Efficacy and safety of different oral prednisone tapering course in adult anti-NMDAR encephalitis: A multicenter prospective cohort study

Background In adult N-methyl-D-aspartate receptor (NMDAR) encephalitis, corticosteroids are commonly used as first-line treatment. However, the optimal oral prednisone tapering (OPT) following intravenous methylprednisolone pulse therapy remains unclear. We aim to compare the efficacy and safety of different OPT course in NMDAR encephalitis. Methods The CHASE study, a multicenter, prospective, observational cohort study, enrolled patients diagnosed with autoimmune encephalitis from October 2011 to March 2023. Patients were divided into three groups based on the duration of oral prednisone tapering: ≤3 months (Group ≤ 3 mo), 3–6 months (Group 3–6 mo), and > 6 months (Group>6 mo). Kaplan-Meier plots were generated for time-to-event endpoints, including the first relapse within 2 years and total recovery within 2 years, with sensitivity analyses and subgroup analyses conducted to assess estimate robustness. Results Among 666 screened patients, 171 (median [IQR] age was 27 [21.0-36.5] years, 55.0% were female) met selection criteria. The proportion of responders at 3 months was higher in Group ≤ 3 mo (OR, 9.404 [95% CI 2.741 to 32.257]) and Group 3–6 mo (OR, 5.360 [95% CI 1.477–19.453]) than in Group > 6 mo. Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at 12 months after treatment were higher in Group >6 mo than in Group ≤ 3 mo and Group 3–6 mo (2.5 [IQR: 1.0–4.0] vs. 1 [IQR: 0.0–2.0] vs 1 [IQR: 0.0–2.0]). However, after propensity score matching, these differences disappeared. Weight gain was more frequent in the Group > 6 months than in Group ≤ 3 months (80.0% [95% CI 61.6–98.4%] vs. 33.3% [95% CI 14.1–52.6%]). No significant differences were found in modified Rankin Scale (mRS) scores, relapse rates within 2 years, full recovery within 2 years, time to recovery, impact of residual symptoms, or CASE score changes. Conclusions Extending oral prednisone beyond 3 months did not significantly improve outcomes but increased the risk of adverse events, particularly weight gain. This recommends evaluating the possibility of shortening the duration of oral prednisone after a thorough patient assessment. Trial Registration: The trial was registered on Cinese Clinical Trial Registry (ChiCTR1800019762).