BIOLOGICS AND JAK INHIBITORS EFFICACY IN VEXAS SYNDROME FROM FRENCH MULTICENTER CASE SERIES OF 256 PATIENTS

A. Mekinian, R. Bourguiba, B. Terrier, K. Olivier, T. Comont, P. Fenaux, S. Georgin-LavialleSaint Antoine, Internal Medicine, Paris, France Tunis CHU, Internal Medicine, Tunis, Tunisia Cochin, Intenral Medic, Paris, France Cochin, Internal Medicine, Paris, France Toulouse, Intenral Medic, Toulose, France Sainloiueoi, Hem, Paris, France Tenon Hospital, Internal Medicine, Paris, France  Background A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome. Objectives To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. Methods Case-series. Patients referred to a French multicenter registry between November 2020 and January 2022. Frequency and median of parameters and vital status, from diagnosis to the end of the follow-up. Results Among 256 patients, 207/221 (94%) were males with median age at diagnosis 65 years [49-86]. Main clinical features were skin lesions (n=215; 84%), non-infectious fever (n=121; 47%), lung involvement (n=146; 57%), relapsing chondritis (n=69; 27%), venous thrombosis (n=128; 50%), lymph nodes (n=55; 21%), and arthralgia (n=65; 25%) with arthritis (n=26). Ocular inflammatory involvement was present in 119 cases (46%), mainly uveitis (n=21) and scleritis/ episcleritis (n=43). Peripheral nervous system was noted in 18 patients (7%) with peripheral neuropathy (n=11), multinevritis (n=3) and PIDC (n=5). The skin lesions were mainly neutrophilic dermatosis (n=74) and vasculitis (n=45). Hematological disease was present myelodysplastic syndrome (MDS, n= 81; 32%), monoclonal gammapathy of unknown significance (n=18), chronic myelomonocytic leukemia (n=7). AA amyloidosis was present in 2 cases. Median CRP levels were at 56 [1-423] mg/l, with abnormal somatic mutations in 44 cases (%) mostly TET2 and DNMT3. Previous immunosuppressive therapies were methotrexate (n=15; 6%), cyclophosphamide (n=6; 3%), MMF (n=5; 4%). JAK inhibitors were used in 24 cases and were stopped in 5 cases (3 for inefficacy and 2 for adverse events). IL1R inhibitors were used in 12 cases with discontinuation for inefficacy (n=7) and adverse events (n=1), and IL6R inhibitors in 12 cases with discontinuation for inefficacy in 4 cases and adverse events in 1 cases. Conclusion This is the largest multicenter cohort of VEXAS syndrome and which allow to compare for the first time the efficacy and tolerance of various biologics and JAK inhibitors and seem confirm the benefit of JAKi and also of tocilizumab. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared. Keywords: Innate immunity, Adaptive immunity, Inflammatory arthritides DOI: 10.1136/annrheumdis-2023-eular.1756Citation: , volume 82, supplement 1, year 2023, page 1955Session: Other orphan diseases (Publication only)