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Nearly Half Of Patients' Seizure Frequencies Reduced Significantly With Levetiracetam Add-On Therapy

LONDON, ENGLAND -- June 11, 2003 -- Data from a new investigational study on children with highly refractory epilepsy syndromes published today in the European Journal of Paediatric Neurology, Volume 7, Number 3, shows about half of patients observed treated with levetiracetam as an add-on therapy experienced seizure frequency reductions of over 50%.

The open-label add-on study shows that levetiracetam is a well tolerated alternative in refractory childhood epilepsy syndromes, as only a few mild side effects were observed. The study also shows that levetiracetam is effective against both partial and generalised seizures, demonstrating that rapid introduction is feasible and that the possible positive effect of the drug can be seen soon after administration. Levetiracetam is currently indicated as adjunctive treatment of partial onset seizures, with or without secondary generalisation, in adults with epilepsy, and its current marketing authorisation does not include the use in paediatric patients.

The realistic goal of add-on treatment in children with highly refractory epilepsy syndromes is not to achieve seizure freedom but to increase their quality of life by reducing seizures as much as possible without causing (new) side effects. The balance between efficacy and low incidence of adverse events is a difficult one to achieve in the treatment of epilepsy, especially in children with some epilepsy syndromes that tend to worsen over time.

The protocol of the open-label add-on study in children was designed to mimic usual clinical practice as much as possible. Twenty-one children were included in the study lasting 12 weeks. To be eligible, patients had to be between six months and 14 years old and refractory to at least two standard antiepileptic treatments. Levetiracetam was added to the baseline medication with a gradual dose-escalation schedule. Starting dosage was 10mg/kg/day, given in two equally divided doses. Dosage could be increased every fourth day to a designated maximum of 60 mg/kg/day.

Results showed that the final dosage of levetiracetam varied between 17 and 60 mg/kg/day with a median of 37 mg/kg/day. Final dosage was reached in most children between 12 and 16 days after inclusion. Ten children (47%) had an overall reduction of their seizure frequency of more than 50%. Three patients showed a seizure reduction of 90% or more (14.3%), and one child (4.8%) out of the five suffering from Lennox Gastaut syndrome became seizure free. In eight children (38.1%), there was little or no effect with three (14.3%) showing an increase in their seizure frequency. Comparing the effect in generalised, partial and mixed epilepsy syndromes, no significant differences could be found. The best results in generalized seizures were observed in myoclonic seizures, with 7/11 patients (64%) showing a significant (p<0.02) reduction in seizure frequency. Relatively few side effects were noted in the study: non-specific headache in one patient (4.8%) and increased somnolence in two patients (9.5%). Two patients discontinued levetiracetam treatment: one due to increased somnolence and another as a result of increasing behavioural problems. At the end of the study, when the parents were asked if they would like their children to continue levetiracetam, 14 out of 21 decided to do so. In 4 of these cases, despite low efficacy, levetiracetam was continued as parents noted: "…a remarkable increase of alertness, allowing better communication with these children."1

Lead author of the study, Professor Lieven Lagae, MD, PhD, University Hospital Gasthuisberg, Department of Paediatric Neurology, Leuven, Belgium, explained, "Our study has shown for the first time that levetiracetam has a beneficial effect on different seizure types within highly refractive childhood epilepsy syndromes. This is good news for physicians, parents and some children with epilepsy, as it shows a future possible add-on therapy may enhance quality of life in difficult to treat children whose natural course of illness might otherwise be downhill".

Although there have been a few positive studies looking at levetiracetam in children with partial seizures 2,4, to date they had not examined whether levetiracetam has had a beneficial effect on different seizure types within epilepsy syndromes.

In conclusion, Professor Lagae explained the significance of the study, "In view of the good result in the catastrophic epilepsies, such as West syndrome and Lennox Gastaut syndrome, perhaps an early trial with levetiracetam is justified and could eventually alter the natural (downhill) course in these syndromes. Clearly, new clinical studies addressing these particular questions are needed in paediatric epilepsy. Rapid introduction is feasible and the possible positive effect of the drug can be seen early after introduction1"

It is estimated that 50 million people worldwide have epilepsy3. The mean prevalence for active epilepsy (i.e. continuing seizures or the need for treatment) is approximately 8.2 per 1,000 of the general population - although this may be higher in developing countries3.

* Levetiracetam is not registered for the treatment of epilepsy in children.

References:
1. Lagae L, Buyse G, Deconinck A, Ceulemans B. Effect of levetiracetam in refractory childhood epilepsy syndromes. Eur.J.of Paediatric Neurology, 2003, Volume 7, Number 3: 123-128
2. Glauser TA, Pellock JM, Bebin EM et al. Efficacy and safety of levetiracetam in children with partial seizures: an open label trial. Epilepsia 2002; 43: 518-524
3. WHO Factsheet number 165: Epilepsy: Etiology, Epidemiology and Prognosis. http://www.who.int/inf-fs/en/fact165.html (consultation March 20, 2003)
4. Wheless JW and Ng YT, Levetiracetam in refractory paediatric epilepsy. J.Child Neurol. 2002; 17: 413-415.


SOURCE: KETCHUM

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