OBJECTIVES: The purpose of this study was to evaluate the efficacy of Efgartigimod (EFG) in anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis patients during acute attacks. METHODS: A case-control study was designed to compare 26 anti-NMDAR encephalitis patients who were treated with EFG, and 15 patients with intravenous immunoglobulin (IVIG), and 23 patients with immunoadsorption with staphylococcal protein A column (SPA-IA) treatment. RESULTS: At baseline, no significant differences in mRS scores were observed among the EFG, IVIG, and SPA-IA groups of anti-NMDAR encephalitis patients. When compared with the IVIG group, patients treated with EFG had significantly decreased serum IgG levels. Compared with the SPA-IA group, EFG-treated patients had lower CSF anti-NMDAR antibody titers at admission (p = 0.039) and higher post-treatment IgG levels (p = 0.002). When compared with the IVIG group, SPA-IA patients had higher CASE scores (p = 0.022) and baseline IgG levels (p = 0.023). All groups improved the symptoms of anti-NMDAR encephalitis patients after treatment during acute attacks, with significant decreases in mRS and CASE scores from admission to discharge (p <
0.01). In the EFG and SPA-IA groups, there was a significant reduction in anti-NMDAR antibody titers in both CSF and serum (p <
0.01), while no remarkable decrease was found in the IVIG group. Additionally, serum IgG levels significantly decreased in both the EFG and SPA-IA groups post treatment and during the 1-month follow-up. By the 3-month of follow-up, IgG levels in the blood of both groups remained below the baseline levels. CONCLUSION: EFG could be an elegant alternative to both IVIG and SPA-IA therapies for anti-NMDAR encephalitis during acute attacks. It has a better effect on reducing antibody titers than IVIG and is comparable to SPA-IA therapy, and no serious adverse events were observed during infusion.