Impact of vigabatrin on risk of relapse of infantile spasms

OBJECTIVE: Vigabatrin is an effective treatment for infantile epileptic spasms syndrome (IESS), but relapse remains a clinical challenge. The ideal dose and duration of treatment after response are unknown. We set out to identify treatment-related predictors of IESS relapse after initial vigabatrin response. METHODS: We conducted a retrospective cohort study of infants with IESS who achieved electroclinical response within 30 days of vigabatrin initiation (alone or with hormonal therapy) and remained in remission for ≥ 30 days. Time to epileptic spasms relapse was analyzed using the Kaplan-Meier procedure and Cox proportional hazards regression. A linear regression-based propensity score (derived from etiology and latency to vigabatrin initiation) was included in Cox models to adjust for treatment duration confounding. Candidate predictors included age at IESS onset, presence of other seizure types at onset, developmental status, prior relapse, vigabatrin dose, and use of dual therapy (concomitant adrenocorticotropic hormone [ACTH] or prednisolone). RESULTS: Of 164 responders, 63 (38%) relapsed at a median of 7.5 months (IQR: 2.4-18.0) after response. Twenty-one (33.3%) relapses occurred following vigabatrin discontinuation. In propensity score-adjusted multivariable regression, increased relapse risk was associated with prior IESS relapse (HR 2.35; 95% CI 1.24-4.45; P = 0.009), other seizure types at IESS onset (HR 2.31; 95% CI 1.31-4.07; P = 0.004), and abnormal development at IESS diagnosis (HR 1.75; 95% CI 1.04-2.95; P = 0.035). Moderate dosing (100-149 mg/kg/day) was protective versus lower doses (HR 0.47; 95% CI 0.25-0.89; P = 0.020). In an underpowered analysis of vigabatrin exposure as a time-varying covariate, ongoing therapy was not significantly associated with latency to relapse (HR 0.77; 95% CI 0.39-1.49; P = 0.436). SIGNIFICANCE: Relapse after vigabatrin response is common and influenced by identifiable clinical factors. Continued vigabatrin treatment (> 100 mg/kg/day) may reduce relapse risk. Prospective validation is warranted to guide individualized relapse prevention strategies. PLAIN LANGUAGE SUMMARY: Infantile Epileptic Spasms Syndrome is a serious seizure disorder of infancy that can recur even after successful treatment with vigabatrin. In this study of 164 infants, we found that relapse was most common among children with prior relapses, other seizure types, or developmental delays. Infants treated with moderate vigabatrin doses (100-149 mg/kg/day) had the lowest relapse rates. These findings may help clinicians identify which infants face the highest risk and tailor treatment accordingly.