Early tocilizumab and outcomes in acute necrotizing encephalopathy
Velda X Han, Prithuja Poudyal, Vanessa Lee, Arushi Gahlot Saini, Shekeeb S Mohammad, Sekhar C Pillai, Gouri Rao Passi, Naveen Sankhyan, Ahmad Rithauddin Mohamed, Lokesh Lingappa, Hiroshi Sakuma, Russell C Dale, Ming Lim, Terrence Thomas,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.