Methotrexate oral or subcutaneous for rheumatoid arthritis (MOOSE): study protocol for a multi-centre randomised trial

Background Rheumatoid arthritis is the commonest chronic inflammatory arthritis. Oral methotrexate is recommended as the first-line disease modifying drug for its management, and subcutaneous injections are typically prescribed if there is gastrointestinal intolerance or suboptimal efficacy. It is not known whether subcutaneous methotrexate is more effective and cost-effective compared to oral methotrexate when used as first-line treatment in people diagnosed with rheumatoid arthritis. The Methotrexate Oral Or SubcutanEous (MOOSE) trial aims to compare the clinical and cost-effectiveness of subcutaneous and oral methotrexate when used as first-line disease modifying anti-rheumatic drug in adults with rheumatoid arthritis and collect information about the acceptability of both routes of administration.

Methods MOOSE is an open-label, multi-centre, assessor-blinded, two-arm randomised controlled trial, with an internal feasibility assessment, economic evaluation and qualitative study. It is a secondary care-based trial, involving NHS hospital rheumatology clinics. Potentially eligible patients will be approached to participate around the time of their initial clinic visit. Eligible patients who consent will be randomised to either oral or subcutaneous methotrexate. Randomisation will be minimised by trial centre, 28-joint disease activity score, and disease duration. Interventions will be prescribed open-label with participants and clinicians aware of treatment allocated. Outcome assessors will be blinded to treatment allocation. Each participant will be in the trial for 52 weeks. The primary outcome is remission assessed at 24 weeks. Secondary outcomes include disease activity, quality of life, mental health and employment. A qualitative study will involve semi-structured interviews to analyse the acceptability of interventions. The health economic study will use healthcare utilisation data, quality of life data, and cost-estimates to model cost-effectiveness.

Discussion Whether to use subcutaneous or oral methotrexate first line for RA is an important question for patients and clinicians. MOOSE study will provide evidence on the clinical and cost-effectiveness of oral and subcutaneous routes of methotrexate administration to answer this important question.