Anti-IL-6 Therapies for Neuromyelitis Optica Spectrum Disorders: A Systematic Review of Safety and Efficacy

Abstract

Background: Neuromyelitis Optica Spectrum Disorder (NMOSD) is a chronic autoimmune disease of the central nervous system that causes recurrent attacks of optic neuritis, myelitis, and brainstem symptoms, resulting in severe neurological disability. Preventive treatment with immunosuppressive agents reduces relapse rate and improves long-term prognosis. In recent years, the potential therapeutical effect of new agents have been investigated. Two of these, the antiinterleukin 6 (IL-6) agents tocilizumab and satralizumab, have been studied in active NMOSD. Objective: To systematically review the current data regarding the efficacy and safety of anti-IL-6 agents in NMOSD. Result: Fourteen case reports and 5 case series of intravenous tocilizumab have shown beneficial clinical and paraclinical effects compared to commonly used therapies, and another case series of subcutaneous tocilizumab has shown it is as effective as the IV formulation. A phase 2 comparative trial has shown tocilizumab IV to be more effective than azathioprine for relapse prevention. A phase 3 trial ofsubcutaneoussatralizumab versus placebo, hasshown a lower risk of relapse in the sartralizumabtreated group, both as add-on therapy to stable immunosuppressant and as monotherapy. Tocilizumab also reduced pain severity in two trials and fatigue scores in one trial, but satralizumab did not significantly improve pain and fatigue. Adverse events with both agents were relatively mild and comparable to placebo and azathioprine. Conclusions: The anti-Il-6 agents tocilizumab and satralizumab show promising results in active NMOSD. Further randomized, larger-scale trials are needed to better define the role of these agents in the growing arsenal of NMOSD treatments.

New progress in the treatment of neuromyelitis optica spectrum disorder with monoclonal antibodies (Review)

“…There were no deaths or anaphylactic reactions in either trials. A systematic review showed that the anti-IL-6 drugs TCZ and SA237 had good efficacy and safety in NMOSD (42). Nevertheless, a long course of treatment and long-term monitoring are still needed to assess the real risks of infection, neutropenia and cardiovascular side effects associated with these drugs (43).…”

What's new in neuromyelitis optica spectrum disorder treatment?

“…Several retrospective studies showed the efficacy and safety of Tocilizumab in NMOSD. [ 74 ] Tocilizumab was compared with azathioprine in a head-to-head prospective, randomized open label phase II study (TANGO trial) in NMOSD. [ 75 ] Both groups had 59 patients with 85% and 90% AQP4-IgG + , respectively.…”

Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder

“…IL-6 levels are elevated in blood and cerebrospinal fluid of NMOSD patients and correlate with AQP4-IgG levels and disease severity [ 72 , 73 ]. IL-6 facilitates disruption of the blood–brain barrier and enhances lesion severity [ 74 , 75 ], and promotes AQP4-IgG production in vitro and ex vivo [ 76 ].…”