Efficacy and safety of acute-phase immunotherapy for adult autoimmune encephalitis: a systematic review and network meta-analysis

Background Autoimmune encephalitis (AE) is an immune-mediated inflammatory disorder of the central nervous system associated with substantial morbidity. Acute-phase immunotherapy is crucial for improving outcomes, yet the comparative efficacy and safety of available regimens remain unclear. We therefore performed a Bayesian network meta-analysis to compare acute-phase immunotherapeutic strategies for AE. Methods PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to October 2025 for studies evaluating acute-phase immunotherapy in AE. A Bayesian network meta-analysis was conducted. The primary outcome was change in the modified Rankin Scale (mRS) after treatment; adverse events were secondary outcomes. Effects were expressed as mean differences (MD) and risk ratios (RRs) with 95% credible intervals (CrIs). The surface under the cumulative ranking curve (SUCRA) was used to rank interventions. Results Eleven studies (1,359 patients) were included, evaluating seven strategies: intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIG), IVMP+IVIG, IVMP+plasma exchange (PE), IVMP+IVIG+PE, IVMP+immunoadsorption (IA), and IVMP+efgartigimod (EFG). For efficacy, IVMP+EFG ranked highest in mRS improvement among the included regimens (MD = −0.99, 95% CrI −1.30 to −0.68; SUCRA = 95%), followed by IVMP+IA (MD = −0.87; SUCRA = 88%). IVMP+PE ranked lowest (MD = 0.32; SUCRA = 0.2%). For safety, IVIG monotherapy had the lowest adverse-event risk (RR = 0.51, 95% CrI 0.24 to 0.97), whereas IVMP+PE had the highest risk (RR = 3.10, 95% CrI 0.92 to 9.60). Conclusion Acute-phase immunotherapy for AE should be individualized by disease severity and antibody subtype. Consistent directional findings were observed in the anti-NMDAR subgroup and, separately, in the subgroup with baseline mRS ≥3. IVMP+EFG and IVMP+IA ranked favorably for short-term functional improvement, although the evidence was based mainly on observational studies and small sample sizes. IVIG remained a reasonable option given its favorable safety profile. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251085606 , identifier CRD420251085606.