POS0870 THERAPEUTIC STRATEGY IN NEUROSARCOIDOSIS: COMPARISON OF THE EFFICACY OF CYCLOPHOSPHAMIDE, INFLIXIMAB AND METHOTREXATE. RETROSPECTIVE MULTICENTER STUDY OF 40 CASES
Authors: H. Gomez, J. Schmidt, V. Langlois, A. Aouba, M. Avenel, B. Bourre, H. Levesque, Y. Benhamou, M. Leclercq
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Neurosarcoidosis is a rare and severe manifestation, affecting between 3% and 15% of patients with sarcoidosis. The cornerstone of treatment is corticosteroid therapy. Several drug are available in the therapeutic arsenal: Cyclophosphamide (CYC), anti-TNFα biotherapy, conventional immunosuppressants, in particular Methotrexate (MTX). However, the current therapeutic strategy is not clearly defined. <h3>Objectives:</h3> The primary endpoint was relapse, defined as an increase of at least 1 point of the Extrapulmonary Organ Severity Tool (ePOST) score after initial improvement. Secondary endpoints included therapeutic response, cortisone sparing and adverse events. <h3>Methods:</h3> We conducted a French multicenter retrospective study. Patients with definite or probable neurosarcoidosis (histologically proven sarcoidosis and presence of a neurological localization) were divided into 3 groups according to the treatment received: CYC group, infliximab (IFX) group and MTX group. <h3>Results:</h3> 403 cases were screened, 40 patients (11 treated with CYC, 8 treated with IFX and 21 treated with MTX) were included, predominantly male (53%) with a median age of 43 years. Preferred neurological locations were the meninges (50%), cranial nerves (52%) and encephalon (55%). Twelve patients suffered a relapse: 7 (58%) on CYC, 1 (8%) on IFX and 4 (33%) on MTX. The overall relapse-free survival rate was 97.5% at 6 months, 85% at 1 year and 76% at 2 years. Relapse-free survival medians differed statistically between the 3 groups (p = 0.02), with a median survival for the CYC group of 36 months, while median survival for the IFX and MTX groups could not be calculated due to lack of occurrence of the relapse event. Relapse was more frequent in the CYC subgroup (Odds ratio = 7.8, CI95 [1.4-53], p = 0.007). Relapse was associated with cerebral location (p = 0.03), multi-system involvement of sarcoidosis (p = 0.03) and young age (p = 0.02). Thirty-six patients (90%) were classified as responders at 12 months of treatment, reflected by a decrease in the initial ePOST score from 3 [3-4] to 1 [0-2]. There was no statistical difference in therapeutic response between the 3 groups. A significant decrease in corticosteroid therapy was observed in all 3 treatment groups, with no statistical difference between them. Infections were more frequent with CYC (p = 0.03) and rash were associated with IFX (p=0.02). <h3>Conclusion:</h3> Our study shows that Infliximab and Methotrexate are two effective therapeutic options for relapse prevention in neurosarcoidosis. Today, Cyclophosphamide, the historic treatment for severe sarcoidosis, appears to be a third-line choice, given the risk of relapse and its tolerability profile <h3>REFERENCES:</h3> [1] Sève P, Pacheco Y, Durupt F, Jamilloux Y, Gerfaud-Valentin M, Isaac S, et al. Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis. Cells. 31 mars 2021;10(4):766. [2] Kidd DP. Neurosarcoidosis: clinical manifestations, investigation and treatment. Practical Neurology. 1 mai 2020;20(3):199-212. [3] Stern BJ, Royal W III, Gelfand JM, Clifford DB, Tavee J, Pawate S, et al. Definition and Consensus Diagnostic Criteria for Neurosarcoidosis: From the Neurosarcoidosis Consortium Consensus Group. JAMA Neurology. 1 déc 2018;75(12):1546-53. [4] Joubert B, Chapelon-Abric C, Biard L, Saadoun D, Demeret S, Dormont D, et al. Association of Prognostic Factors and Immunosuppressive Treatment With Long-term Outcomes in Neurosarcoidosis. JAMA Neurol. nov 2017;74(11):1336-44. [5] Bitoun S, Bouvry D, Borie R, Mahevas M, Sacre K, Haroche J, et al. Treatment of neurosarcoidosis: A comparative study of methotrexate and mycophenolate mofetil. Neurology. 13 déc 2016;87(24):2517-21. [6] Fritz D, Timmermans WMC, van Laar JAM, van Hagen PM, Siepman TAM, van de Beek D, et al. Infliximab treatment in pathology-confirmed neurosarcoidosis. Neurol Neuroimmunol Neuroinflamm. sept 2020;7(5):e847. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>