Adalimumab for the Treatment of CNS Sarcoidosis

BackgroundIn observational analyses, infliximab, an infused chimeric antibody inhibiting tumor necrosis factor-alpha, appears to provide benefit in the treatment of CNS sarcoidosis, including in patients with refractory disease. Potential obstacles to treatment include the need for an infusion infrastructure and risk of developing neutralizing anti-drug antibodies that impair drug function. Adalimumab is an injectable humanized monoclonal antibody TNF inhibitor, but the data supporting its use in neurosarcoidosis is limited. Design/MethodsPatients with definite or probable CNS sarcoidosis treated with adalimumab were retrospectively identified. ResultsNine patients were included (median age 47.0; male 55.6%;Black 77.8%, White 11.1%, race unreported 11.1%; extra-neurologic systemic sarcoidosis 100%) and diagnostically supported by systemic (66.7%) and neurologic (33.3%) biopsies. Median follow-up duration was 26 months following initiation of adalimumab with no patients lost to follow-up while using adalimumab. The most common phenotypes were cranial leptomeningitis(66.7%), myelitis (55.6%), hypothalamic disease (33.3%), and brain parenchymal lesions (33.3%). Median pre-adalimumab disease characteristics included: neurosarcoidosis disease duration 58 months, 2 prior attacks, mRS 2, EDSS 3.5, and 2 prior immunosuppressants (including 5 treated with infliximab). Treatment details included: none using loading doses, 88.9% maintained on 40 mg every other week, 11.1% maintained on 40 mg every week; 55.6% using concomitant immunosuppression; and median adalimumab treatment duration of 6 months. Two patients (22.2%) exhibited breakthrough disease at 2 and 6 months. Five patients (55.6%) discontinued adalimumab, and relapses occurred in 2 patients 3 months after adalimumab discontinuation. ConclusionsIn this relatively small retrospective dataset, most patients (77.8%) responded favorably to adalimumab, including an arrayof CNS phenotypes, those with disease refractory to other treatments, and those with prolonged disease. There was a relapse of neurosarcoidosis in 40% of patients (2 of 5) within 3 months after stopping adalimumab.