Long-term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder and MOG Antibody Disease

Abstract

Background and Objectives:Rituximab is used widely for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-IgG associated disease (MOGAD), however data regarding the effectiveness and safety of long-term rituximab use in these conditions are limited. In this study we sought to evaluate long-term clinical outcomes in patients with aquaporin-4 IgG seropositive (AQP4-IgG+) NMOSD and MOGAD treated with rituximab.Methods:We performed a retrospective chart review of patients with AQP4-IgG+ NMOSD or MOGAD followed at the Johns Hopkins Neuromyelitis Optica Clinic and included patients who had received at least one dose of rituximab.Results:We identified 111 NMOSD and 23 MOGAD patients who fulfilled inclusion criteria. Median duration of rituximab treatment for the NMOSD patients was 3.7 years (range:0.5 to 13.2) and for the MOGAD patients was 2.1 years (range:0.5 to 7.0). The annualized relapse rate (ARR) decreased after rituximab initiation in both NMOSD (median ARR:pre-treatment 1.1, post-treatment 0; p<0.001) and MOGAD (median ARR:pre-treatment 1.9, post-treatment 0.3; p=0.002). Relapses on rituximab occurred in 31 NMOSD (28%) and 14 MOGAD (61%) patients. The majority of NMOSD treatment failures (37/48 relapses; 77%) occurred either within the initial 6-months after starting rituximab (n=13 relapses) or in the setting of delayed/missed rituximab doses and/or peripheral B cell reconstitution (n=24 relapses) whereas in MOGAD, these circumstances were present in a smaller proportion of treatment failures (19/35 relapses; 54%). The risk of relapse on rituximab was greater for MOGAD compared to NMOSD patients (hazard ratio:2.8, 95%CI: 1.5 to 5.2, p=0.001). Infections requiring hospitalization occurred in 13% and IgG hypogammaglobulinemia in 17% of patients. Median rituximab treatment duration before IgG hypogammaglobulinemia onset was 5.4 years (IQR:3.8 to 7.7).Conclusions:Rituximab treatment is associated with reduced annualized relapse rate in AQP4-IgG seropositive NMOSD, especially in the absence of gaps in treatment and/or B cell reconstitution. In MOGAD, while a reduction in relapses was observed after initiation of rituximab, this association appeared to be less robust than in AQP4-IgG seropositive NMOSD. Severe infections and hypogammaglobulinemia occurred in a significant proportion of patients, highlighting the need for close monitoring of infectious complications.Classification of Evidence:This study provides Class IV evidence that rituximab decreases the annualized relapse rate in AQP4-IgG seropositive NMOSD and MOGAD.

High dimensional mass cytometry analysis unravels distinct profiles of peripheral blood mononuclear cells in patients with neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein associated disease or in health

“…Patients with MOGAD treated with rituximab experience relapses and appeared to be less robust than NMOSD despite a complete B-cell depletion. Severe infections and hypogammaglobulinemia occurred in a signi cant proportion of MOGAD patients [30]. In MOGAD, depletion of CD20 T cells by rituximab administration may lead to reduction of protective function, disease relapse and severe infections in patients.…”

Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine

“…9 Patients with MOG-IgG are frequently responsive to corticosteroids in the acute phase and less responsive to rituximab as maintenance therapy, whereas those with AQP4-IgG usually require second-line acute treatments such as plasma exchange and respond quite well to rituximab in the long term. 10 All these differences led to the recognition of MOGAD as a separate entity, culminating in the International MOGAD Panel proposed criteria in 2023. 8 Of note, unlike in MS or NMOSD, the positivity of a biomarker (MOG-IgG) is indispensable for the fulfillment of the diagnostic criteria, making this a good example of the precision medicine approach.…”

“…9 Patients with MOG-IgG are frequently responsive to corticosteroids in the acute phase and less responsive to rituximab as maintenance therapy, whereas those with AQP4-IgG usually require second-line acute treatments such as plasma exchange and respond quite well to rituximab in the long term. 10…”

Clinical and epidemiological correlates of treatment change in patients with NMOSD: insights from the CIRCLES cohort

“…Open-label studies suggest that several therapies reduce the risk of relapse in patients with NMOSD. For example, the efficacy of rituximab in reducing the annual relapse rate (ARR) has been reported in multiple studies [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Metaanalyses of such studies found that, collectively, ≈ 60% of patients were relapse-free on rituximab [24].…”

“…Metaanalyses of such studies found that, collectively, ≈ 60% of patients were relapse-free on rituximab [24]. Serious adverse events such as serious or severe infection or infusion reaction occurred in 26% of patients, raising concerns regarding rituximab as first-line therapy [23,25]. Importantly, the majority of these studies did not use the 2015 International Panel for NMOSD Diagnosis (IPND) criteria for inclusion.…”