Nabil Seery, Robb Wesselingh, Paul Beech, Laurie McLaughlin, Tiffany Rushen, Amy J Halliday, Liora Ter Horst, Sarah P Griffith, Mirasol Forcadela, Tracie H Tan, Christina Kazzi, Cassie Nesbitt, James Broadley, Katherine Buzzard, Andrew Duncan, Wendyl J D'Souza, Yang Tran, Anneke Van Der Walt, Genevieve Skinner, Bruce V Taylor, Andrew Swayne, Amy Brodtmann, David Gillis, Ernest Gerard Butler, Tomas Kalincik, Udaya K Seneviratne, Richard A Macdonell, Stefan Blum, Sudarshini Ramanathan, Charles B Malpas, Stephen W Reddel, Todd A Hardy, Terence J O'Brien, Paul G Sanfilippo, Helmut Butzkueven, Mastura Monif
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引用次数: 0
Abstract
Background and objectives: 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.
Methods: 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.
Results: A single course of rituximab was associated with longer time to first relapse (hazard ratio [HR] 0.11, 95% CI 0.02-0.70, p = 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, p = 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, p = 0.47).
Discussion: 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.
Classification of evidence: This study provides Class IV evidence that rituximab delays relapses in patients with anti-NMDAR antibody-mediated encephalitis.
背景和目的：利妥昔单抗是一种抗cd20单克隆抗体，用于抗nmdar抗体（Ab）介导的脑炎患者，作为急性升级治疗和长期复发风险降低治疗。急性期单疗程治疗对未来复发风险的潜在长期益处尚不确定。此外，减少复发风险的最佳给药时间尚不清楚。本研究的目的是评估单疗程利妥昔单抗对复发率的影响。我们还研究了一个疗程的利妥昔单抗在抗nmdar抗体介导的脑炎成人患者中的作用持续时间。方法：我们从澳大利亚10家医院招募了67例抗nmdar抗体介导的脑炎患者。在Cox比例风险模型中，利妥昔单抗暴露被量化为时变协变量。结果：单疗程的利妥昔单抗与较长的首次复发时间相关（风险比[HR] 0.11, 95% CI 0.02-0.70, p = 0.02）。对于考虑重新给药的患者，在调整了同时免疫治疗和发病时卵巢畸胎瘤的存在后，利妥昔单抗与最后一次输注后6个月首次复发的时间较长相关（HR 0.05, 95% CI 0.00-0.48, p = 0.005）。疗程结束后，治疗效果未持续到12个月（HR 0.60, 95% CI 0.15-2.44, p = 0.47）。讨论：单疗程的利妥昔单抗可降低抗nmdar抗体介导的脑炎复发的风险。在考虑重新给药的选定患者中，6个月给药可延迟复发。证据分类：本研究提供了IV级证据，证明利妥昔单抗延缓抗nmdar抗体介导的脑炎患者的复发。
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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