Title: Methotrexate versus Ciclosporin in the Treatment of Severe Atopic Eczema in Children: An economic evaluation
Funder: Department of Health and Social Care

Abstract: Background: Eczema is an inflammatory skin condition leading to inflamed, intensely itchy skin. Around 20% of UK children experience eczema, of whom 16% experience moderate to severe forms [2]. Eczema has a similar impact on health-related quality-of-life in children as other common conditions such as asthma and diabetes [3]. Eczema has been estimated to have similar cost implications to asthma (~&pound;500 million per annum) [4]. Treatment options for severe child eczema are limited, and there are considerable concerns about short- and long-term side-effects [5]. The TREatment of severe atopic eczema in children Taskforce (TREAT) survey of 765 consultant dermatologists, paediatricians, and allergists concluded that ciclosporin was the preferred treatment despite significant risks of nephrotoxicity and hypertension with long-term use [6], and eczema frequently reoccurring post-treatment [7]. This contrasts with recent evidence in relation to Methotrexate which suggests it is more effective and has a better safety profile [8-9]. Hence there is considerable uncertainty as to the preferred treatment option. Further, methotrexate may be more cost-effective: drug costs for a 36 week treatment course for a 50kg child are up to 53 times cheaper with methotrexate than circlosporin. Further savings may also result from reductions in side-effects and flares. Aim: To increase the value of a recently funded trial comparing two drugs for severe child eczema (TREAT trial, http://www.nets.nihr.ac.uk/projects/eme/135012) by conducting an add-on economic evaluation which aims to: 1. Estimate resource use and costs in severe child eczema in the methotrexate arm compared to the ciclosporin arm; 2. Estimate Quality-Adjusted Life Years (QALYs) in each arm; 3. Undertake a cost-effectiveness and cost-utility analysis to assess which treatment represents the best value-for-money for NHS provision. 4. Estimate uncertainty levels associated with the decision about treatment provision. Methods: This add-on study will use recommended methods [10-12] to undertake an economic evaluation alongside the TREAT trial which is evaluating treatments of severe recalcitrant atopic eczema in 102 children aged 2-16 years. &emsp; Data collection: Resource use associated with both treatment options (drug use, monitoring and adverse events) will be recorded during the 36-week treatment period. Wider resource use (primary care visits, prescriptions, other health contacts) will be regularly recorded in study diaries completed by parents or participants (where deemed able) at baseline until week 60. Generic health-related quality-of-life will be measured using the CHU-9D (Child Health Utility-9-dimensions): completed by children aged 7-16 and parental proxies otherwise at baseline, 12, 36, 48 and 60 weeks. O-SCORAD score at 12 weeks will measure eczema severity and the number of reflares at 24 weeks will also be noted. Analysis: Costs will be estimated from the perspective of the NHS and Personal Social Services [13], by attaching published unit costs [14-16]. The utility score from the CHU-9D [17] will be used to estimate QALYs for the trial period using linear interpolation and area-under-the-curve analysis adjusting for baseline differences. The economic evaluation will estimate the mean incremental cost and mean incremental effect of methotrexate compared to ciclosporin (separate mean incremental effects will be estimated for: CHU-9D (QALY gain); change in o-SCORAD; and flare number). A regression-based approach (for instance seemingly-unrelated regression equations if assumptions are met, [18]) will be used to estimate the mean incremental cost and effects. Bootstrapping will explore uncertainty levels associated with the decision to adopt either treatment through the estimation of cost-effectiveness acceptability curves [19]. Research contribution: Funding this work will enable the first economic evaluation to be undertaken comparing these treatments for severe child eczema. This will improve patient benefit by providing evidence for the most cost-effective treatment of severe child eczema: using the most cost-effective treatments ensures value-for-money is achieved from NHS funds.

Lay abstract: The funds available to provide health care are limited, so choices have to be taken about which treatments to provide. These decisions should be informed using evidence about value for money, which can be estimated through an economic evaluation (also known as cost effectiveness analysis) to compare the costs and benefits of alternative treatments. The National Institute of Health and Care Excellence (NICE) does not currently have enough evidence to make a recommendation about which treatment should be used to treat severe eczema in children. Eczema affects 20% of children in the UK. The impact on patients quality of life, mainly through intense itching and sleep disturbance, and the economic burden (around &pound;500 million per annum) is comparable to asthma in children. In this study we seek to compare the cost effectiveness of two drug treatments for children who have severe eczema. We will do this by collecting information on resource use and health-related quality-of-life using data from a recently funded research study (the TREAT trial). 102 children aged 2 to 16 years will be randomly chosen to be given either Ciclosporin or Methotrexate for a 36 week treatment period with 24 weeks further follow-up. An economic evaluation is required, as it is currently uncertain which drug represents best value-for-money for the UK National Health Service (NHS). One treatment could be more effective but not cost effective. This study addresses one of the treatment uncertainties identified by a James Lind Alliance group of patients, carers and health professionals: &ldquo;What is the best and safest way of using drugs that suppress the immune system when treating eczema?&rdquo;. It will also help inform future revision of the NICE management guidelines for childhood eczema. This study will lead to patient benefit by identifying the drug which offers best value-for-money for the NHS.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: SKIN