Abstracts

Clinical trials are not designed to detect rare adverse events or adverse events with a long induction time. In contrast, a rigorous prospective post-marketing study that catalogues data from clinical practice can detect these types of adverse events while avoiding the biases that are sometimes found in retrospective trials. This type of survey was initiated to detect rare or late adverse events caused by the use of pregabalin., Epilepsy patients started on pregabalin were enrolled prospectively as our center[apos]s contribution to the multicenter Post-marketing Antiepileptic Drug Survey. 40 patients were enrolled at our center so far., 23 patients with partial seizures have three month follow up. The average age was 43.6 years. The mean duration of epilepsy was 25 years, and the mean number of concomitant antiepileptic drugs was 2.7. The initially prescribed titration dose was a median 300mg and at 3 months the median dose was unchanged. 78% reported at least one adverse event. The common adverse events were: weight gain, ataxia or dyscoordination, fatigue, dizziness, headache, myoclonus and edema. One patient reported symptoms consistent with subacute onset of bilateral carpal tunnel syndrome. The median weight gain was 6 lbs, and the mean was 4.6 lbs. 56% of patients were found to have had some weight gain, and those that did gained an average of 8.5 lbs. 22% lost an average of 4.6 pounds. The discontinuation rate was 17.4%. 52.2% of patients reported a decrease in seizure frequency., These results are similar to those described in one of the pivotal clinical trials assessing the efficacy of pregabalin[1]. The population of the current study differed from the clinical trial in 2 ways: the patients were older in age by 4 years and the number of concomitant antiepileptic drugs used at initiation was 2.7 versus the 1.7 in the randomized controlled trial. Interestingly, the rate of adverse events was close at similar dosages (78% vs. 84%). The most common adverse events were detected, and the weight gain data are very close to that reported for the highest dose in the clinical trial (4.6 vs. 5.0 lbs). In addition, the discontinuation rate was similar (17.4% vs. 14%). It is very encouraging that these early data so closely parallel that of a published prospective clinical trial. This suggests that the study design is sound and that it will be a sensitive tool for detecting adverse drug events such as those that are rare or that manifest later in treatment. Further follow-up for the full cohort will be presented at the meeting.
[1] French JA, Kugler AR, Robbins JL, Knapp LE, Garofalo EA. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures.Neurology. 2003 May 27;60(10):1631-7., (Supported by Current funding by Pfizer. Recent funding UCB, Ortho-McNeil, Glaxo-Wellcome, Elan Pharmaceuticals, Novartis.)