Seery Nabil, Wesselingh Robb, Beech Paul, McLaughlin Laurie, Rushen Tiffany, Halliday Amy J, Ter Horst Liora, Griffith Sarah P, Forcadela Mirasol, Tan Tracie H, Kazzi Christina, Nesbitt Cassie, Broadley James, Buzzard Katherine, Duncan Andrew, D'Souza Wendyl J, Tran Yang, Van Der Walt Anneke, Skinner Genevieve, Taylor Bruce V, Swayne Andrew, Brodtmann Amy, Gillis David, Butler Ernest Gerard, Kalincik Tomas, Seneviratne Udaya K, Macdonell Richard A, Blum Stefan, Ramanathan Sudarshini, Malpas Charles B, Reddel Stephen W, Hardy Todd A, O'Brien Terence J, Sanfilippo Paul G, Butzkueven Helmut, Monif Mastura
Department of Neuroscience, Monash University, Melbourne, Australia.
Department of Neurology, Alfred Health, Melbourne, Australia.
Neurol Neuroimmunol Neuroinflamm. 2025 Jul;12(4):e200395. doi: 10.1212/NXI.0000000000200395. Epub 2025 May 30.
Rituximab is an anti-CD20 monoclonal antibody used in patients with anti-NMDAR antibody (Ab)-mediated encephalitis as both an acute escalation therapy and a longer term relapse risk-reduction treatment. The potential long-term benefit of a single course administered during the acute disease phase on future relapse risk is uncertain. Moreover, the optimal dosing duration to reduce relapse risk is unknown. The aim of this study was to evaluate the effect of a single course of rituximab on relapse incidence. We also studied the duration of effect of a course of rituximab in adult patients with anti-NMDAR Ab-mediated encephalitis.
We recruited 67 patients with anti-NMDAR Ab-mediated encephalitis from 10 Australian hospitals. Rituximab exposure was quantified as a time-varying covariate in Cox proportional hazard models.
A single course of rituximab was associated with longer time to first relapse (hazard ratio [HR] 0.11, 95% CI 0.02-0.70, = 0.02). For patients in whom redosing is considered, rituximab was associated with longer time to first relapse at 6 months after the last infusion, after adjusting for concurrent immunotherapies and the presence of ovarian teratoma at disease onset (HR 0.05, 95% CI 0.00-0.48, = 0.005). The treatment effect did not persist out to 12 months after a given course (HR 0.60, 95% CI 0.15-2.44, = 0.47).
A single course of rituximab reduces the risk of relapse of anti-NMDAR antibody-mediated encephalitis. In select patients for whom redosing of rituximab is considered, administration at 6 months delays relapses.
This study provides Class IV evidence that rituximab delays relapses in patients with anti-NMDAR antibody-mediated encephalitis.
利妥昔单抗是一种抗CD20单克隆抗体，用于抗N-甲基-D-天冬氨酸受体（NMDAR）抗体介导的脑炎患者，作为急性强化治疗和降低长期复发风险的治疗手段。在急性疾病阶段给予一个疗程的利妥昔单抗对未来复发风险的潜在长期益处尚不确定。此外，降低复发风险的最佳给药持续时间也未知。本研究的目的是评估一个疗程的利妥昔单抗对复发率的影响。我们还研究了利妥昔单抗疗程对成年抗NMDAR抗体介导的脑炎患者的疗效持续时间。
我们从10家澳大利亚医院招募了67例抗NMDAR抗体介导的脑炎患者。在Cox比例风险模型中，将利妥昔单抗暴露量作为一个随时间变化的协变量进行量化。
一个疗程的利妥昔单抗与首次复发时间延长相关（风险比[HR]0.11，95%置信区间0.02 - 0.70，P = 0.02）。对于考虑再次给药的患者，在调整了同时进行的免疫治疗和疾病发作时卵巢畸胎瘤的存在情况后，利妥昔单抗与最后一次输注后6个月的首次复发时间延长相关（HR 0.05，95%置信区间0.00 - 0.48，P = 0.005）。在给定疗程后，治疗效果在12个月时未持续存在（HR 0.60，95%置信区间0.15 - 2.44）。
一个疗程的利妥昔单抗可降低抗NMDAR抗体介导的脑炎的复发风险。在考虑再次给药的特定患者中，6个月时给药可延迟复发。
本研究提供了IV级证据，表明利妥昔单抗可延迟抗NMDAR抗体介导的脑炎患者的复发。
