Ofatumumab Therapy and Long‐Term Seizure Outcomes of Patients With Relapsing Anti‐ NMDA Receptor Encephalitis

OBJECTIVE: There is a lack of studies on seizure outcomes associated with ofatumumab therapy in patients for relapsing anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. We aimed to evaluate long-term seizure outcomes of ofatumumab therapy for relapsing anti-NMDA receptor encephalitis. METHODS: This is a prospective cohort study, Compared patients with relapsing anti-NMDA receptor encephalitis who had received at least 1 ofatumumab dose and a control cohort of non-ofatumumab-treated patients, continuous follow-up for 24 months. The primary outcome was the seizure outcomes (including both seizure reduction and seizure freedom; seizure reduction is defined as a reduction in seizure frequency to 50% or more of the baseline level, seizure freedom is defined as having no seizures) at the follow-up. The secondary outcomes included modified Rankin Scale (mRS) scores and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores over the 24-month follow-up. RESULTS: We enrolled 93 patients with relapsing anti-NMDA receptor encephalitis. A total of 76 patients met the requirements after the inclusion and exclusion criteria. The 38 patients received ofatumumab therapy, and the other 38 patients received non-ofatumumab therapy. Follow-up after 6 months, the ofatumumab therapy group demonstrated favorable seizure outcomes (63.16% vs. 36.84%, p < 0.05). Follow-up after 12 months, this improvement of seizure outcomes was more pronounced (78.95% vs. 60.53%, p < 0.05). Follow-up after 24 months, this difference between the two groups widened further (94.74% vs. 78.95%, p < 0.05), compared with the non-ofatumumab therapy group. Follow-up after 6 months, the ofatumumab group demonstrated a faster mRS scores (2.85 ± 0.65 vs. 3.75 ± 0.55, p < 0.05) and CASE scores (11.80 ± 1.65 vs. 13.75 ± 1.55, p < 0.05). Follow-up after 12 months, the ofatumumab group demonstrated a faster mRS scores (1.68 ± 0.45 vs. 2.39 ± 0.35, p < 0.05) and CASE scores (6.75 ± 1.45 vs. 9.39 ± 1.35 p < 0.05). Follow-up after 24 months, the ofatumumab group demonstrated a faster mRS scores (1.25 ± 0.35 vs. 1.68 ± 0.45, p < 0.05) and CASE scores (4.25 ± 0.75 vs. 6.68 ± 1.35, p < 0.05). And no serious adverse events associated with ofatumumab treatment were reported. Furthermore, Multivariate logistic regression analysis identified that early initiation of ofatumumab therapy, psychiatric symptoms, and abnormal brain MRI findings may be associated with seizure outcomes. CONCLUSIONS: Ofatumumab showed substantial improvement in long-term seizure outcomes in patients with relapsing anti-NMDA receptor encephalitis, particularly those presenting with seizures as a predominant clinical feature.