Remission of Epilepsy after Two Drug Failures in Children: A Prospective Study

Objective: Determine the probability of a more than 1-year remission after failure of a second drug in children prospectively followed from initial diagnosis of epilepsy and then from time of second drug failure. Identify prognostic factors for remission after second drug failure. Methods: Of 613 children, 128 did not respond favorably to 2 drugs, had a trial of at least a third drug (median, 3), and were followed for more than 1 year (median, 10.1 years) since second drug failure. Product limit and proportional hazards techniques were used to analyze predictors of any 1-year remission (Rem1) and 1- and 3-year remission at last contact (Rem1/3-LC). Results: Sevency-three patients (57%) had a remission. Repeated remissions and relapses were common. Only 48 (37.5%) achieved Rem1-LC and 28 (23%) Rem3-LC. Idiopathic epilepsy (Rem1: rate ratio [RR], 3.64, p < 0.0001; Rem1-LC: RR, 2.57, p = 0.008) and seizure frequency (Rem1: RR, 0.76, p = 0.003; Rem1-LC: RR, 0.82, p = 0.04 per increase in category) were the most robust predictors. Symptomatic cause was the only correlate of Rem3-LC. Remission before second drug failure did not predict remission after second drug failure. Interpretation: Remission after second drug failure is common but often temporary. Children who have not responded to two appropriate drugs should be carefully evaluated to maximize therapy and possibly considered for more aggressive treatments.