Methotrexate versus Ciclosporin in the Treatment of Severe Atopic Eczema in Children: An economic evaluation

Background Eczema (also known as atopic dermatitis) affects 20% of United Kingdom children, with 16% experiencing moderate-to-severe eczema. Eczema impacts patients’ quality of life, mainly through intense itching and sleep disturbance. Most caregivers are able to control their children’s eczema with topical treatments, including emollients, topical corticosteroids or calcineurin inhibitors. For those who do not respond to these topical treatments, or who require consistent use of high potency topical corticosteroids to maintain control, systemic therapies should be considered. Ciclosporin is the most commonly used systemic treatment for paediatric patients, but methotrexate is a widely used promising alternative. Currently, there is not enough evidence to inform guidance about which treatment (methotrexate or ciclosporin) should be used to treat severe atopic eczema in children and young people. Aim In this study, we sought to compare the cost-effectiveness of two oral drug treatments (methotrexate or ciclosporin) for children and young people who have severe eczema. Methods We collected information on resource use and health-related quality of life using data from the TREAT trial. One hundred and three children and young people aged 2–16 years were randomly allocated to receive either oral methotrexate or ciclosporin for a 36-week treatment period with 24 weeks of further follow-up. An economic evaluation was undertaken, as it is currently uncertain which drug represents the best value for money for the United Kingdom National Health Service. The base case consists of a cost–utility analysis undertaken from a partial National Health Service perspective (limited to medication plus adverse event resource use for which complete data were available from clinical report forms) over 60 weeks; and multiple imputation was used to account for the missing utility data, and the analysis adjusted for baseline cost/utility/Objective Scoring Atopic Dermatitis (as appropriate), gender, age and recruiting centre. Results In the base-case analysis, usage of methotrexate resulted not only in cost savings compared to ciclosporin of −£489.67 (95% confidence interval −£685.78 to −£293.36) per participant but also in a small decrease in quality-adjusted life-years of −0.0057 (95% confidence interval −0.0384 to 0.0270) per participant; the resulting net monetary benefit at a willingness to pay per quality-adjusted life-year threshold of £20,000 (£30,000) was £375.49 (£38.45). The probability of methotrexate being cost-effective was 85.5% (73.1%) for a £20,000 (£30,000) threshold. The results were similar in unadjusted analyses and those analyses taking a wider perspective. However, in the secondary cost-effectiveness analysis, methotrexate was found to dominate ciclosporin as it was both cost saving and resulted in a greater improvement in severity scores. Limitations Both wider National Health Service resource use (collected by patient diary) and utility data had missing data, which was taken account of using multiple imputation assuming data was missing at random. Being a within-trial economic evaluation, the long-term cost-effectiveness beyond 60 weeks cannot be inferred from this data set or analysis. Conclusion and future work This study extends the findings of the TREAT trial by demonstrating that methotrexate and ciclosporin are similar in terms of costs (for visits/monitoring, adverse events and concomitant medications) and quality-adjusted life-years but that methotrexate drug costs are significantly cheaper than ciclosporin drug costs. This supports the conclusion reached in the randomised controlled trial paper that, where first-line novel systemic biologics and small molecules prescribing is generally restricted by health-funding bodies, as is the case in most jurisdictions, methotrexate provides an effective and low-cost, first-line systemic agent and is thus an alternative to ciclosporin. Given its overall cost-effectiveness, methotrexate now needs to be directly compared with novel systemic therapies. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme as award number 13/50/12, and Research for Patient Benefit (RfPB) programme, as award number PB-PG-1215-20019.