Efficacy and safety of rituximab in myelin oligodendrocyte glycoprotein antibody-associated disorders compared with neuromyelitis optica spectrum disorder: a systematic review and meta-analysis

Abstract

BackgroundRituximab (RTX) efficacy in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGADs) is still poorly understood, though it appears to be lower than in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSDs). The aim of this systematic review and meta-analysis is to assess the efficacy and safety profile of RTX in patients with MOGAD and to compare RTX efficacy between MOGAD and AQP4-IgG+NMOSD.MethodsWe searched original English-language articles published between 2012 and 2021 in MEDLINE, Cochrane, Central Register of Controlled Trials and clinicaltrials.gov, reporting data on RTX efficacy in patients with MOGAD. The main outcome measures were annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score mean differences (MDs) after RTX. The meta-analysis was performed with a random effects model. Covariates associated with the outcome measures were analysed with a linear meta-regression.ResultsThe systematic review included 315 patients (138 women, mean onset age 26.8 years) from 32 studies. Nineteen studies (282 patients) were included in the meta-analysis. After RTX, a significant decrease of ARR was found (MD: −0.92, 95% CI –1.24 to –0.60, p<0.001), markedly different from the AQP4-IgG+NMOSD (MD: −1.73 vs MOGAD −0.92, subgroup difference testing: Q=9.09, p=0.002). However, when controlling for the mean ARR pre-RTX, this difference was not significant. After RTX, the EDSS score decreased significantly (MD: −0.84, 95% CI −1.41 to –0.26, p=0.004). The frequency of RTX-related adverse events was 18.8% (36/192) and overall RTX-related mortality 0.5% (1/192).ConclusionsRTX showed effective in MOGAD, although to a lesser extent than in AQP4-IgG+NMOSD, while the safety profile warrants some caution in its prescription. Randomised-controlled trials are needed to confirm these findings and provide robust evidence to improve treatment strategies in patients with MOGAD.PROSPERO registration numberCRD42020175439.

MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity

“…Thus, we investigated whether clinical characteristics, particularly treatment status, MOG-IgG magnitude, and days from relapse correlated with induction of effector functions. While several retrospective observational studies have reported the annual relapse rate to be reduced in MOGAD patients treated with rituximab or even more so with intravenous immunoglobulin (50)(51)(52)(53)(54)(55)(56), for unclear reasons, rituximab appears to be less effective at preventing attacks in MOGAD than NMOSD (57). Indeed, our cohort does not show a difference in autoantibody-mediated effector functions in relation to treatment, and more strikingly, while we found correlations between MOG-IgG binding and effector function, and effector function and days from relapse, we did not find a correlation between MOG-IgG binding and days from relapse.…”

MOG antibody-associated optic neuritis

“…In a prospective study, a significant proportion of MOGAD relapses on rituximab treatment occurred despite effective B-cell depletion compared to AQP4-IgG positive NMOSD relapses, implicating less biological efficacy in MOGAD [151]. A meta-analysis of nineteen studies found a significantly greater reduction in annualised relapse rates post-rituximab in AQP4-IgG positive NMOSD compared to MOGAD [152].…”

Oral corticosteroid dosage and taper duration at onset in myelin oligodendrocyte glycoprotein antibody-associated disease influences time to first relapse

“…At present, there is equipoise regarding optimal therapeutic approaches in MOGAD, with variable clinician preference and experience. 16 While retrospective studies and systematic reviews report intravenous immunoglobulin and rituximab may reduce activity in relapsing MOGAD, [17][18][19] there is currently no consensus on optimal treatment at onset. Our objective was to explore potential therapeutic strategies for MOGAD patients at disease onset in a retrospective cohort, by evaluating whether a specific oral prednisone regimen could effectively delay time to first relapse (TTFR), while minimising cumulative corticosteroid exposure.…”