AEDs perform largely the same in reducing secondary generalized tonic-clonic seizures

A meta-analysis of clinical trial data has revealed few differences among antiepileptic drugs in reducing the frequency of secondary generalized tonic-clonic seizures.

Claire Hemery of University Claude Bernard, Lyon, France, and her associates studied results from 13 randomized, controlled trials evaluating seven antiepileptic drugs used as adjunct therapy in patients with drug-resistant focal epilepsy (Epilepsia 2014 Sept. 2 [doi:10.1111/epi.12765]). The included trials measured the responder rate, or proportion of patients with 50% or greater reduction in seizure frequency from baseline, for all seizures and secondary generalized tonic-clonic seizures (SGTCS) in particular. SGTCS affect about a third of patients with drug-resistant focal epilepsy and are the main cause of sudden unexpected death in this patient group.

Only three AEDs – lacosamide, perampanel, and topiramate – were shown to be more effective than placebo in responder criteria for SGTCS when used as add-on therapies, with a relative risk of 1.83 for lacosamide (95% confidence interval, 1.19-2.83), 1.41 for perampanel (95% CI, 1.14-1.74), and 1.89 for topiramate (95% CI, 1.34-2.65). Although Ms. Hemery and her colleagues identified one AED, pregabalin, to be significantly less effective than lacosamide, perampanel, or topiramate in reducing SGTCS in this patient group, confidence intervals overlapped for the other study drugs. The researchers wrote that the infrequent and irregular occurrence of SGTCS presented statistical challenges, noting that phase III clinical trials of AEDs “are not designed and powered to appropriately evaluate” this type of seizure. The investigators argued that their findings reinforce the need “to develop alternative designs for the evaluation of new therapeutic interventions in epilepsy, especially in at-risk patients with seizure-related complications and/or comorbidities.”

Ms. Hemery reported no disclosures related to her study, which had no outside funding. One of Ms. Hemery’s coauthors, Dr. Philippe Ryvlin, disclosed receiving fees from Pfizer, Sanofi-Aventis, GlaxoSmithKline, Janssen-Cilag, UCB, Eisai, and Valeant. The study’s corresponding author, Dr. Sylvain Rheims, disclosed receiving fees or funding from UCB, Eisai, GlaxoSmithKline, and Cyberonics.

A meta-analysis of clinical trial data has revealed few differences among antiepileptic drugs in reducing the frequency of secondary generalized tonic-clonic seizures.

Claire Hemery of University Claude Bernard, Lyon, France, and her associates studied results from 13 randomized, controlled trials evaluating seven antiepileptic drugs used as adjunct therapy in patients with drug-resistant focal epilepsy (Epilepsia 2014 Sept. 2 [doi:10.1111/epi.12765]). The included trials measured the responder rate, or proportion of patients with 50% or greater reduction in seizure frequency from baseline, for all seizures and secondary generalized tonic-clonic seizures (SGTCS) in particular. SGTCS affect about a third of patients with drug-resistant focal epilepsy and are the main cause of sudden unexpected death in this patient group.

Only three AEDs – lacosamide, perampanel, and topiramate – were shown to be more effective than placebo in responder criteria for SGTCS when used as add-on therapies, with a relative risk of 1.83 for lacosamide (95% confidence interval, 1.19-2.83), 1.41 for perampanel (95% CI, 1.14-1.74), and 1.89 for topiramate (95% CI, 1.34-2.65). Although Ms. Hemery and her colleagues identified one AED, pregabalin, to be significantly less effective than lacosamide, perampanel, or topiramate in reducing SGTCS in this patient group, confidence intervals overlapped for the other study drugs. The researchers wrote that the infrequent and irregular occurrence of SGTCS presented statistical challenges, noting that phase III clinical trials of AEDs “are not designed and powered to appropriately evaluate” this type of seizure. The investigators argued that their findings reinforce the need “to develop alternative designs for the evaluation of new therapeutic interventions in epilepsy, especially in at-risk patients with seizure-related complications and/or comorbidities.”

Ms. Hemery reported no disclosures related to her study, which had no outside funding. One of Ms. Hemery’s coauthors, Dr. Philippe Ryvlin, disclosed receiving fees from Pfizer, Sanofi-Aventis, GlaxoSmithKline, Janssen-Cilag, UCB, Eisai, and Valeant. The study’s corresponding author, Dr. Sylvain Rheims, disclosed receiving fees or funding from UCB, Eisai, GlaxoSmithKline, and Cyberonics.

A meta-analysis of clinical trial data has revealed few differences among antiepileptic drugs in reducing the frequency of secondary generalized tonic-clonic seizures.

Claire Hemery of University Claude Bernard, Lyon, France, and her associates studied results from 13 randomized, controlled trials evaluating seven antiepileptic drugs used as adjunct therapy in patients with drug-resistant focal epilepsy (Epilepsia 2014 Sept. 2 [doi:10.1111/epi.12765]). The included trials measured the responder rate, or proportion of patients with 50% or greater reduction in seizure frequency from baseline, for all seizures and secondary generalized tonic-clonic seizures (SGTCS) in particular. SGTCS affect about a third of patients with drug-resistant focal epilepsy and are the main cause of sudden unexpected death in this patient group.

Only three AEDs – lacosamide, perampanel, and topiramate – were shown to be more effective than placebo in responder criteria for SGTCS when used as add-on therapies, with a relative risk of 1.83 for lacosamide (95% confidence interval, 1.19-2.83), 1.41 for perampanel (95% CI, 1.14-1.74), and 1.89 for topiramate (95% CI, 1.34-2.65). Although Ms. Hemery and her colleagues identified one AED, pregabalin, to be significantly less effective than lacosamide, perampanel, or topiramate in reducing SGTCS in this patient group, confidence intervals overlapped for the other study drugs. The researchers wrote that the infrequent and irregular occurrence of SGTCS presented statistical challenges, noting that phase III clinical trials of AEDs “are not designed and powered to appropriately evaluate” this type of seizure. The investigators argued that their findings reinforce the need “to develop alternative designs for the evaluation of new therapeutic interventions in epilepsy, especially in at-risk patients with seizure-related complications and/or comorbidities.”

Ms. Hemery reported no disclosures related to her study, which had no outside funding. One of Ms. Hemery’s coauthors, Dr. Philippe Ryvlin, disclosed receiving fees from Pfizer, Sanofi-Aventis, GlaxoSmithKline, Janssen-Cilag, UCB, Eisai, and Valeant. The study’s corresponding author, Dr. Sylvain Rheims, disclosed receiving fees or funding from UCB, Eisai, GlaxoSmithKline, and Cyberonics.