An updated, comprehensive meta-analysis of the treatment of anti-NMDAR encephalitis: Analysis, equipoise, and the urgent need for evidence over anecdote

Abstract

Background

There are no FDA-approved treatments for anti-N-methyl-d-aspartate receptor encephalitis (NMDARE), and no prospective, multicenter clinical trials have been completed to provide evidence for management of this disease. We evaluated changes in treatment strategies and outcomes since the previous comprehensive review in 2019.

Methods

A systematic literature review was conducted in PubMed capturing manuscripts published from January 2019 through March 2024. Demographic and clinical data were extracted from articles containing individual immunotherapy data in NMDARE and were compared to a previously published literature review. Studies with ≥10 cases, ≥6 months follow-up, and outcomes reported as favorable (modified Rankin Scale [mRS] 0–2) and poor (mRS 3–5 or 3–6), were grouped and summarized by diagnosis period.

Results

Among 649 patients from 321 articles, first- (from 91.3 % to 98.3 %, p < 0.001) and second-line (from 31.8 % to 42.5 %, p < 0.001) immunotherapy use has increased. The proportion of patients receiving immunotherapy within 30 days of symptom onset increased from 50.1 % to 72.5 % (p < 0.001). Favorable outcome (mRS 0–2) increased from 71.5 % to 76.7 % (p = 0.024), while mortality (6.3 % to 6.9 %, p = 0.714) and relapse rates (12.6 % vs. 13.2 %, p = 0.789) remained unchanged. Data from larger cohort studies of patients diagnosed with NMDARE after 2013 have reported wide variability in the proportion of patients achieving a favorable outcome at final follow-up, ranging from 56 % to 93 %, depending on the institution and follow-up duration.

Conclusions

Since 2019, more patients have been treated early with first- and second-line immunotherapies. Functional outcomes have shown modest improvements, whereas mortality and relapse rates have remained unchanged.