, University of Pavia, Pavia, Italy, ⁹Clinical and Experimental Medicine PhD Program, Azienda USL-IRCCS di Reggio Emilia and Universita di Modena and Reggio Emilia, Modena, Italy, ¹⁰Department of Medicine DIMED, Division of Rheumatology, University of Padua, Padua, Italy, ¹¹Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany, ¹²Department of Rheumatology, Clinic of Internal Medicine III, Jena University Hospital, Jena, Germany and Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St Gallen, St Gallen, Switzerland, Jena, Germany, ¹³Department of Rheumatology, Clinic of Internal Medicine III, Jena University Hospital, Jena, Germany, ¹⁴Department of Pneumology and Allergology, Clinic of Internal Medicine I, Jena University Hospital, Jena, Germany, ¹⁵Foch, Suresnes, France, ¹⁶Rheumatology Unit Universita di Modena and Reggio Emilia, Modena, Italy, ¹⁷Department of Internal Medicine and Clinical Immunology, François-Mitterrand Teaching Hospital, University of Bourgogne-Franche-Comté, Dijon, France, ¹⁸Department of Internal Medicine, Hôpital Edouard Herriot, Lyon, France, ¹⁹University of Cambridge, Cambridge, United Kingdom, ²⁰Department of Rheumatology and Clinical Immunology, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany, ²¹Klinik für Innere Medizin, Rheumatologie, Pneumologie, Nephrologie und Diabetologie, Medius Kliniken, Akademisches Lehrkrankenhaus der Universität Tübingen, Kirchheim unter Teck, Germany, ²²IRCCS Istituto Auxologico Italiano, Milan, Italy, ²³IRCCS policlinico S. Matteo foundation, University of Pavia, Pavia, Italy, ²⁴Azienda USL-IRCCS di Reggio Emilia and University of Modena and Reggio Emilia, Reggio Emilia, Italy, Reggio Emilia, Italy, ²⁵Department of Internal Medicine, Ambroise Paré Hospital, Assistance Publique - Hôpitaux de Paris, Université de Versailles Saint-Quentin-en-Yvelines, Boulogne-Billancourt, France, Boulogne Billancourt, France, ²⁶Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France., Dijon, France, ²⁷Edouard Herriot University Hospital, Lyon, France, ²⁸National Referral Center For Rare Systemic Autoimmune Diseases, Paris, France, ²⁹Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d'Ile de France de l'Est et de l'Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, ³⁰National Referral Center For Rare Systemic Autoimmune Diseases, Paris, Ile-de-France, France, ³¹Department of Medical, Surgery and Health Sciences, University of Trieste, and Clinical Medicine and Rheumatology Unit, Cattinara University Hospital, Trieste, Italy, ³²Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Firenze, Florence, Italy, ³³Department of Rheumatology, Bicêtre AP-HP Hôpital, Université Paris-Saclay, Paris, Ile-de-France, France, ³⁴Service de Médecine interne, Hôpital Cochin, AP-HP, Paris, Ile-de-France, France

Meeting: ACR Convergence 2024

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

Session Information

Date: Sunday, November 17, 2024

Title: Vasculitis – ANCA-Associated Poster II

Session Type: Poster Session B

Session Time: 10:30AM-12:30PM

Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, blood and tissue eosinophilia and vasculitis affecting multiple organs. According to the European recommendations, patients with EGPA without poor-prognosis factor are treated with glucocorticoids (GCs) alone. However, no study has ever compared GC versus GC plus CYC in patients without poor-prognosis factors as assessed by the 1996 Five Factor Score (FFS). Two different studies showed that the combination of GCs plus azathioprine or rituximab compared with GCs alone did not improve the remission rate in EGPA without poor-prognosis factors. In the present study, using a large retrospective European database, we compared the efficacy of GCs plus CYC versus GCs alone for the treatment of EGPA without poor-prognosis.

Methods: We emulated a target trial using observational data from a European multicenter retrospective database. We included patients with newly diagnosed EGPA with a 1996 Five Factor Score (FFS) of 0, treated with GCs or GCs plus CYC between June 1985 and November 2018. Primary outcome was overall relapse. Secondary outcomes were major relapse, death and GC-dependent asthma and/or ear nose and throat (ENT) manifestations. Propensity score analysis was used to adjust for potential confounders. We performed a subgroup analysis on patients with organ-threatening manifestations.

Results: A total of 250 patients were included: 113 (45%) were male and the mean age at diagnosis was 52 (± 15 years); 177 (71%) were treated with GCs alone and 73 (29%) with GCs plus CYC. Among these patients with a FFS of 0, 102 (41%) patients had organ-threatening manifestations (mainly mononeuritis multiplex in 96 patients): 59 were treated with GCs alone and 43 were treated with GCs plus CYC.

After weighting, the variables included in the propensity score estimation were balanced in the two groups and the risk of any relapse at 12 months (hazard ratio [HR]: 1.74, 95% CI [0.56-5.40], p =0.338), major relapse at 12 months (HR: 2.14, 95% CI [0. 56-8.17], p =0.267) and the proportion of GC-dependent asthma and/or ENT manifestations at 24 months (odds ratio [OR]: 1.73, 95% CI [0.96-3.08], p =0.068) were not statistically different in the GCs plus CYC group compared to the GCs alone group.

Similar results were observed in the subgroup of patients with a FFS of 0 but organ-threatening manifestations: HR for any relapse at 12 months: 0.88 (95%CI [0.26-3.03], p =0.839); HR for major relapse at 12 months: 1.04 (95%CI [0.28-3.85], p =0.951) and OR for GC-dependent asthma and/or ENT manifestations at 24 months: 1.79 (95%CI [0.77-4.16], p =0.175).

Three patients (2%) died before 12 months in the GCs group versus none in the GCs plus CYC group. Among the 146 patients for whom safety data were available at 24 months, 1 (1%) patient in the GCs group and 3 (6%) in the GCs plus CYC group had a severe infection and no patient developed cancer.

Conclusion: This target trial emulation study shows that the addition of CYC to GCs does not reduce the rate of vasculitis relapse or the rate of GC-dependent asthma and/or ENT manifestations in patients with EGPA and no poor-prognosis factors, including patients with organ-threatening manifestations.

Disclosures: B. Sorin: None; M. Papo: None; R. Sinico: None; V. Teixeira: None; N. Venhoff: AbbVie/Abbott, 1, 5, 6, AstraZeneca, 1, 6, Boehringer-Ingelheim, 1, 6, Bristol-Myers Squibb(BMS), 6, Celgene, 6, Chugai, 6, GlaxoSmithKlein(GSK), 1, 6, Janssen, 1, 6, Medac, 5, Novartis, 1, 5, 6, Pfizer, 1, 5, 6, Roche, 1, 6, UCB, 1, 6, Vifor, 1, 6; M. Urban: None; M. Iudici: None; J. Mahrhold: None; F. Locatelli: None; G. Cassone: None; F. Schiavon: None; B. Seeliger: None; T. Neumann: None; C. Feder: None; C. Kroegel: None; M. Groh: None; C. Marvisi: None; M. Samson: None; T. Barba: None; D. Jayne: Amgen, 2, 6, AstraZeneca, 2, 6, Aurinia, 4, Boehringer Ingelheim, 2, 6, Bristol-Myers Squibb(BMS), 2, 6, ChemoCentryx, 2, 6, Chinook, 1, CSL Vifor, 2, GSK, 1, 2, 6, Novartis, 2, 6, Roche, 2, 6, Takeda, 1, 2, 6, Vifor Pharma, 2, 6; A. Troilo: None; J. Thiel: None; B. Hellmich: AbbVie, 2, 6, Amgen, 2, 6, AstraZeneca, 2, 6, Boehringer-Ingelheim, 2, 6, Bristol Myers Squibb, 2, 6, Chugai, 2, 6, GlaxoSmithKline, 2, 6, InflaRx, 2, 6, Janssen, 2, 6, MSD, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, Phadia, 2, 6, Roche, 2, 6, Vifor Pharma, 2, 6; S. Monti: AstraZeneca, 6, GlaxoSmithKlein(GSK), 6; C. Montecucco: None; C. Salvarani: None; J. Kahn: None; B. Bonnotte: None; C. Durel: None; X. Puéchal: None; L. Mouthon: None; L. Guillevin: None; G. Emmi: None; A. Vaglio: None; R. Porcher: None; B. Terrier: AstraZeneca, 2, GlaxoSmithKline, 2, Novartis, 2, Vifor Pharma, 2.

To cite this abstract in AMA style:

Sorin B, Papo M, Sinico R, Teixeira V, Venhoff N, Urban M, Iudici M, Mahrhold J, Locatelli F, Cassone G, Schiavon F, Seeliger B, Neumann T, Feder C, Kroegel C, Groh M, Marvisi C, Samson M, Barba T, Jayne D, Troilo A, Thiel J, Hellmich B, Monti S, Montecucco C, Salvarani C, Kahn J, Bonnotte B, Durel C, Puéchal X, Mouthon L, Guillevin L, Emmi G, Vaglio A, Porcher R, Terrier B. Glucocorticoids versus Glucocorticoids Plus Cyclophosphamide in Eosinophilic Granulomatosis with Polyangiitis Without Poor-Prognosis Factors: A Target Trial Emulation Study [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/glucocorticoids-versus-glucocorticoids-plus-cyclophosphamide-in-eosinophilic-granulomatosis-with-polyangiitis-without-poor-prognosis-factors-a-target-trial-emulation-study/. Accessed .

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