Do Anti-IL-6 Receptor Blockers Hold Promise for Relapse Prevention in MOGAD?

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) 1 is a rare autoimmune demyelinating disease of the CNS in which up to half of patients have a relapsing course, with the remainder having a monophasic course. 1 Disability tends to accumulate after each attack, and rarely, life-threatening attacks can occur, highlighting the need for effective attack-prevention treatments. 1 There are currently no proven attack-prevention treatments in MOGAD, although multiple prospective randomized placebo-controlled clinical trials are underway.While awaiting class I evidence to guide us, the choice of attack-prevention treatment in relapsing MOGAD has to rely on retrospective data.Several immunosuppressive therapies including intravenous immunoglobulin (IVIg), rituximab, azathioprine, and mycophenolate mofetil have shown potential in reducing relapse rates in retrospective analyses, but data suggest that rituximab may be less effective in MOGAD than in neuromyelitis optica spectrum disorder (NMOSD). 2 IVIg has shown potential utility, yet the cost and global shortage limit its use. 2 Therefore, there remains an unmet need for broader, more effective therapeutic options in MOGAD while we await class I data.Recent efforts have focused on the interleukin-6 (IL-6) pathway. 3,4IL-6 is a pleiotropic cytokine that drives acute inflammation and increases endothelial permeability, such as disrupting the blood-brain barrier and promoting immune cell trafficking into the CNS.It enhances T-cell differentiation, supports B-cell growth and plasma cell maturation, and promotes IgG production-mechanisms potentially amplifying myelin oligodendrocyte glycoprotein antibody (MOG-IgG) synthesis. 3Although not disease-specific, IL-6 dysregulation contributes to autoimmunity and is elevated in MOGAD in both serum and CSF. 3 Levels are generally higher than in multiple sclerosis and rise further during acute attacks, where higher concentrations are associated with worse outcomes. 3oreover, the clinical success of IL-6 pathway blockade in disorders such as rheumatoid arthritis, giant cell arteritis, and AQP4-IgG-positive NMOSD underscores its therapeutic potential.Collectively, these observations position IL-6 inhibition as a potential attack-prevention strategy for MOGAD.To date, small observational series suggest that off-label tocilizumab, a widely used IL-6 receptor blocker, reduces relapse rates, 4-6 and a meta-analysis suggested that tocilizumab may have the lowest relapse rates among the aforementioned treatment options in MOGAD.Clinical trials are underway for tocilizumab and satralizumab. 7,8In this context, in this issue of Neurology : Open Access, Francesco Capecchi and Marina Herwerth, among other collabo- rators, 9 shared retrospective treatment data from the largest cohort to date.The main finding was that, after 6 months of tocilizumab treatment, relapse frequency declined substantially: only 2 of 16 patients relapsed during a median follow-up of 29.5 months (range 6-126), providing class IV of evidence that tocilizumab reduces relapse risk in MOGAD both as firstline therapy and after failure of other agents, consistent with previous studies.These data support tocilizumab as a reasonable first-line option while we await class I of evidence and further validate IL-6 as a therapeutic target.Even if such evidence favors newer agents (satralizumab, a modern IL-6R blocker monoclonal antibody), their cost may limit access in many