Prior observational studies for autoimmune encephalitis (AE) have mostly focused on outcomes after acute immunotherapies with better outcomes associated with earlier immunotherapy use. However, the impact of long-term immunotherapy and its association with clinical relapse is not well known.

We conducted a retrospective study of consecutive patients meeting published clinical criteria for AE evaluated at UC San Diego and Rady Children's Hospital from January 2007 to November 2021. Survival analysis and Cox multivariable regression models were used to evaluate relapse risk using rituximab exposure as a time-dependent variable. Pooled and age-stratified analyses were performed.

A total of 204 pediatric and 380 adult participants were screened of which 30 pediatric and 75 adult participants were included. The most common antibody subtype in both cohorts was anti-NMDA receptor (76% in pediatric, 34% in adult). Relapses occurred in 31% of pediatric antibody-positive, 40% of adult antibody-positive, and 20% of adult antibody-negative cases. Times to first relapse (TTFR) were 10.6 ± 7.4 months (pediatric antibody-positive), 13.1 ± 24.5 months (adult antibody-positive), and 6.9 ± 3.8 months (adult antibody-negative). Rituximab was the most common second-line immunotherapy used. Combining pediatric and adult data, rituximab use was associated with a 71% lower hazard for time to first relapse (hazard ratio [HR] 0.29, 95% CI 0.09–0.85) and 51% lower hazard for recurring relapses (HR 0.49, 95% CI 0.9–1.26). The HR for TTFR with rituximab use in children was 0.30 (95% CI 0.05–1.69), 0.29 (95% CI 0.07–1.29) in adults, 0.32 in non-NMDA antibody-positive encephalitis (95% CI 0.07–1.39), and 0.42 (95% CI 0.07–2.67) for anti-NMDAR.

Relapses are common in pediatric and adult patients with AE, although less frequently in anti-NMDARE. Using a rigorous survival model, we demonstrate a substantial benefit of rituximab use for reducing relapse rates in AE, especially for the adult population.

This study provides Class IV evidence that rituximab is associated with a lower hazard to relapse in patients with AE.

先前针对自身免疫性脑炎（AE）的观察性研究主要集中于急性免疫治疗后的结果，早期免疫治疗的使用效果更好。然而，长期免疫治疗的影响及其与临床复发的关系尚不清楚。

我们对 2007 年 1 月至 2021 年 11 月在加州大学圣地亚哥分校和 Rady 儿童医院评估的符合已发布 AE 临床标准的连续患者进行了回顾性研究。生存分析和 Cox 多变量回归模型用于评估复发风险，使用利妥昔单抗暴露作为时间-因变量。进行了汇总分析和年龄分层分析。

总共筛选了 204 名儿童和 380 名成人参与者，其中包括 30 名儿童和 75 名成人参与者。两个队列中最常见的抗体亚型是抗 NMDA 受体（儿童中 76%，成人中 34%）。儿童抗体阳性病例中有 31% 出现复发，成人抗体阳性病例中有 40% 出现复发，成人抗体阴性病例中有 20% 出现复发。首次复发时间 (TTFR) 分别为 10.6 ± 7.4 个月（儿童抗体阳性）、13.1 ± 24.5 个月（成人抗体阳性）和 6.9 ± 3.8 个月（成人抗体阴性）。利妥昔单抗是最常用的二线免疫疗法。结合儿科和成人数据，使用利妥昔单抗可使首次复发时间风险降低 71%（风险比 [HR] 0.29，95% CI 0.09–0.85），使复发风险降低 51%（HR 0.49，95%）。 CI 0.9–1.26）。儿童使用利妥昔单抗的 TTFR 的 HR 为 0.30 (95% CI 0.05–1.69)，成人为 0.29 (95% CI 0.07–1.29)，非 NMDA 抗体阳性脑炎为 0.32 (95% CI 0.07–1.39)，抗 NMDAR 为 0.42 (95% CI 0.07–2.67)。

复发在儿童和成人 AE 患者中很常见，但在抗 NMDARE 患者中复发率较低。使用严格的生存模型，我们证明了使用利妥昔单抗对于降低 AE 复发率有显着益处，特别是对于成年人群。

这项研究提供了 IV 类证据，表明利妥昔单抗与 AE 患者复发风险较低相关。