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

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-02-24 DOI:10.1002/ana.27218

Kundian Guo MD, Fuhua Peng MD, Jia Liu MD, Youming Long MD, Shougang Guo MD, Honghao Wang MD, Gang Yu MD, Yanlin Zhang MD, Xiong Han MD, Ewen Tu MD, Yake Zheng MD, Jialu Huang MD, Yanxia Zhou MD, Dongmei An MD, Guanyan Lin MD, Baojie Wang MD, Yuanyuan Wang MD, Ping Yang MD, Yu Jiang MD, Beijia Cui MD, Zhenyu Yang MD, Maiqi Du MD, Meiling Jiang MD, Limin Qin MD, Xueying Kong MD, Xue Gong MD, Xu Liu MD, Linjun Cai MD, Jinmei Li MD, PhD, Dong Zhou MD, PhD, Zhen Hong MD, PhD

{"title":"Efficacy and Safety of Ofatumumab Treatment for Anti-NMDA Receptor Autoimmune Encephalitis (OFF-AE): A Prospective, Multicenter Cohort Study","authors":"Kundian Guo MD, Fuhua Peng MD, Jia Liu MD, Youming Long MD, Shougang Guo MD, Honghao Wang MD, Gang Yu MD, Yanlin Zhang MD, Xiong Han MD, Ewen Tu MD, Yake Zheng MD, Jialu Huang MD, Yanxia Zhou MD, Dongmei An MD, Guanyan Lin MD, Baojie Wang MD, Yuanyuan Wang MD, Ping Yang MD, Yu Jiang MD, Beijia Cui MD, Zhenyu Yang MD, Maiqi Du MD, Meiling Jiang MD, Limin Qin MD, Xueying Kong MD, Xue Gong MD, Xu Liu MD, Linjun Cai MD, Jinmei Li MD, PhD, Dong Zhou MD, PhD, Zhen Hong MD, PhD","doi":"10.1002/ana.27218","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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; <i>p</i> = 0.026). No serious adverse events associated with ofatumumab treatment were reported.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>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</p>\n </section>\n </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"80-92"},"PeriodicalIF":8.1000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ana.27218","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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

查看原文本刊更多论文

Ofatumumab治疗抗nmda受体自身免疫性脑炎（OFF-AE）的疗效和安全性：一项前瞻性、多中心队列研究

目的：Ofatumumab为目前难治性抗n -甲基- d-天冬氨酸受体自身免疫性脑炎（nmda - ae）的二线免疫治疗提供了一种潜在的有希望的替代方案。我们旨在评估ofatumumab作为nmda - ae的新型二线免疫疗法的有效性和安全性。方法：这项前瞻性、多中心、嵌套队列研究比较了2011年10月至2024年2月在中国自身免疫性脑炎结局研究登记处（CHASE）招募的nmda - ae患者，接受和不接受ofatumumab治疗。主要转归为末次随访时达到良好功能转归的比例（改良Rankin量表[mRS]评分≤2）。次要结局包括第一个24个月随访期间mRS评分和自身免疫性脑炎临床评估量表（CASE）评分，以及ofatumumab启动后mRS评分进一步改善的比例。进行倾向评分匹配以平衡主要混杂因素。结果：共筛选AE患者715例。分析ofatumumab组和非ofatumumab组各58例倾向评分匹配的nmda - ae患者。ofatumumab组中54例（93.1%）患者在ofatumumab开始治疗后的中位14天内实现了mRS评分的进一步改善，53例（91.4%）患者在最后一次随访时达到了良好的功能结局。对于那些一线免疫治疗失败的患者，与非奥图单抗组相比，奥图单抗组在最后一次随访中表现出更快的mRS评分和CASE评分改善，并且更频繁地达到良好的功能结局(87.9% vs. 64.7%，优势比[OR] 3.95；95%置信区间[CI] 1.12-13.94；p = 0.026)。没有与ofatumumab治疗相关的严重不良事件的报道。解释：Ofatumumab显示出显著的有效性和安全性，特别是在一线免疫治疗失败的患者中，值得在nmda - ae治疗中考虑使用它。Ann neurol 2025。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.