Effectiveness and safety of efgartigimod in patients with anti-NMDAR or anti-LGI1 encephalitis and its 18F-DPA714 PET imaging evaluation: A multicenter, single-arm, prospective, observational real-world study.

BACKGROUND: Efgartigimod disrupts the recycling of pathogenic IgG autoantibodies and may represent a candidate therapy for autoimmune encephalitis. This real-world study evaluated the clinical efficacy, safety, and impact of efgartigimod on brain inflammation.

METHODS: This multicenter, single-arm, prospective, observational real-world study enrolled 18 patients, including 10 with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and 8 with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. Participants received intravenous efgartigimod at a dose of 10 mg/kg weekly for a total of two to four doses, with or without concomitant immunosuppressive therapy. Anti-NMDAR-IgG/LGI1-IgG antibody titers, modified Rankin scale (mRS), Clinical Assessment Scale in Autoimmune Encephalitis (CASE), Montreal Cognitive Assessment, Mini-Mental State Examination, and Glasgow Coma Scale scores were assessed at baseline and at 1, 2, 3, 8, and 12 weeks after treatment. 18F-DPA714 positron emission tomography/magnetic resonance imaging was used to monitor brain inflammation in a subset of patients. Analyses were performed using SPSS 26.0 and Prism 10.0. Non-parametric tests, including Wilcoxon signed-rank, Mann-Whitney U, and Friedman tests with Bonferroni post hoc correction, were applied. Two-tailed p < 0.05 indicated statistical significance; corrected p < 0.01 was applied for five longitudinal pairwise comparisons.

RESULTS: At the final follow-up, median mRS scores in patients with anti-NMDAR encephalitis decreased significantly from 3 (range, 1-5) before treatment to 1 (range, 0-3) after treatment (Z = -2.588, p = 0.007). Median CASE scores decreased from 7.5 (range, 1-27) to 1.5 (range, 1-7) post-treatment (Z = -2.714, p = 0.005). In patients with anti-LGI1 encephalitis, CASE scores decreased markedly from 3 (range, 1-7) to 1.5 (range, 0-2) at the last visit (Z = -2.154, p = 0.046). All 18 patients underwent baseline imaging, and 7 patients underwent follow-up PET/MRI examinations. A subset of patients (n = 4; three with anti-NMDAR encephalitis and one with anti-LGI1 encephalitis) showed reduced uptake in specific brain regions accompanied by symptom improvement. Both initial and follow-up imaging results were negative for the remaining three patients. Comparative analysis of efgartigimod monotherapy versus combination therapy with glucocorticoids and immunosuppressants revealed no significant differences in key outcomes, indicating that the therapeutic effect was independent of concomitant medication use. Efgartigimod was well tolerated. One patient (1/18) developed mild pneumonia, but no other serious adverse events were reported.

CONCLUSION: Efgartigimod may represent a novel therapeutic option for anti-NMDAR and anti-LGI1 encephalitis, potentially improving clinical outcomes in affected patients.

REGISTRATION INFO: This study was registered at the National Clinical Research Center (https://www.medicalresearch.org.cn; No. MR-31-24-053225).