Efficacy and safety of tocilizumab in the chronic phase of febrile infection-related epilepsy syndrome: a retrospective cohort study.

BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) is a rare and severe epileptic encephalopathy characterized by refractory seizures following a febrile infection. FIRES is a subtype of new-onset refractory status epilepticus with an unknown etiology. Tocilizumab is an interleukin-6 receptor antagonist which has been recommended as an anti-inflammatory treatment for the acute phase of FIRES. However, the efficacy of tocilizumab for the chronic phase of FIRES remains unclear. This study aimed to analyze the efficacy and safety of tocilizumab in the treatment of pediatric patients with FIRES during the chronic phase. METHODS: We conducted a retrospective cohort study in pediatric patients with FIRES during the chronic phase who received tocilizumab treatment. The primary outcome was the response rate at 16 weeks after tocilizumab initiation, defined as the proportion of pediatric patients who achieved a 50% or greater reduction in seizure frequency. Secondary outcomes included the response rate at 28 weeks, treatment-related adverse events, and changes in the modified Rankin Scale (mRS) scores. The response rate to tocilizumab treatment, incidence of adverse reactions and factors related with the efficacy of tocilizumab were analyzed. RESULTS: Twenty-seven pediatric patients with chronic-phase FIRES were included. The median duration of seizures at tocilizumab initiation was 16 months [interquartile range (IQR): 6-34 months]. All patients received a median of four (IQR: 3-6) doses of tocilizumab. Most patients (81.5%, 22/27) did not require additional anti-seizure medications during the entire treatment period. After 16 weeks of treatment, 63.0% (17/27) of patients achieved a 50% or greater reduction in seizure frequency, and 7.4% (2/27) were seizure free; 70.4% (19/27) of the patients showed improvements in mRS scores. After 28 weeks, the response rate was 48.1% (13/27). The most common adverse events were neutropenia (33.3%, 9/27) and infections (14.8%, 4/27). CONCLUSIONS: Tocilizumab is effective in the treatment of epilepsy in the chronic phase of FIRES. Tocilizumab can reduce the seizure frequency in pediatric patients with FIRES and is relatively safe.