To compare the efficacy and safety of different oral prednisone tapering (OPT) course in Anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-like 2 (Caspr2) encephalitis.

Corticosteroids are the most commonly used first-line treatment for acute anti-LGI1/Caspr2 encephalitis, but the optimal oral prednisone regimen following intravenous methylprednisolone remains elusive.

Among 675 screened patients, 70 (mean age 48.0 ± 16.4 years, 62.9% female) met selection criteria. Patients in Group ≤ 3 months had a higher cumulative hazard of first relapse than those in Group >3 months within 2 years (PSM-adjusted HR, 0.215; 95% CI 0.047 to 0.986, P=0.030). No significant difference was observed in total recovery rate, the proportion of responders, modified Rankin Scale (mRS) score, mRS score change and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) score. CASE score change in Group > 3 months were higher than those in Group ≤ 3 months at multiple follow-up points. Adverse events were higher in Group >3 months than in Group ≤3 months (26 [92.9%] vs 23 [54.8%], PSM-adjusted P= 0.022).

Our study suggests that a longer oral prednisone duration is associated with a lower relapse risk in anti-LGI1/Caspr2 encephalitis. While the total recovery rate did not differ significantly, the increased incidence of adverse events in the prolonged therapy group warrants careful consideration. These findings contribute to the evolving understanding of optimal treatment durations in autoimmune encephalitis and emphasize the need for individualized therapeutic approaches.