Epilepsy, a chronic neurological disorder has an estimated prevalence of between 0.4% and 1.0% globally, and 1% in South Africa. Epilepsy has multiple underlying causes including head injuries, vascular insults, hippocampal sclerosis, cortical dysgenesis, drug or alcohol abuse and infectious diseases, such as neurocysticercosis and HIV/AIDS. Causes in South Africa are likely to be infectious due to the high HIV and tuberculosis prevalence. The condition has substantial individual and societal economic impacts, with economic costs ranging from the direct and indirect costs of treatment and loss of productivity due to illness. Primary treatment of epilepsy in the South African public sector is through pharmacotherapy, with monotherapy being preferred to polytherapy. No cost-effectiveness studies on the first-line treatment of epilepsy have been conducted in the South African context or in similar contexts using the combination of drugs in this analysis which are levetiracetam, lamotrigine, carbamazepine, phenytoin and valproate. The current first-line epilepsy treatment in South Africa is lamotrigine, phenytoin or carbamazepine. Levetiracetam is under consideration for use as a first-line treatment due to the reported minimal serious side effects, its ease of use, linear pharmacokinetics and reduced interaction with other drugs. The study was model-based and conducted from the providers’ perspective, specifically in the South African public health sector. It compared levetiracetam, lamotrigine, carbamazepine, phenytoin and valproate as first-line treatment in focal seizures (International Classification of Diseases (ICD)-10 code: G40.2) and generalized tonic-clonic seizures (ICD-10 code: G40.3). The population considered for the analysis was patients with newly diagnosed epilepsy expected to utilize services in the public health sector. The analysis consisted of a costeffectiveness analysis and a budget impact analysis. The budget impact analysis was conducted for the first year of treatment for each of the treatment strategies, while the cost-effectiveness analysis was conducted for a five-year period. Both a decision-tree representing the first six months of treatment and a Markov model representing the rest of the treatment period were used for the cost-effectiveness analysis. The methodology for the cost-effectiveness analysis was based on the International Decision Support Initiative (IDSI) reference case. Costs were expressed as South African Rands, 2018 value and effects were expressed as Quality Adjusted Life Years (QALYs). Results were expressed as Incremental Cost-Effectiveness Ratios (ICERs) and sensitivity analyses were performed to cater for uncertainty. The use of levetiracetam along with the use of phenytoin, valproate and carbamazepine in the treatment of newly diagnosed epilepsy was found to be dominated by treatment using lamotrigine. Treatment with lamotrigine over a five-year period was found to be the least costly option and had the highest number of QALYs gained. The estimated cost of treating one case of epilepsy was R1 252 higher using levetiracetam compared to using lamotrigine. Levetiracetam had 0,02 QALYs lower than those of lamotrigine. Phenytoin, carbamazepine and valproate were found to have the same effect size of 3,97 QALYs. Sensitivity analyses were conducted using some levetiracetam-related costs and quality of life values. Both the levetiracetam-related costs used in the sensitivity analyses showed that lower cost values were associated with less negative ICER values (i.e. levetiracetam became comparatively more cost-effective as the levetiracetam-related costs became lower). There were no trends observed regarding the impact of the quality of life measures and the probability of remaining controlled on levetiracetam on the ICER values obtained. The pharmaceutical costs of treating newly diagnosed epilepsy with levetiracetam were found to be higher in comparison to those of comparators. For a 100% treatment coverage, the cost of treatment with lamotrigine, the other second-generation AED under analysis was about R19 million cheaper compared to treatment with levetiracetam over a one-year period. Treatment with carbamazepine was found to be the cheapest option, costing about R20 million less than treatment with levetiracetam. On inclusion of other health systems costs associated with seizure and side-effect treatment levetiracetam was still found to be the costliest treatment option while lamotrigine became the least costly option. The effect sizes of all the treatments under analysis were similar, with a difference of 0,04 QALYs being observed between the most effective and the least effective treatment option. This led to costs being the main driver of the resulting ICER values. Approximately a 93% price reduction is required for levetiracetam to be more cost-effective than lamotrigine. The model results for the cost-effectiveness analysis agree with the findings from the study conducted to inform the National Institute for Health and Clinical Excellence (NICE) treatment guidelines in the United Kingdom, which found that levetiracetam was not cost-effective. Lamotrigine is recommended for the treatment of both partial and generalized tonic-clonic seizures by the Health Technology Assessment Agencies in the United Kingdom and Scotland. It is the only drug recommended for the treatment of both indications, with carbamazepine being recommended for the treatment of partial seizures and valproate for the treatment of generalized tonic-clonic seizures. Levetiracetam was found to not be a cost-effective treatment option for both generalized tonicclonic seizures and partial seizures in the South African public health sector context, even when accounting for the titration period and the drug prevalence of Steven Johnson Syndrome associated with some of the comparators. Lamotrigine is therefore recommended for use as the first-line treatment of epilepsy in the South African public health sector.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uct/oai:localhost:11427/31720 |
| Date | 30 April 2020 |
| Creators | Chanakira, Esther Z |
| Contributors | Mafunda, Vimbayi, Wilkinson, Tommy |
| Publisher | Faculty of Health Sciences, Health Economics Unit |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Master Thesis, Masters, MPH |
| Format | application/pdf |
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