Epilepsy is the most common serious neurological condition, with estimates ranging between 40-50 million active sufferers in the world today2. The mean prevalence for epilepsy (i.e. the proportion of the population with epilepsy at a given point in time) is approximately 8.2 per 1,000 of the general population2. As a result, the World Bank estimates that 1% of the total burden of disease around the world is caused by epilepsy2. However this is likely to be an underestimate due to the profound effect that epilepsy has upon the lives of individuals and their families. Epilepsy management incurs substantial direct and indirect costs on the healthcare system, the patient and their carers due to the chronic nature of the disease. Achieving seizure freedom is of paramount importance to the healthcare system, as well as to patients, because estimates of annual epilepsy related health care costs are two to seven times greater in patients with active epilepsy experiencing frequent seizures than in patients with epilepsy who are seizure free3.
A cost-effective add-on alternative to standard AED therapy
The cost-effectiveness analysis compared direct medical costs of KEPPRA add-on therapy with maintenance of standard therapy alone within the UK's National Health Service (NHS), using data derived from three pivotal randomised controlled trials 4,5,6. A one-year dose escalation decision model was set up in refractory patients who failed to respond to two or more other currently available therapies with seizure freedom being the selected effectiveness measure. This model corresponds to a realistic and representative way of treating epilepsy patients in clinical practice. Direct medical costs included costs of physician visits (both general and neurologist), accident and emergency visits, hospitalisations, Keppra drug costs as add-on and adverse events related costs. Seizure freedom and medical resource utilisation data related to seizures were derived from the pooled results of the three levetiracetam pivotal clinical trials. Expert's opinion was used to establish a likely algorithm of resources used in the UK while unit costs were taken from the Unit Costs of Health and Social Care, the British National Formulary, the Monthly index of Medical Specialties or from local audit.
In terms of effectiveness, from an hypothetical group of 1000 patients, 138 would become seizure free when using levetiracetam, compared with 7 in the controlled arm, giving an incremental effectiveness of 131 seizure free patients per year.
In terms of cost, all of the individual costs were applied to each possible outcome node, according to the amount of time spent in different phases of the model. The addition of levetiracetam would cost an average of £1595 per patient per year, compared to £900 for patients on standard therapy alone, giving an incremental cost of £695 per patient per year.
The ratio between the incremental costs and the incremental effectiveness results in an amount of £5301 per year, per seizure free patient achieved. This means that, in an hypothetical group of 1000 epileptic patients eligible for treatment with Keppra, spending an additional £695 per patient will allow 131 patients to become seizure free. The remaining 869 patients, while not becoming completely seizure free, may reasonably be expected to experience a significant decrease in their seizure frequency and severity, and hence an improvement in their quality of life. These last aspects however have not been quantified in the present study. The socio-economical value of seizure freedom is generally considered to be very high. As mentioned, the cost of general care alone are seven times higher for patients with seizures than for those where medical treatment leads to seizure freedom3.
The frequency of epilepsy surgery, and thus pre-surgical evaluation are likely to vary according to resource availability. Therefore, the effect of neuro-surgery was considered but in an alternate model.
When epilepsy surgery (investigations for neuro-surgery, neuro-surgery itself) is included in the model, adjunctive treatment with Keppra results in a cost saving of £6527 per seizure free patient per year1. Thus, when epilepsy surgery is considered in the model, the effectiveness of levetiracetam and the cost of avoided epilepsy surgeries offset the acquisition costs of Keppra.
The resounding conclusion of the study was that the substantial benefits of seizure freedom can be gained with relatively moderate costs by the addition of Keppra to standard treatment. In light of this, the high efficacy of Keppra in terms of seizure freedom combined with its cost effective use confirms its position as a potential "first-choice" add-on therapy for the treatment and management of epilepsy.
As between 20-30% of patients have refractory epilepsy that has not responded to first line anti-epileptic therapy (AED), Keppra is very important in the management of difficult to treat patients. Seizure freedom is the ultimate aim of treatment for refractory epilepsy, but is rarely achieved in add-on trials for treatment of refractory partial seizures. These economic findings add to recent clinical data that show the long-term sustained efficacy of Keppra for highly refractory patients7.
Commenting on the data, Professor Jacques Lelorier, Department of Pharmacology, University of Montreal, Canada said, "Epilepsy is a costly illness in every sense: for the individual, for the family, and it also places a major economic burden on society. For the first time, evidence shows that the incremental cost of treating patients with the modern anti-epilepsy drug (AED) Keppra is low in comparison with the benefits of seizure freedom Keppra produces and, importantly, also, in comparison with incremental cost effectiveness ratios considered as acceptable in other neurological conditions."
Professor Ley Sander, Professor of Neurology and Clinical Epilepsy at University College, London, commented, "Clinicians like myself, are already aware of levetiracetam's beneficial clinical profile and increased quality of life for some patients. Especially when you consider that about 15% of previously uncontrolled patients can become completely seizure free or experience a worthwhile reduction in seizure frequency and severity. This amount of control significantly reduces the burden of epilepsy for some patients. Indeed, when a new drug makes a patient with chronic epilepsy seizure free, it goes without saying that this is a cost-effective treatment for these patients".
Keppra is UCB Pharma's new AED, currently indicated as adjunctive therapy in the treatment of partial onset seizure with or without secondary generalisation in adults with epilepsy. Keppra was discovered and developed in UCB Pharma's research laboratories. UCB, with headquarters in Brussels (Belgium), is a pharmaceutical and chemical company, which operates on a global scale. It is committed to pharmaceuticals, as well as to technically innovative products in surface specialities for flexible films and coating resins. It employs 10,000 people around the world. The pharmaceutical research of UCB Pharma includes the following fields: respiratory, including allergy and asthma, and neurology. UCB Pharma's principle products include Zyrtec®, Xyzal® (anti-allergic), KEPPRA® (antiepileptic), Nootropil® (cerebral function regulator) and Atarax® (tranquilliser).
Please consult your national Product Information and regulatory status as they may differ from one country to the other.
*KEPPRA is a registered trademark of the UCB Group
For further information please contact:
Amanda Boswell
Ketchum London
Tel: 44-207-611-3571
Fax: 44-207-611-3850
Email:Amanda.boswell@ketchum.com
References :
- Godfroid P et al. Seizure freedom in patients treated with adjunctive levetiracetam: economic evaluation within the NHS (UK). (2003). A presentation at the American Academy of Neurology 29 March-5 April 2003, Honolulu, Hawaii, USA.
- WHO (2003) Epilepsy fact sheet 166. www.who.int/inf-fs/en/fact166.html
- Begley CE, Beghi E. The economic cost of epilepsy: a review of literature. Epilepsia 2002; 43 Suppl 4: 3-9
- Cereghino et al. Neurology 2000; 55:236-42
- Shorvon et al. Epilepsia 2000; 41:1179-86
- Ben Menachem et al. Evidence for sustained efficacy of levetiracetam as add-on epilepsy therapy. Epilepsy Research 2003, 53 (1-2): 57-64
- Boon et al. Epilepsy Research Res (2002); 48: 77-89.
Notes to editors:
- Keppra is currently indicated only as adjunctive treatment of partial onset seizures, with or without secondary generalisation, in adults with epilepsy.
- Significant clinical research with levetiracetam is ongoing, including paediatric, Primary Generalised Seizure and monotherapy trials.
- In April 2000 the USA became the first country to launch Keppra®, closely followed by Switzerland in May 2000.
- Keppra® is now available in the following countries; Argentina, Austria, Belgium, Bulgaria, Czech Republic, Denmark, Finland, France (only via hospital pharmacies), Germany, Greece, Hong-Kong, Ireland, Italy, Luxembourg, Mexico, Netherlands, Norway, Poland, Singapore, South Africa, Spain, Sweden, Switzerland, UK and USA.
- On 6 March 2003, the approval for marketing Keppra® in Canada was obtained.
- A partial seizure (I) involves just part of the brain, and can be either 'simple' (Ia) when consciousness is not affected, 'complex' (Ib) when consciousness is affected or secondary generalised (Ic) when either a simple or complex seizure spreads to involve the whole brain.
- New antiepileptic agents, like levetiracetam, first have to prove themselves as adjunctive (add-on) therapy – usually in partial seizures – before applying for approval as monotherapy.