Cumulative thalidomide exposure, peripheral neuropathy, and clinical outcomes in pediatric and very early-onset inflammatory bowel disease: a retrospective cohort study.

BACKGROUND: Thalidomide serves as a rescue therapy for refractory pediatric Inflammatory Bowel Disease (pIBD), but its use is constrained by the risk of thalidomide-induced Peripheral Neuropathy (TiPN). The quantitative relationship between cumulative dose and TiPN, as well as the risk profile in the specific population of Very Early-Onset IBD (VEOIBD), lacks precise evaluation. METHODS: We conducted a single-center, retrospective cohort study of children with IBD treated with thalidomide from 2018 to 2025. We compared cumulative thalidomide doses between TiPN and non-TiPN groups and employed ROC curve analysis to determine a predictive dose threshold. The cohort was further stratified into VEOIBD and pIBD groups to compare dynamic inflammatory marker changes and overall drug tolerability. RESULTS: Among 49 included patients, the incidence of TiPN was 26.5% (13/49). The cumulative thalidomide dose was significantly higher in the TiPN group (median 19.5 g vs. 8.35 g, p = 0.008). A cumulative dose threshold of > 15.38 g predicted TiPN with an AUC of 0.756 (sensitivity 0.722, specificity 0.692). While VEOIBD patients (n = 14) had a distinct disease treatment history, they experienced significantly fewer overall adverse events than pIBD patients (3/14 vs. 19/35, p = 0.04), with no significant difference in TiPN incidence. CONCLUSIONS: Cumulative thalidomide dose is a strong predictor of TiPN in children with IBD. Despite being a more refractory population, VEOIBD patients demonstrated better overall tolerance to thalidomide. Monitoring cumulative dose is crucial for mitigating neurotoxicity and optimizing thalidomide therapy in pIBD.