Comparing the efficacy of first-line immunotherapies in autoimmune encephalitis: a scoping review

This scoping review aims to explore research comparing the efficacy of steroids, IVIG, and PLEX immunotherapies for autoimmune encephalitis (AE) to determine which treatment(s) lead to better clinical outcomes.

Autoimmune encephalitis is a neurological disease treated with several different immunotherapies, including steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PLEX). Steroids are often first-line, but it is unclear whether certain immunotherapies are more clinically efficacious.

A comprehensive search of the PubMed, Cochrane, and Google Scholar databases from inception to July 1, 2025, was used to identify papers using the following search terms: "autoimmune encephalitis," "encephalitis," "IVIG or intravenous immunoglobulin," "PLEX or plasma exchange," "corticosteroids," and "monotherapy."

We identified 14 publications that fell within our search criteria. 10 of the 14 papers were retrospective studies. The remaining papers included 3 prospective studies and 1 single-arm open label clinical trial. Clinical outcomes were assessed using the modified Rankin scale (mRS). At least 5 papers examined clinical outcomes in children, and all 14 papers assessed clinical outcomes in the adult population. 1 paper did not provide information on participant age ranges. 10 papers included data assessing the efficacy of steroids in AE, with 9 papers providing data that steroids improved clinical outcomes. 7 papers assessed the clinical efficacy of IVIG where 6 papers provided data on mRS improvement in AE. Finally, 3 papers assessed mRS improvement with PLEX, where all 3 papers showed PLEX led to clinical improvement. However, it should be noted that several studies had serious to critical risk of bias and moderate to high methodological concern, impeding the reliability of each study's findings.

There is limited data separately evaluating first-line immunotherapies to assess whether steroids, PLEX, or IVIG are clinically superior. Thus, exploring which immunotherapy correlates most strongly with improved clinical outcomes through additional prospective studies and randomized clinical trials would be beneficial. Additionally, further data on which combinations or cycling of therapies (i.e., the "zipper method") are most clinically efficacious, depending on patient presentation, demographics, and pathogenic mechanism would be crucial in developing more comprehensive treatment protocols.