Effectiveness and safety of tocilizumab combined with different high‐dose methylprednisolone regimens for acute necrotizing encephalopathy in children

ABSTRACT Importance Acute necrotizing encephalopathy (ANE) is a rare but life‐threatening pediatric neurological disorder characterized by rapid progression and high mortality. Tocilizumab, an interleukin‐6 receptor antagonist, combined with high‐dose methylprednisolone [MP, ≥20 mg/(kg·day)], may improve outcomes, yet the optimal MP dosing strategy remains uncertain. Objective To evaluate the comparative effectiveness and safety of two high‐dose MP regimens [20 mg/(kg·day) vs. 30 mg/(kg·day)], each in combination with tocilizumab for ANE. Methods This retrospective cohort study included 23 ANE patients treated with tocilizumab and high‐dose MP at Beijing Children's Hospital from January 2023 to January 2025. Patients were divided into two groups based on the initial MP dosage: 20 mg/(kg·day) ( n = 11) and 30 mg/(kg·day) ( n = 12). Primary outcomes included mortality and anti‐inflammatory response. Secondary outcomes were the incidence of severe neurological sequelae, assessed using the pediatric overall performance category (POPC) score, and the frequency of treatment‐related adverse events. Results Overall mortality rate was 26.1% with a lower rate observed in the 30 mg/(kg·day) group (16.7%) compared to the 20 mg/(kg·day) group (36.4%). Most patients (78.3%) had severe ANE (ANE Severity Score ≥5), and 91.3% presented with multi‐organ dysfunction and brainstem involvement. Both groups demonstrated significant reductions in procalcitonin, cerebrospinal fluid protein, and cerebrospinal cytokines after 3 days of MP therapy ( P < 0.05). Compared with the 20 mg/(kg·day) group, the 30 mg/(kg·day) MP group had significantly lower rates of severe neurological sequelae (POPC score 4–6) at discharge (41.7% vs. 90.9%; P = 0.027) and at 6–12 months follow‐up (30.0% vs. 85.7%; P = 0.050). No statistically significant differences in adverse event rates were observed between the two groups ( P > 0.05), and no tocilizumab‐related adverse events were reported. Interpretation In pediatric ANE, tocilizumab combined with 30 mg/(kg·day) MP was associated with improved neurological outcomes compared with 20 mg/(kg·day), with comparable mortality and safety profiles. These findings suggest that a higher initial MP dose may offer neuroprotective advantages, warranting further validation in prospective, multicenter studies.