机构：[1]Department of Neurology and Institute of Neurology, West China Hospital of Sichuan University, Chengdu, China四川大学华西医院[2]Institute of Brain Science and Brain-Inspired Technology of West China Hospital, Sichuan University, Chengdu, China[3]Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China中山大学附属第三医院[4]Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China[5]Department of Neurology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China[6]Department of Neurology, Guangzhou First People’s Hospital, Guangzhou Municipal Research Institute of Clinical Medicine, Guangzhou, China[7]Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China重庆医科大学附属第一医院[8]Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China苏州大学附属第二医院[9]Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, China[10]Department of Neurology, Brain Hospital of Hunan Province, Changsha, China[11]Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China[12]Department of Neurology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China[13]Department of Neurology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China深圳市第二人民医院深圳市康宁医院深圳医学信息中心[14]Department of Neurology, West China Tianfu Hospital, Chengdu, China[15]Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, China
ObjectiveOfatumumab 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.MethodsThis 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.ResultsA 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.InterpretationOfatumumab showed substantial efficacy and safety, particularly in patients who failed first-line immunotherapy, warranting its consideration in NMDAR-AE management. ANN NEUROL 2025
基金：
National Key Research and Development Program of China [2022YFC2503800, 2022YFC2503806]; National Key R&D Program of China [82471388, 82071265]; National Science Foundation of China [2024YFHZ0056]; Sichuan Science and Technology Program [2022HXFH022]; Clinical Research Incubation Program, West China Hospital, Sichuan University [2023A03J0205]; Guangzhou Science and Technology Planning Project [2022A1515111172]; Guangdong Basic and Applied Basic Research Foundation [A2022129]; Guangdong Medical Research Foundation [2023A1515010225]; Guangdong Natural Science Foundation
第一作者机构：[1]Department of Neurology and Institute of Neurology, West China Hospital of Sichuan University, Chengdu, China[2]Institute of Brain Science and Brain-Inspired Technology of West China Hospital, Sichuan University, Chengdu, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurology and Institute of Neurology, West China Hospital of Sichuan University, Chengdu, China[2]Institute of Brain Science and Brain-Inspired Technology of West China Hospital, Sichuan University, Chengdu, China[15]Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, China
推荐引用方式(GB/T 7714)：
Guo Kundian,Peng Fuhua,Liu Jia,et al.Efficacy and Safety of Ofatumumab Treatment for Anti-NMDA Receptor Autoimmune Encephalitis (OFF-AE): A Prospective, Multicenter Cohort Study[J].ANNALS OF NEUROLOGY.2025,98(1):80-92.doi:10.1002/ana.27218.
APA：
Guo, Kundian,Peng, Fuhua,Liu, Jia,Long, Youming,Guo, Shougang...&Hong, Zhen.(2025).Efficacy and Safety of Ofatumumab Treatment for Anti-NMDA Receptor Autoimmune Encephalitis (OFF-AE): A Prospective, Multicenter Cohort Study.ANNALS OF NEUROLOGY,98,(1)
MLA：
Guo, Kundian,et al."Efficacy and Safety of Ofatumumab Treatment for Anti-NMDA Receptor Autoimmune Encephalitis (OFF-AE): A Prospective, Multicenter Cohort Study".ANNALS OF NEUROLOGY 98..1(2025):80-92
医学