Interleukin-6 Blockade in Refractory Neuro-Behçet’s Disease: A Systematic Literature Review

This review aimed to assess the efficacy and safety of interleukin (IL)-6 inhibition in neuro-Behçet’s disease (NBD) refractory to standard immunosuppressive therapy. This systematic literature review was performed in accordance with the PRISMA guidelines. The PubMed, EMBASE, Cochrane, and Web of Science databases were searched for studies on the efficacy of IL-6 blockade in patients with refractory NBD. We also identified cases of NBD with recurrently elevated IL-6 levels in cerebrospinal fluid (CSF) during tumor necrosis factor (TNF) alpha therapy at our institution. We identified 11 studies including 25 patients with NBD who were treated with tocilizumab. No eligible studies of other IL-6-targeted agents were identified. Among the 24 patients evaluated for response, 22 (91.7%, 95% confidence interval [CI] 74.2–97.7%) were classified as responders. Reduction of the glucocorticoid dose was achieved in at least 75.0% (18/24, 95% CI 55.1–88.0%) of patients receiving concomitant glucocorticoid. Adverse events were infrequently reported (infusion reaction, cytopenia, infections), and one responder experienced worsening mucocutaneous inflammation. Two cases identified at our institution had recurrent neurological symptoms with high CSF IL-6 levels and an incomplete response to TNF inhibitor therapy, requiring repeated hospitalization. IL-6 blockade is a promising option for patients with refractory or recurrent NBD who have failed conventional therapies. Given the limited quality of the current evidence, prospective studies are needed to clarify the long-term efficacy and safety of IL-6-targeted therapy in NBD. UMIN000058445.