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.