Substitution has better efficacy than add-on therapy for patients with focal epilepsy after their first antiepileptic drug treatments fail

Abstract

A B S T R A C TPurpose: This study is to compare the efficacy of substitution with add-on therapy in patients with focal epilepsy, whose first monotherapy has failed after receiving usual treatments. Methods: This is a prospective, long-term, non-randomized observational cohort study. Data were collected from Wenzhou Epilepsy Follow Up Registry Database. Focal epilepsy patients from January 2003 to June 2015, whose first monotherapy had failed, were registered. The total observation period was three years. The major outcome measure was seizure remission rate. The secondary outcome measures included retention rates and incidences of intolerable adverse events. Results: A total of 596 patients were included, among them 209 received substitution therapy, and 387 received add-on therapy. Seizure remission rates were 56.5% by substitution therapy and 39.0% by add-on therapy, respectively (p = 0.025). Retention rate was 49.3% by substitution therapy, and 36.2% by add-on therapy (p = 0.031). Incidence of intolerable adverse events for substitution and add-on was 4.8% and 7.2%, respectively (p = 0.243). There were 457 patients who failed to the first monotherapy due to lack of efficacy. In these patients, seizure remission rates of substitution and add-on were 51.0% and 38.1%, respectively (p = 0.171). Retention rates were 48.1% and 36.0%, respectively (p = 0.136). And, incidences of intolerable adverse events were 2.9% and 6.8%, respectively (p = 0.137). Conclusion: The seizure remission rate and retention rate of substitution therapy are better than those of add-on therapy for focal epilepsy patients whose first monotherapy fails.

Evaluation of one-year effectiveness of clobazam as an add-on therapy to anticonvulsant monotherapy in participants with epilepsy having uncontrolled seizure episodes: An Indian experience

“…In this pragmatic study, the treating neurologists chose to add clobazam as per their own discretion. Similar to our study, seizure freedom rates ranging from 50% to 60% after the failure of initial monotherapy have been reported by other observational studies [26,27]. Although a seizure freedom rate of >70% should be evaluated in the context of nonblinded observational nature of study, it does provide preliminary evidence that clobazam is an effective drug as first add-on therapy.…”

Starting a new anti‐seizure medication in drug‐resistant epilepsy: Add‐on or substitute?

“…These trial designs, despite their shortcomings, provide evidence of efficacy of a substitution approach in DRE and have led to several ASMs being approved for use as monotherapy. Randomized studies comparing add‐on to substitution in patients with relatively newly diagnosed focal epilepsy failing initial ASM monotherapy have shown no difference in seizure outcomes, 30,31 but some observational studies suggest that substitution is associated with better seizure outcome and retention rate 32 . Prospective observational studies assessing remission in DRE cohorts do not explicitly analyze seizure outcomes by mode of drug introduction, 2,3 but one recent longitudinal cohort study showed no differences in the two approaches 26 …”

The importance of drug titration in the management of patients with epilepsy

“…Initial treatment with ASM monotherapy is standard; however, ASM conversion may be required when the initial drug fails, either due to lack of efficacy or tolerability [48,51]. Although the benefits of substitution over add-on therapy are still a matter of debate [17,[52][53][54][55], a trial with one or more additional monotherapies is common before starting chronic polytherapy.…”