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ABSTRACT & COMMENTARY
Rituximab to Prevent Relapse in Anti-NMDAR Antibody-Mediated Encephalitis
July 1, 2025 3 minutes read
By Hai H. Hoang, MD
Synopsis: This long-term follow-up study of 67 patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis demonstrated that initial treatment with rituximab was associated with a longer time before a relapse occurred.
Source: Seery N, Wesselingh R, Beech P, et al; Australian Autoimmune Encephalitis Consortium. Rituximab use for relapse prevention in anti-NMDAR antibody-mediated encephalitis: A multicenter cohort study. Neurol Neuroimmunol Neuroinflamm. 2025;12(4):e200395.
Although immune-mediated encephalitis syndromes are rare, N-methyl-D-aspartate receptor (NMDAR) antibody-mediated encephalitis is the most frequent antibody-mediated autoimmune encephalitis encountered in general neurology practice. This patient population is a good model to study autoimmune encephalitis diseases, lacking the larger sample sizes required for a randomized treatment trial.
The severity and duration of the first acute phase in NMDAR is variable, but less is known about the relapse rate. One of the primary drugs to reduce relapse is rituximab, an anti-CD20 monoclonal antibody. The aim of this study was to evaluate the effect of a single course of rituximab on relapse prevention and the duration of benefits before a next relapse.
This was a multicenter collaboration with 10 members in the Australian Autoimmune Encephalitis Consortium Study. Retrospective data were collected on patients with confirmed NMDA encephalitis, including demographics, antibody titers, magnetic resonance imaging (MRI) findings, cerebrospinal fluid (CSF) results, and treatment course, with an emphasis on understanding the details of rituximab administration.
A total of 67 patients were included in the analysis. The median time to rituximab administration was 58 days. Forty-nine percent of patients received rituximab during their acute admission, 7% received rituximab after discharge from the hospital because of ongoing clinical symptoms, and 13% received treatment after a relapse. Nineteen patients had at least one relapse, which occurred at a median of 764 days from initial admission. Eighteen patients required multiple courses after the first relapse.
In patients who relapsed, there was a longer time to administration of rituximab (median of 156 days vs. 35 days). Delay to first-line immunotherapy was associated with a shorter time to first relapse. A single course of rituximab increased the time to first relapse. In a multivariate analysis, the benefits of a second course of rituximab six months after the initial treatment course were associated with greater time before the first relapse. However, this effect was not seen when subsequent treatment was given 12 months or longer after the initial course of treatment.
Commentary
This study looked at long-term outcomes in patients with NMDA encephalitis, a rare disease with little known about treatment results or long-term outcomes. There are no randomized treatment trials because of the rarity of the condition. It is important to conduct long-term follow-up studies to understand the natural history and response to treatment of these conditions.
This study suggests that the administration of rituximab as initial therapy does reduce the risk of relapse, and repeat dosing at six months appears to extend that window. This effect was not seen when repeat dosing was given 12 months or later after the initial treatment. The information in this long-term follow-up study should give clinicians some confidence to support the administration of rituximab in patients with an NMDA encephalitis, with six-month interval dosing being the preferred frequency of treatment.
At the present time, we have little information regarding the efficacy of other immune-mediating therapies for the treatment of relapses in patients with NMDA encephalitis.
Hai H. Hoang, MD, is Assistant Professor of Clinical Neurology, Weill Cornell Medical College.
This long-term follow-up study of 67 patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis demonstrated that initial treatment with rituximab was associated with a longer time before a relapse occurred.
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