Efficacy and Safety of Ofatumumab Treatment for Anti-NMDA Receptor Autoimmune Encephalitis (OFF-AE): A Prospective, Multicenter Cohort Study.

Objective

Ofatumumab presents a potentially promising alternative to current second-line immunotherapy for refractory anti-N-methyl-D-aspartate receptor autoimmune encephalitis (NMDAR-AE). We aimed to evaluate the efficacy and safety of ofatumumab as a novel second-line immunotherapy for NMDAR-AE.

Methods

This prospective, multicenter, nested cohort study compared patients with NMDAR-AE from the CHina Autoimmune encephalitiS outcomE study registry (CHASE) recruited between October 2011 and February 2024, treated with and without ofatumumab. The primary outcome was the proportion reaching a favorable functional outcome (modified Rankin Scale [mRS] score ≤2) at the last follow-up. Secondary outcomes included mRS scores and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores over the first 24-month follow-up and the proportion with further mRS score improvement after ofatumumab initiation. A propensity score matching was performed to balance major confounders.

Results

A total of 715 patients with AE were screened. Fifty-eight propensity score-matched patients with NMDAR-AE each in the ofatumumab group and non-ofatumumab group were analyzed. Fifty-four patients (93.1%) in the ofatumumab group achieved further mRS score improvement with a median time of 14 days from ofatumumab initiation, and 53 (91.4%) reached a favorable functional outcome at the last follow-up. For those who failed first-line immunotherapy, the ofatumumab group demonstrated a faster mRS score and CASE score improvement and more frequently reached a favorable functional outcome at the last follow-up compared with the non-ofatumumab group (87.9% vs. 64.7%, odds ratio [OR] 3.95; 95% confidence interval [CI] 1.12-13.94; p = 0.026). No serious adverse events associated with ofatumumab treatment were reported.

Interpretation

Ofatumumab showed substantial efficacy and safety, particularly in patients who failed first-line immunotherapy, warranting its consideration in NMDAR-AE management. ANN NEUROL 2025;98:80-92.

References:

• Dalmau J, Graus F. Autoimmune Encephalitis‐Misdiagnosis, Misconceptions, and How to Avoid Them. JAMA Neurol 2023;80:12–14.
• Dalmau J, Tüzün E, Wu HY, et al. Paraneoplastic anti‐Nmethyl‐D‐aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61:25–36.
• Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long‐term outcome in patients with anti‐NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12:157–165.
• Nosadini M, Eyre M, Molteni E, et al. Use and safety of immunotherapeutic management of N‐Methyl‐d‐Aspartate receptor antibody encephalitis: a meta‐analysis. JAMA Neurol 2021;78:1333–1344.
• Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.