Comparing the efficacy and safety of cyclophosphamide, infliximab and methotrexate in neurosarcoidosis: a multicenter retrospective study.

Introduction: Neurosarcoidosis is a granulomatous disease affecting 10% of patients with sarcoidosis. In lack of standardized guidelines, various therapeutic strategies exist. Beyond corticosteroids, cyclophosphamide, infliximab, or methotrexate are available options. This study compared the efficacy and safety of these agents as firstline therapy.

Methods: This multicenter, retrospective, study included patients with definite or probable neurosarcoidosis (1999-2022). Primary endpoint was relapse rate at the end of follow-up, after first-line therapy with cyclophosphamide, infliximab or methotrexate. Relapse was defined as a≥1-point increase in the Extrapulmonary Organ Severity Tool score following initial improvement.

Results: Fifty-two patients were included: 18 (34.6%) received cyclophosphamide, 10 (19.2%) infliximab and 24 (46.2%) methotrexate. Multivisceral impairment was observed in 63% of patients, and neurological involvement at diagnosis in 67% of patients. Main neurological localizations were the brain (60%), meninges (48%) and cranial nerves (46%). Sixteen patients (30.7%) relapsed: 56% with cyclophosphamide, 6% with infliximab and 38% with methotrexate (p = 0.06). Median relapse-free survival was 48 months in patients treated with cyclophosphamide, and not estimable for infliximab or methotrexate (p = 0.07). Relapse was associated with brain involvement (p = 0.006) and younger age (p = 0.04). At 12 months, response rate was 100% for infliximab-treated patients, 89% for cyclophosphamide and 87% for methotrexate. All treatments demonstrated a corticosteroid-sparing effect, with infliximab achieving the highest proportion of patients (80%) reaching ≤ 5 mg/day at 12 months (p = 0.07). Infections were more frequent with cyclophosphamide (p = 0.01), however two deadly infections occured with methotrexate.

Conclusion: Infliximab and methotrexate appear as effective and safe options for relapse prevention in neurosarcoidosis.