Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.
New Onset Epilepsy: Trials and Implications
To advance the knowledge of practicing neurologists with regard to available data and first-line treatment strategies in patients with new-onset epilepsy.
This activity is designed for neurologists. No prerequisites required.
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:
- Analyze the trial design and results of recent monotherapy trials and use such as an illustration of the challenges and controversies surrounding clinical trials that compare traditional and modern antiepileptic drugs (AEDs).
- Understand the rationale and methodology of AED trials in new-onset epilepsy.
- Summarize the available data comparing older and modern AEDs.
- Interpret and apply clinical trial results to patient management.
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.
The estimated time to complete this educational activity: 2 hours.
Release date: March 15, 2005. Expiration date: March 15, 2007.
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review
of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.
This program is supported by an educational grant from Ortho-McNeil Pharmaceutical, Inc.
Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:
Peter W. Kaplan, MBBS, FRCP
Professor of Neurology
Johns Hopkins University School of Medicine
Chairman of Neurology
Director of Epilepsy and EEG
Johns Hopkins Bayview Medical Center
• Dr Kaplan reports receiving grants/research support from GlaxoSmithKline and Pfizer Inc.
Jacqueline A. French, MD
Professor of Neurology
University of Pennsylvania
• Dr French reports receiving grants/research support from Abbott Laboratories, Elan Corporation, GlaxoSmithKline, Johnson & Johnson, MedPointe Pharmaceuticals, Novartis Pharmaceuticals USA, Ortho-McNeil Pharmaceutical, Inc, Pfizer Inc, and UCB Pharma; serving as a consultant to Abbott Laboratories, Cyberonics, Inc, Eisai Inc, Elan Corporation, GlaxoSmithKline, MedPointe Pharmaceuticals, Novartis Pharmaceuticals USA, Ortho-McNeil Pharmaceutical, Inc, Pfizer Inc, Schwarz Pharma, and UCB Pharma; and serving on the speakersÕ bureaus for Elan Corporation, GlaxoSmithKline, MedPointe Pharmaceuticals, Novartis Pharmaceuticals USA, Ortho-McNeil Pharmaceutical, Inc, Pfizer Inc, and UCB Pharma.
James W. Wheless, MD
Professor of Neurology and Pediatrics
Texas Comprehensive Epilepsy Program
University of Texas - Houston
• Dr Wheless reports receiving grants/ research support from Abbott Laboratories, Cyberonics, Inc, Ortho-McNeil Pharmaceutical, Inc, and UCB Pharma; serving as a consultant to Abbott Laboratories, Cyberonics, Inc, Marinus Pharmaceuticals, Inc, Novartis Pharmaceuticals USA, Ortho-McNeil Pharmaceutical, Inc, Pfizer Inc, Questcor Pharmaceuticals, Inc, and UCB Pharma; and receiving honoraria from Cyberonics, Inc, GlaxoSmithKline, Novartis Pharmaceuticals USA, Ortho-McNeil Pharmaceutical, Inc, and UCB Pharma.
Eric Kossoff, MD
Assistant Professor of Neurology and Pediatrics
Johns Hopkins Hospital
• Dr Kossoff reports receiving grants/research support from UCB Pharma and serving on the speakers' bureau for GlaxoSmithKline, Novartis Pharmaceuticals USA, and Ortho-McNeil Pharmaceutical, Inc.
Notice: In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices. The following faculty members have disclosed that their articles have referenced the following unlabeled/unapproved uses of drugs or devices:
Dr French—gabapentin, lamotrigine, topiramate.
Dr Wheless—carbamazepine, gabapentin, topiramate.
Dr Kossoff—gabapentin, levetiraretam, pregabalin, tiagabine, topiramate, zonisamide.
Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.
The Role of Clinical Trials in the Management of New-Onset Epilepsy
Peter W. Kaplan, MBBS, FRCP*
Every year, 180 000 people in the United States experience the new onset of recurrent unprovoked seizures and are diagnosed with epilepsy.1 The majority of these patients will require lifelong treatment with antiepileptic drugs (AEDs). In the last 10 years, 7 new drugs have been approved by the US Food and Drug Administration for the treatment of epilepsy. While providing the clinician with a wider range of treatment options, the development of modern AEDs has also vastly increased the complexity of medical decision making. The traditional AEDs have been used for decades, and their efficacy and side-effect profiles are well established. In contrast, the neurology community is still in the process of delineating the precise role that modern AEDs will play in the management of newly diagnosed patients. Despite suboptimal outcomes in patients treated with traditional AEDs, few clinical trials have directly compared modern AEDs with the traditional medications.
The specific design of these clinical trials, as well as the optimal manner in which they are conducted and interpreted, remain an area of debate in the academic community, and the results of these trials have important implications for all clinicians who care for patients with epilepsy. This issue of Advanced Studies in Medicine serves to advance the knowledge of practicing neurologists with regard to available data and first-line treatment strategies in patients with epilepsy. The monograph will also provide the academic neurology community and clinical investigators with insight into the optimal methodology of clinical trial design, in the hope of facilitating the development of clinically relevant studies that truly assess the efficacy of modern AEDs and provide a meaningful comparison between modern and traditional treatments.
The article by Dr James W. Wheless provides an overview of monotherapy studies conducted in patients with new-onset epilepsy. Although few in number, these studies provide critical data on the efficacy and safety of AEDs in newly diagnosed patients.
Dr Wheless also examines some of the methodological and ethical challenges that are inherent in the design and interpretation of monotherapy trials. It is often difficult to formulate a clinical trial that accurately reflects the intricacies of everyday clinical practice, and this may limit the ability to extrapolate trial results to patient care. Dr Wheless emphasizes the need for future clinical trials in this area, and particularly for studies that examine the impact of AED therapy on quality of life.
The clinician interview with Dr Jacqueline A. French discusses the complexities of treating patients with new-onset epilepsy, with specific focus on applying clinical trial results to patient care. Dr French explains which outcomes measurements are most relevant to clinicians, and describes her approach to selecting the most appropriate AED for patients with newly diagnosed epilepsy. Given the many available medications and the few available clinical trials, physicians must interpret trial data within the context of their own clinical experience, established practice guidelines, and the individual needs of each patient.
In the accompanying commentary, Dr Eric Kossoff provides a further perspective on the usefulness and applicability of clinical trials in new-onset epilepsy, focusing on the need for rational polytherapy trials, nontraditional outcomes measures, and an increase in the number of studies performed in the pediatric population.
The last article by Dr Michael Privitera et al is an example of one of the few clinical trials to compare a new-generation AED with traditionally used medications. In this double-blind comparison study, patients with new-onset epilepsy were randomized to receive carbamazepine, valproate, or topiramate, and were followed for 6 months. The authors found no statistically significant difference between the 3 medications in efficacy measures, but did note that topiramate was associated with the fewest discontinuations due to adverse events.
The development of novel AEDs has broadened treatment options for patients with new-onset epilepsy, and has required the neurology community to develop rigorous and relevant clinical trials, and then to interpret these data in a way that will help guide therapeutic decisions. This issue of Advanced Studies in Medicine provides an overview of the trials that have been conducted to date, examines their implications for clinical practice, and offers insight into the development of future studies that will further expand our knowledge of epilepsy treatment.
1. Begley CE, Famulari M, Annegers JF, et al. The cost of epilepsy in the United States: an estimate from population-based clinical and survey data. Epilepsia. 2000;41(3):342-351.
*Professor of Neurology, Johns Hopkins University School of Medicine; Chairman of Neurology, Director of Epilepsy and EEG, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
Address correspondence to Peter W. Kaplan MBBS, FRCP, Johns Hopkins Bayview Medical Center, 4940 Eastern Ave, Baltimore, MD 21224. E-mail: email@example.com.