An observer blind randomised controlled trial to compare the clinical and health economic benefits of prescribing adalimuMAB instead of METHotrexate in patients with moderate psoriasis with psoriasis area and severity index (PASI) scores of =5 and <10. ( METHorMAB)

Research Question: In patients with moderate psoriasis, with psoriasis area and severity index (PASI) scores of =5 and <10, which medication, adalimumab, or methotrexate, delivers the greatest clinical and health economic benefits. Background: Psoriasis (PSO) is a chronic inflammatory skin disease affecting ~3% of the UK population. It causes significant morbidity and reduced quality of life. Traditional therapies are often not effective and have side effects. New biologic injection treatments such as adalimumab (ADA) are more effective for people with moderate-to-severe PSO (PASI =10 and DLQI >10), but PASI <10 are excluded due to lack of evidence.. Patients with moderate PSO are treated with methotrexate (MTX). PASI assesses skin redness, thickness, scaling and body surface area affected. Globally, PSO treatments are judged by the proportion of patients achieving a 75% improvement in PASI (PASI 75). All clinical trials to date, of biologic injections in psoriasis have included patients with PASI > 10. Aims and Objectives: This study will investigate the clinical effectiveness and cost-effectiveness of ADA and MTX in patients with PASI =5 and <10 who currently cannot use ADA under NHS rules. We hypothesise that in this group of patients, ADA will be superior to MTX. Patients with PSO with PASI >5 and =10 are often extremely impacted by their disease, with a PASI of 8 or 9 functionally similar to PASI 10. Work with our PPIE groups confirmed that this group of patients with moderate psoriasis has not been looked after well due to a lack of clinical trials investigating evidence for the benefit of biologic medication in the PASI >5 and =10 severity. Methods: We will conduct an assessor blind randomised controlled clinical trial comparing clinical and economic outcomes in PSO subjects randomised to ADA 40mg injections every 2 weeks or MTX 17.5mg injections weekly. The primary outcome will be the proportion of patients achieving a 75% improvement in their psoriasis area and severity score (PASI 75) at 16 weeks. The study is powered to detect a 20% difference, accepted as clinically significant by the psoriasis community, and confirmed by our PPIE consultation work. Data from 95 participants in each group would provide 90% power (two-sided significance level of 5%), to detect an odds ratio of 2.6 when comparing PASI75 at 16 weeks between the two randomisation arms (MTX and ADA). Allowing for attrition of 20%, the recruitment target is 238 in total. Secondary outcomes will include improvements in quality-of-life score, drug survival at 24 weeks and patient global assessment scores. The primary economic outcome will be the incremental cost per quality adjusted life year (QALY) gained at 24 weeks. Timelines: We will compete the study recruitment within 36 months. This includes 9 months for set up, 18 months of recruitment with 6 months follow up for all patients. The study includes an internal pilot with clear stop/go criteria. With a strong recruitment network and support from the psoriasis association, the UK Dermatology Clinical Trials Network, and the Newcastle clinical trials unit we are satisfied that this schedule is realistic and achievable. Impact: This trial will be the first to investigate the impact of a biologic drug on patients with PASI scores less than 10. If ADA is more effective than MTX, with similar or lower costs then this could lead to a meaningful change in prescribing policy for psoriasis patients within the NHS.