Ofatumumab Outperforms Rituximab in Reducing Relapse Risk of MOGAD, Study Shows

A newly published single-center observational study in China showed that ofatumumab (Kesimpta; Novartis) treatment was associated with significant reductions in annualized relapse rate (ARR) compared with off-label rituximab in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). In addition to demonstrating a favorable safety profile, these findings suggest that ofatumumab may be associated with greater relapse reduction compared with rituximab in patients with MOGAD.¹

Before initiating treatment, patients who received ofatumumab (n = 22) had a median of 2 relapses and an ARR of 1.30 (95% CI, 0.74-2.29). Over a median treatment duration of 19.5 months, 4 patients (18.18%) experienced relapse, with ARR decreasing to 0.12 (95% CI, 0.04-0.35), corresponding to an incidence rate ratio (IRR) of 10.86 (95% CI, 3.22-36.70; P <.001). In the rituximab group (n = 21), patients had a median of 2 relapses before treatment initiation and an ARR of 1.34 (95% CI, 0.73-2.48). During a median treatment duration of 18 months, 12 patients (57.14%) relapsed, and ARR decreased to 0.55 (95% CI, 0.28-1.06), yielding an IRR of 2.46 (95% CI, 1.00-6.06; P = .050).

“Although rituximab is commonly used off–label for treating MOGAD, largely due to its proven success in NMOSD, emerging real–world data highlight its limited efficacy in MOGAD. A growing body of retrospective studies indicates that despite effective B–cell depletion, many MOGAD patients undergoing [rituximab] therapy experience high relapse rates,” senior author Chao Quan, MD, professor in the Department of Neurology and Huashan Rare Disease Center, Huashan Hospital and Shanghai Medical College, Fudan University, and colleagues wrote. “This discrepancy in clinical outcomes may reflect the distinct immunopathogenesis of MOGAD, which appears to involve a complex interplay of immune mechanisms.”

In this study, investigators evaluated the efficacy and safety of ofatumumab in patients with diagnosed with MOGAD,² and compared outcomes with rituximab. The analysis included patients treated with ofatumumab and those treated with rituximab between February 2016 and September 2025.

Ofatumumab was administered subcutaneously at 20 mg on days 1, 7, and 14, followed by 20 mg every 4 weeks beginning on day 28. Rituximab was administered intravenously at 500 mg on days 1 and 2, followed by 500-mg maintenance doses every 6 months. The primary outcome was relapse, assessed by ARR and time to relapse, with secondary outcomes that included disability status, measured by Expanded Disability Status Scale (EDSS) score, and adverse events (AEs).

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After propensity score matching, investigators compared relapse outcomes between the ofatumumab and rituximab groups. In the ofatumumab cohort (n = 11), 72.73% of patients remained relapse-free, with a median of 0 relapses during treatment, an ARR of 0.18 (95% CI, 0.05-0.64), and a median time to first relapse of 7 months following treatment initiation. In comparison, 27.28% of patients in the rituximab group (n = 11) remained relapse-free during a comparable treatment duration (P = .088).

Across the total cohort, the interval between the most recent attack and treatment initiation was comparable between the ofatumumab and rituximab groups (P = .111). In patients treated with ofatumumab, EDSS scores significantly decreased from a median of 1.0 before treatment to 0 at the last follow-up (P = .008). By comparison, patients treated with rituximab showed no significant change in EDSS scores, with median scores remaining at 1.0 from baseline to the last follow-up (P = .359). Following propensity score matching, EDSS scores were comparable between the 2 treatment groups both before treatment initiation (P = .606) and at the last follow-up (P = .562).

After propensity score matching, 6 of 11 patients (54.55%) treated with ofatumumab experienced a total of 8 AEs, with fever and upper respiratory infection reported most frequently. Additional AEs included pruritus, generalized pain, urinary tract infection, and elevated blood glucose levels, each occurring in 1 of 8 events (12.50%). In the rituximab group, 5 of 11 patients (45.45%) experienced 14 total AEs, most commonly upper respiratory tract infection, followed by pruritus, hair loss, and elevated blood lipid levels. Infection-related AEs were reported in 37.5% of patients receiving ofatumumab and 50.0% of those receiving rituximab. Investigators also reported 1 serious infection event of pneumonia in a pediatric patient.

“Due to the high–dose pulse administration of rituximab, an end–of–dose effect may occur, with B cell reappearance observed near the end of 6 month dosing interval. As we observed, a significant proportion of MOGAD relapses in the [rituximab] group occurred during the 5–6 month period following a dose, whereas patients on ofatumumab maintained lower B–cell percentages even at relapse than the rituximab-treated patients,” Quan et al noted.¹ “Collectively, these factors may explain the variable efficacy of [rituximab] in MOGAD and underscore the need for alternative therapeutic strategies to improve clinical outcomes.”

REFERENCES
1. Fan Y, Zhou L, ZhangBao J, Tan H, Wang Z, Quan C. Ofatumumab in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Comparison With Rituximab. Ann Clin Transl Neurol. Published online April 26, 2026. doi:10.1002/acn3.70392
2. Banwell B, Bennett JL, Marignier R, et al. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol. 2023;22(3):268-282. doi:10.1016/S1474-4422(22)00431-8