AT AES 2016
HOUSTON (FRONTLINE MEDICAL NEWS) – Fewer than 8% of adult patients with drug-resistant epilepsy would have been recruitable for recent phase II and III trials of new antiepileptic drugs (AEDs), results from a single-center study showed.
The findings underscore a need to rethink how phase II and III trials of AEDs are conducted, Bernhard J. Steinhoff, MD, said in an interview prior to the annual meeting of the American Epilepsy Society. “In spite of the marketing of numerous new antiepileptic drugs, the percentage of drug-resistant epilepsies has remained almost unchanged,” said Dr. Steinhoff of the Kork (Germany) Epilepsy Center. “I am not aware that anybody involved in the issue of clinical trials with AEDs addressed the problem [of] whether the pivotal trials really cover the patients the new AEDs are developed for: namely, patients with drug-resistant epilepsies. Every time we start with a new drug after licensing, we realize that we have no clue whether this drug will be appropriate for our difficult-to-treat patients. We wondered whether the design of the usual phase II and III randomized controlled trials covers an acceptable percentage of AED-resistant epilepsy patients.”
To find out, he and his associates collected data on 216 consecutive adult outpatients with drug-resistant epilepsies as defined by the recent International League Against Epilepsy classification . They assessed whether these patients would have been recruitable for the last five phase II and III trials that have been performed at the Kork Epilepsy Center. Of the 216 patients, only 14 (7.4%) would have fulfilled the inclusion criteria of all five studies without meeting exclusion criteria. The five major reasons for exclusion were: treatment with enzyme-inducing AEDs (47.2%); too few seizures per definite periods in spite of AED resistance (46.3%); EEG signs for generalized epileptogenesis (31.5%); intellectual disability or legal representatives (29.6%); and long distance between home and center that prevents frequent visits as required by the study protocol (27.3%).
“The result was frightening because less than 10% [of patients] would have been covered by the trials,” Dr. Steinhoff said. “Therefore, we suggest that a bad trials strategy may be responsible for the fact that the percentage of drug-resistant patients has not been markedly reduced by more than 15 new AEDs that were introduced during the recent years.” He added that pivotal trials with new AEDs “show superiority over placebo as add-on in an extremely limited group of difficult-to-treat patients. After licensing and marketing, we start to learn whether a new AED is appropriate for our drug-resistant patients.”
Medical writing was funded by an unrestricted grant from UCB. Dr. Steinhoff reported having no financial conflicts.