Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China

Correspondence: Xiang Ma, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian City, Liaoning Province, People’s Republic of China, Tel +8618098876399, Email [email protected]

We read with great interest the study by Deng et al, which provides valuable real-world evidence on tocilizumab (TCZ) use in children with cryptogenic febrile infection-related epilepsy syndrome (FIRES) during both acute and chronic phases.1 This work is important because it extends the discussion from whether IL-6 receptor blockade may reduce seizures to how TCZ should be positioned within a staged immunomodulatory strategy.

A key implication is that the therapeutic window for TCZ in FIRES may not be a simple division between early efficacy and late futility. Early intervention remains biologically and clinically compelling, particularly given the time-critical nature of super-refractory status epilepticus. However, the observation that some patients treated beyond the earliest window still improved suggests that FIRES may also involve a persistent neuroinflammatory state in selected patients.2,3 This does not weaken the case for early treatment; rather, it argues for better markers of ongoing inflammatory activity when treatment is delayed. Experience from other immune-mediated diseases offers a useful, though not directly equivalent, perspective. In refractory non-infectious uveitis, TCZ has been used after failure of corticosteroids, conventional immunosuppressants, and anti-TNF agents, with substantial rates of inflammatory control and macular edema resolution.4 Although uveitis and central nervous system inflammation differ fundamentally in immune anatomy and disease tempo, this cross-disciplinary evidence supports the broader principle that targeted therapy against persistent inflammatory pathways should not be dismissed solely on the basis of time from onset.

The study also highlights the need to move beyond single-marker or single-outcome assessment. Serum or cerebrospinal fluid IL-6 may support the rationale for TCZ, but clinical response may not parallel a straightforward decline in measured cytokine levels. Future FIRES studies may therefore benefit from a treat-to-target framework integrating seizure burden, quantitative recovery of EEG background activity, MRI evolution, anesthetic and antiseizure medication reduction, cytokine trajectories, exploratory neuroinflammatory biomarkers such as CSF neopterin or quinolinic acid where available, functional recovery, and longitudinal safety monitoring.5

Overall, Deng et al provide an important contribution to the evolving role of TCZ in FIRES. The next step is to define not only whether TCZ works, but when it should be started, which patients are most likely to benefit, how long treatment should continue, and which clinical or biological targets should guide adjustment.

Data sharing does not apply to this communication as no data were created or analyzed in this communication.

Y.Z.: Conceptualization, Writing – Original Draft.

H.C.: Conceptualization, Writing – Review & Editing.

X.M.: Conceptualization, Writing – Review & Editing, Supervision.

Yujie Zhang and Haixing Cao share first authorship.

All authors gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

This work was financially supported by grants from the National Natural Science Foundation of China (81271022).

The authors reported no potential conflict of interest in this communication.

1. Deng X, Chen S, Yin F, et al. The clinical outcomes of tocilizumab usage in cryptogenic febrile infection-related epilepsy syndrome at both acute and chronic phase: a retrospective study. J Inflamm Res. 2026;19:584971. doi:10.2147/JIR.S584971

2. Aledo-Serrano A, Hariramani R, Gonzalez-Martinez A, et al. Anakinra and tocilizumab in the chronic phase of febrile infection-related epilepsy syndrome (FIRES): effectiveness and safety from a case-series. Seizure. 2022;100:51–2. doi:10.1016/j.seizure.2022.06.012

3. Jun JS, Lee ST, Kim R, Chu K, Lee SK. Tocilizumab treatment for new onset refractory status epilepticus. Ann Neurol. 2018;84(6):940–945. doi:10.1002/ana.25374

4. Cao H, Bian K, Ma C, Zhang N, Ma X. Tocilizumab for non-infectious uveitis: a systematic review. J Inflamm Res. 2025;18:13117–13138. doi:10.2147/JIR.S533011

5. Dale RC, Thomas T, Patel S, et al. CSF neopterin and quinolinic acid are biomarkers of neuroinflammation and neurotoxicity in FIRES and other infection-triggered encephalopathy syndromes. Ann Clin Transl Neurol. 2023;10(8):1417–1432. doi:10.1002/acn3.51832