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Economic evaluation of levetiracetam as an add-on therapy in patients with refractory epilepsy

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Abstract

Objectives: This study provides the results of a cost-effectiveness analysis of levetiracetam as an adjunctive treatment for refractory epilepsy from the Canadian Ministry of Health perspective. The main objective is to estimate the expected cost-effectiveness ratio expressed as the incremental cost per seizure-free day gained when using levetiracetam. In addition, this study examines the potential savings that might result by reducing the number of surgical evaluations and surgery when using levetiracetam.

Methods: A 1-year dose escalation decision-tree model comparing levetiracetam plus standard therapy with standard therapy alone was designed in order to combine probability, resource use and unit cost data (1999 Canadian dollars [$Can]). The short-term outcomes were derived from three phase III randomised, double-blind, placebo-controlled trials performed in 904 patients, aged 16–70 years, with at least 1 year history of epilepsy, two to four partial seizures per month, and receiving a maximum of two classic antiepileptic drugs.

Results: The average gain in seizure-free days attributed to levetiracetam was 19 days per patient per year and the incremental cost-effectiveness ratio (ICER) for levetiracetam add-on in the base-case scenario was $Can80.7 per seizure-free day gained per patient per year. Moreover, when surgical investigation and surgery are considered in the model, the use of levetiracetam may be dominant, with substantial savings to the overall healthcare budget. All univariate sensitivity analyses show that the model was robust to the assumptions made.

Conclusions: The economic analysis presented in this paper suggests, given a wide range of assumptions, that the increased cost of treating patients (with refractory epilepsy) with levetiracetam may be partially offset by a reduction in other direct medical costs (from the Canadian Ministry of Health perspective), as a consequence of an increase in the number of seizure-free days. Moreover, potential cost savings may be foreseen when it is assumed that levetiracetam may reduce the number of candidates for surgical evaluation and surgery through a reduction of seizure frequency.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

Philippe Godfroid is an employee of UCB Pharma SA. The authors have no other conflicts of interest directly relevant to this study. All authors played an equal role in the conducting of different phases of the economic model (scientific construction, checking accuracy of data inputs, writing of the reports, etc.). The Scientific Advisory Board was responsible for ensuring the model was a good proxy for daily clinical practice. The study was funded by UCB Pharma, Braine-l‘Alleud, Belgium.

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Authors and Affiliations

  1. Research Centre, University of Montreal Hospital, Montreal, Québec, Canada

    Lucie Blais, Odile Sheehy, Jean-Marc Saint-Hilaire, Gilles-Pierre Bernier & Jacques LeLorier

  2. Health Outcomes Research Unit, R&D, UCB Pharma, Braine-l’Alleud, Belgium

    Philippe Godfroid

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  1. Lucie Blais
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Appendices

Appendices

Appendix I: Members of the Scientific Advisory Board

Richard Desbiens, Département des Sciences Neurologiques, Université Laval, Pavillon Enfant-Jésus, Québec, Canada

Pierre Langevin, Centre Hospitalier de l’Université Laval, Pediatric Neurology, Sainte-Foy, Québec, Canada

Jack Schneiderman, St Michael’s Hospital, Wellesley Central Site, Toronto, Ontario, Canada

Samuel Wiebe, London Health Sciences Center University Campus, London, Ontario, Canada

Appendix II: Algorithm Used to Cost Adverse Events

Adverse events reported in the levetiracetam clinical trials are given in the US prescribing information.[17–19,22] The SAB reviewed and endorsed all assumptions. Costing was based on official sources.[16]

Somnolence and Asthenia

The SAB assumed 80% of cases will require a neurologist visit at a cost of $Can105.40 per visit.

Headache

The SAB assumed 100% of patients with headache will take acetaminophen (paracetamol) [Tylenol®, cost of 24 caps $Can2.57] and 80% will have a consultation with their neurologist ($Can105.40 per visit).

Infection (Common Cold)

The SAB assumed 100% of the patients with a common cold will take paracetamol (acetaminophen) [Tylenol®, cost of 24 caps $Can2057] and 25% will have a consultation with a general practitioner ($Can51.40 per visit).

Flu Syndrome

The SAB assumed 100% of the patients with flu syndrome will take paracetamol (acetaminophen) [Tylenol®, cost of 24 caps $Can2057] and have a consultation with a general practitioner ($Can51.40 per visit); 50% will have a prescription for an antibacterial (cost $Can42.00).

Dizziness

The SAB assumed 80% will have a consultation with a neurologist ($Can105.40 per visit).

Pharyngitis

The SAB assumed 25% will have a consultation with a general practitioner ($Can51.40 per visits) and 100% of them will have a prescription for an antibacterial (cost $Can42.00).

Rhinitis

The SAB assumed no medical consultation and that all patients would take Tylenol® sinus ($Can3.77 for 12 caps).

Accidental Injury

The SAB assumed:

  • 89.5% of patients will have a visit to the emergency room ($Can70.62 general practitioner consultation in emergency room) and an x-ray ($Can62.50 + $Can62.50 supplies).

  • 10% will use an ambulance ($Can245.00).

  • 8% will have a visit to the emergency room, an x-ray and an average of five stitches (3cm) [$Can59.38 for five stitches].

  • 1% will have a visit to the emergency room, an x-ray and a fracture ($Can154.38 for a fracture).

  • 1% will have a visit to the emergency room, an x-ray and have shock (the patient will stay 24 hours at the emergency room under observation).

  • 0.5% will have a visit to the emergency room, an x-ray and hospitalisation for 3 days ($Can1195.48 per day).

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Blais, L., Sheehy, O., Saint-Hilaire, JM. et al. Economic evaluation of levetiracetam as an add-on therapy in patients with refractory epilepsy. Pharmacoeconomics 23, 493–503 (2005). https://doi.org/10.2165/00019053-200523050-00008

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