Early tocilizumab and outcomes in acute necrotizing encephalopathy.

AIM: To evaluate the timing and safety of tocilizumab in acute necrotizing encephalopathy (ANE). METHOD: This was a multicentre retrospective study evaluating outcomes (modified Rankin Scale [mRS]) in children with ANE treated with tocilizumab. A logistic regression model determined a cut-off for outcomes (binary good [mRS 0-2] vs poor [mRS 3-5]) according to day of tocilizumab administration, enabling a dichotomy of 'early' and 'late' treatment groups. Expected outcomes according to ANE severity score (ANE-SS) in early-treatment and late-treatment groups were compared against reference data (conventional therapy, no tocilizumab) for outcomes according to risk category (medium risk: ANE-SS score 2-4; high risk: ANE-SS score ≥5). RESULTS: From 2018 to 2023, 63 children (mean age 6 years 0 months [range: 8 months-15 years 4 months]; 33 males, 30 females) were treated with tocilizumab, alongside corticosteroids in all and intravenous immunoglobulin in 33 (52.4%). Logistic regression defined an optimal treatment window of ≤3.3 days. Compared to the reference data, early tocilizumab (≤ 72 hours after onset, n = 49) was associated with good outcomes in both high-risk (OR = 11.43, 95% confidence interval [CI] = 1.64-127.4, p = 0.01) and medium-risk (OR = 12.80, 95% CI = 2.15-67.8; p = 0.006) ANE-SS categories. No tocilizumab-related adverse events were reported. INTERPRETATION: Early tocilizumab treatment was associated with improved outcomes in severe ANE, with no adverse events, compared to conventional therapy alone.