A Systematic Review and Meta-Analysis of the Recurrence of Autoimmune Encephalitis

Autoimmune encephalitis (AE) is a disease with a potential for recurrence, and patients receive immunotherapy to prevent it. However, there is no consensus on the duration of immunotherapy. This study aimed to determine the recurrence rate and identify the risk factors for AE to provide guidance on the duration of immunotherapy.

A comprehensive search of the Embase, Web of Science, Cochrane, and PubMed databases was conducted from database inception until January 18, 2025, to identify clinical studies and observational studies reporting the recurrence of AE. Data on recurrence rates across different AE subtypes, age groups, treatments, and follow-up durations were aggregated. A generalized linear model was employed for regression and multivariate regression analyses.

Of the 7892 publications initially identified, 39 observational studies were ultimately included. The overall recurrence rate of AE was 0.162 (95% CI, 0.121-0.207). The recurrence rate for anti-NMDAR encephalitis was 0.148 (95% CI, 0.108-0.193) and significantly decreased after teratoma removal. Second-line treatment decreased the AE recurrence rate. Multivariate regression analysis indicated that having anti-LGI1 encephalitis, age, and shorter delayed treatment duration were risk factors for recurrence. After 1 year of follow-up, the recurrence rate did not increase.

Based on the findings, we recommend proactive second-line immunotherapy for patients with AE to reduce recurrence rates, particularly for those with anti-LGI1 encephalitis and adult individuals. Immunotherapy maintenance over 1 year may not be required.