0436: Clinical Characteristics and Outcome of ANCA-Associated Vasculitides Induced by Anti-Thyroid Drugs: A Multicenter Retrospective Cohort Study

Julien Culerrier¹, Yann Nguyen², Omer Karadag³, Sule Yasar Bilge⁴, Tuba DEMIRCI YILDIRIM⁵, Tahir Saygin Öğüt⁶, Veli Yazisiz⁶, Cemal Bes⁷, Ayse Cefle⁸, Oznur Sadioglu Cagdas⁹, Ayten Yazici⁸, Andreas Kronbichler¹⁰, David Jayne¹⁰, Alexis Regent¹¹, Vitor Teixeira¹², Sylvain Marchand-Adam¹³, PIerre Duffau¹⁴, Saskia Oro¹⁵, Baptiste Andre¹⁶, Luminita Luca¹⁷, Sarah Lechtman¹⁸, Achille Aouba¹⁹, Celine Lebas²⁰, Amélie Servettaz²¹, Amandine Dernoncourt²², Marc Ruivard²³, Anne-Marie Milesi²⁴, Vincent Poindron²⁵, Patrick Jego²⁶, Roberto Padoan²⁷, Paolo Delvino²⁸, Frédéric Vandergheynst²⁹, Christian Pagnoux³⁰, Elaine Yacyshyn³¹, Peter Lamprecht³², Oliver Flossmann³³, Xavier Puéchal¹¹ and Benjamin Terrier¹¹, ¹Université Paris Cité, Paris, France, Paris, France, ²AP-HP.Centre Universit Paris Cit Hôpital Cochin, Montmorency, France, ³Hacettepe University, Ankara, Turkey, ⁴Eskişehir Osmangazi Üniversity, Eskisehir, Turkey, ⁵Dokuz Eylul University, İzmir, Turkey, ⁶Akdeniz University, Antalya, Turkey, ⁷Bahçeşehi University, Istanbul, Turkey, ⁸Kocaeli University School of Medicine Division of Rheumatology, Kocaeli, Turkey, ⁹Kocaeli University, Kocaeli, Turkey, ¹⁰University of Cambridge, Cambridge, United Kingdom, ¹¹National Referral Center for Rare Systemic Autoimmune Diseases, Cochin Hospital, Paris, France, ¹²Hospital de Faro, CHUA, Lisbon, Portugal, ¹³Tours University Hospital, Tours, France, ¹⁴CHU Bordeaux, Bordeaux, France, ¹⁵Assistance Publique - Hôpitaux de Paris., Paris, France, ¹⁶Hôpital de la Timone, Marseille, Marseille, France, ¹⁷CHU de Poitiers, Poitiers, France, ¹⁸CHU Nice, Nice, France, ¹⁹Department of Internal Medicine, UR4650 PSIR, Normandie Univ, UNICAEN, CHU de Caen Normandie, Caen, France, ²⁰CHRU Lille, Lille, France, ²¹CHU Reims, Reims, France, ²²CHU Amiens - Picardie, Amiens, France, ²³Clermont Ferrand University Hospital, Clermont-Ferrand, France, ²⁴Centre hospitalier de Vichy, Vichy, France, ²⁵Immunologie clinique et médecine interne, Hôpitaux universitaires de Strasbourg, Strasbourg, France, ²⁶CHU Rennes, Paris, France, ²⁷University of Padova, Padova, Italy, ²⁸Università di Pavia, Vercelli, Italy, ²⁹Professeur de Médecine Interne et Sémiologie médicale, Directeur de la Clinique de Médecine Interne Générale, Université Libre de Bruxelles, Bruxelles, France, ³⁰Division of Rheumatology, Mount Sinai Hospital, Toronto, ON, Canada, ³¹University of Alberta, Edmonton, AB, Canada, ³²Department of Rheumatology University of Lübeck Ratzeburger Allee, Lübeck, Germany, ³³Royal Berkshire Hospital, Reading, United Kingdom

Background/Purpose: ANCA-associated vasculitides (AAV) induced by anti-thyroid drugs (ATD) is a well-known entity. However, characteristics, requirement for immunosuppressive agents and the risk of relapse remain poorly studied. We aimed to describe the clinical characteristics and outcome of patients with ATD-induced AAV in comparison to primary AAV.

Methods: We performed a retrospective multicenter study of patients with ATD-induced. ATD-induced AAV were defined as the development of AAV after ATD initiation until one year after ATD discontinuation. Patients were classified as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) according to 2022 ACR/EULAR classification criteria. We further focused on MPA patients and compared patients with ATD-induced MPA and those with primary MPA. Each ATD-induced MPA was matched with 4 primary MPA on gender and year of diagnosis. Baseline characteristics and treatments were compared with t-tests for continuous variables, and chi-2 tests for categorical variables. Remission-free-survivals were compared with Cox proportional hazard ratios models, adjusted on age at MPA diagnosis and on renal involvement.

Results: Forty-six patients with ATD-induced AAV were included. Twenty-eight (60%) fulfilled criteria for MPA, 8 (17%) criteria for GPA, one (2%) criteria for EGPA, and nine (19%) patients had unclassified AAV. Among the 46 patients, 97% were ANCA-positive, including MPO-ANCA in 22 (47%), PR3-ANCA in 6 (13%), and both MPO- and PR3-ANCA in 15 (32%). Main clinical manifestations were skin (65%), arthralgia (52%), and glomerulonephritis (34%).. At diagnosis, 1966 Five Factor Score was 0 for 81%, 1 for 4% and 2 for 15% of the patients.Therapeutic management was based on ATD discontinuation in 97% of cases, allowing vasculitis remission in 17%. Eighty-three percent of patients required an induction regimen including glucocorticoids in 100%, in combination with rituximab in 30% and cyclophosphamide in 19%. Maintenance therapy was initiated in 91% of the patients, mainly based on glucocorticoids. Anti-thyroid drugs were reintroduced in 8 cases (17%) and patients did not experience any relapse.

Patients with ATD-induced MPA (n=28) were compared with 112 matched primary MPA. Compared with primary MPA, ATD-induced MPA were significantly younger at diagnosis (49 vs. 65 years, P< 0.001), had less frequent renal involvement (43 vs. 76%, P=0.02), but more frequently cutaneous (53 vs. 25%, P=0.007) and ocular involvement (14.3 vs. 2.7%, P=0.042). ATD-induced MPA had a lower mean BVAS (9.9 vs. 13.1, P=0.023) at diagnosis. Finally, the risk of relapse was lower in ATD-induced MPA than in primary MPA (adjusted HR 0.07; 95%CI 0.01-0.62, P=0.016) (Figure).

Conclusion: In this multicenter retrospective cohort, ATD-induced AAV were mainly MPA with MPO-ANCA, but double MPO- and PR3-ANCA positivity was frequent. ATD-induced MPA were less severe and showed a lower risk of relapse than primary MPA.

Figure. Kaplan Meier showing relapse free survival by the time of AAV diagnosis in in the two groups.
Disclosures: J. Culerrier, None; Y. Nguyen, None; O. Karadag, None; S. Bilge, None; T. DEMIRCI YILDIRIM, None; T. Öğüt, None; V. Yazisiz, None; C. Bes, None; A. Cefle, None; O. Sadioglu Cagdas, None; A. Yazici, None; A. Kronbichler, None; D. Jayne, Aurinia, AstraZeneca, GlaxoSmithKline (GSK), Roche/Genentech, Vifor, Bristol-Myers Squibb(BMS), Chemocentryx, Novartis, Takeda, Boehringer-Ingelheim, Otsuka, UCB, Amgen, Kessai; A. Regent, None; V. Teixeira, None; S. Marchand-Adam, None; P. Duffau, None; S. Oro, None; B. Andre, None; L. Luca, None; S. Lechtman, None; A. Aouba, Roche; C. Lebas, None; A. Servettaz, None; A. Dernoncourt, None; M. Ruivard, Roche; A. Milesi, None; V. Poindron, None; P. Jego, None; R. Padoan, GlaxoSmithKlein(GSK); P. Delvino, None; F. Vandergheynst, None; C. Pagnoux, otsuka, AstraZeneca, Pfizer; E. Yacyshyn, None; P. Lamprecht, Vifor, GlaxoSmithKlein(GSK); O. Flossmann, None; X. Puéchal, Roche; B. Terrier, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb(BMS), Eli Lilly, LFB, Boehinger Ingelheim, Vifor Pharma, Pfizer, Roche.