Matthias Papo1, Pauline Martinot2, Renato A. Sinico3, Vitor Teixeira4, Nils Venhoff5, Maria-Letizia Urban6, Juliane Mahrhold7, Francesco Locatelli8, Giulia Cassone9, Franco Schiavon10, Benjamin Seeliger11, Thomas Neumann12, Claus Kroegel13, Matthieu Groh14, Chiara Marvisi15, Maxima Samson16, Thomas Barba17, David Jayne18, Arianna Troilo19, Jens Thiel20, Bernhard Hellmich21, Sara Monti22, Carlomaurizio Montecucco8, Carlo Salvarani23, Jean-Emmanuel Kahn24, Cecile-Audrey DUREL25, Luc Mouthon26, Loïc Guillevin26, Giacomo Emmi27, Augusto Vaglio28, Raphaël Porcher29 and Benjamin Terrier26, 1Service De Médecine Interne - Hôpital Cochin, Paris, France, 2Centre of Research in Epidemiology and Statistics, Université de Paris, Paris, Île-de-France, France, Paris, 3Department of Medicine and Surgery, Università degli Studi di Milano – Bicocca, Italy, Milano, Italy, 4Hospital de Faro, CHUA, Lisbon, Portugal, 5Department of Rheumatology and Clinical Immunology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany, 6Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy, 7Department of Internal Medicine, Rheumatology and Immunology, Medius Kliniken, University of Tübingen, Kirchheim Teck, Germany, 8Department of Rheumatology, IRCCS Policlinico S. Matteo Foundation, University of Pavia, Pavia, Italy, 9Università di Modena e Reggio Emilia, Modena, Italy, 10Operative Unit of Rheumatology, Department of Medicine DIMED, University of Padova, Padova, Italy, 11Department of Respiratory Medicine, Hannover Medical School, Wermsdorf, Germany, 12Kantonsspital St. Gallen, St. Gallen, Switzerland, 13Department of Pneumology and Allergology, Clinic of Internal Medicine I, Jena University Hospital, Jena, Germany, 14Service de Médecine Interne, Centre de Référence des Syndromes Hyperéosinophiliques-CEREO, Hôpital Foch, Université Versailles–Saint-Quentin-en-Yvelines, Suresnes, France, 15Università di Modena e Reggio Emilia and National Institute of Arthritis & Musculoskeletal & Skin Diseases, National Institutes of Health, Bethesda, MD, 16Dijon University Hospital, Dijon, France, 17Department of Internal Medicine, Hôpital Edouard Herriot, Lyon, France, 18University of Cambridge, Cambridge, United Kingdom, 19Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, 20University Hospital Freiburg, Freiburg, Germany, 21Klinik für Innere Medizin, Rheumatologie & Immunologie, Medius Kliniken, Universität Tübingen, Plochingen, Germany, 22Rheumatology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy, 23Azienda USL -IRCCS di Reggio Emilia and Università di Modena e Reggio Emilia, Reggio Emilia, Reggio Emilia, Italy, 24Service de médecine interne - Hôpital Ambroise Paré, AP-HP, Boulogne-Billancourt, France, 25CHU Lyon, Lyon, France, 26National Referral Center for Rare Systemic Autoimmune Diseases, Cochin Hospital, Paris, France, 27Azienda Ospedaliero Universitaria Careggi, Firenze, Italy, 28Azienda Ospedaliero Universitaria Meyer, Parna, Italy, 29Université Paris Cité, Hôtel-Dieu, Paris, France
Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) is a small vessel necrotizing vasculitis characterized by blood and tissue eosinophilia and asthma. Glucocorticoids (GCs) frequently control the disease, but relapses and/or GC-dependency are frequent. Evolving concepts distinguish vasculitis-related symptoms from asthma and/or ENT manifestations. That distinction has become even more important since the development of B-cell and eosinophil-targeted therapies. Our objective was to build models to predict the evolution towards a relapse of vasculitis or towards a GC-dependent asthma and/or ENT manifestations.
Methods: We set up a multicenter European retrospective study of EGPA patients. EGPA diagnosis was made according to ACR and/or MIRRA criteria. We developed a multivariable prediction model using the PMSAMPSIZE algorithm: one model for the vasculitis relapse risk during follow-up (excluding asthma and/or ENT manifestations) and one model for the risk of GC-dependent asthma and/or ENT manifestations at two years of follow-up.
Results: We included 809 patients. Patients' middle age was 52 (+/- 14.8) years, and median follow-up was of 72 months (IQR 37/115). During follow-up, 228 experienced at least one vasculitis relapse, with a cumulative incidence at 12 years of 41.2% (95% CI 36.3-46.8). At two years of follow-up, 66.4% of patients had GC-dependent asthma and/or ENT manifestations.
First, a model predicting the risk of vasculitis relapse included the following variables: age at diagnosis (nonlinear effect), GC-dependent asthma before EGPA diagnosis (HR 1.57 [1.24-2.55]), arthralgia (HR 1.27 [1.01-1.60]), myocarditis (HR 1.74 [1.16-2.62]), peripheral neuropathy (HR 1.39 [1.09-1.79]), MPO-ANCA (HR 1.56 [1.22-2.01]) and baseline eosinophils count (nonlinear effect]). Final model allowed to modelize a nomogram and calculate a score establishing the vasculitis relapse risk at 5 and 12 years of follow-up.
Second, a predicting the risk of GC-dependent asthma and/or ENT manifestations at 2 years included the following variables: age at diagnosis (per year, OR 0.98 [0.97-0.99]), GC-dependent asthma at EGPA diagnosis (OR 1.50 [1.02-2-20]), history of chronic sinusitis before EGPA diagnosis (OR 1.78 [1.27-2.48]), and baseline eosinophils count (per 10.109/L, OR 0.70 [0.49-1.00]). Final model allowed to modelize a nomogram and calculate a score establishing the risk of GC-dependent asthma and/or ENT manifestations at 2 years.
Conclusion: Through a large retrospective European EGPA cohort, we developed models predicting the vasculitis relapse risk and the risk of GC-dependent asthma and/or ENT manifestations at 2 years. These models must be validated in validation cohorts and could be used to guide the use of biotherapies targeting B cells or eosinophils.
Disclosures: M. Papo, None; P. Martinot, None; R. Sinico, None; V. Teixeira, None; N. Venhoff, None; M. Urban, None; J. Mahrhold, None; F. Locatelli, None; G. Cassone, None; F. Schiavon, None; B. Seeliger, None; T. Neumann, None; C. Kroegel, None; M. Groh, None; C. Marvisi, None; M. Samson, None; T. Barba, None; D. Jayne, Aurinia, AstraZeneca, GlaxoSmithKline (GSK), Roche/Genentech, Vifor, Bristol-Myers Squibb(BMS), Chemocentryx, Novartis, Takeda, Boehringer-Ingelheim, Otsuka, UCB, Amgen, Kessai; A. Troilo, None; J. Thiel, None; B. Hellmich, AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb (BMS), Boehringer-Ingelheim, Chugai, GlaxoSmithKline (GSK), InflaRx, Janssen, MSD, Novartis, Pfizer, Phadia, Roche, Vifor; S. Monti, None; C. Montecucco, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Eli Lilly, Gilead, Roche, Pfizer, Sanofi; C. Salvarani, None; J. Kahn, None; C. DUREL, None; L. Mouthon, Boehringer-Ingelheim, LFB; L. Guillevin, Roche; G. Emmi, None; A. Vaglio, None; R. Porcher, None; B. Terrier, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb(BMS), Eli Lilly, LFB, Boehinger Ingelheim, Vifor Pharma, Pfizer, Roche.
