The MOOSE study: a trial to compare whether methotrexate injections are better at controlling rheumatoid arthritis, have less side effects and are more cost-effective than oral methotrexate tablets

INTERVENTION: The MOOSE trial aims to compare the clinical and cost‐effectiveness of subcutaneous and oral methotrexate in adults with rheumatoid arthritis (RA) and to collect information about the acceptability of both routes of methotrexate administration. Intervention The intervention is methotrexate, administered by subcutaneous injection. Starting dose will be in the range of 7.5 to 15 mg/week, with 4‐weekly dose escalation, not to exceed 25 mg/week. A higher or lower starting dose will be permitted if this was the usual practice of the patient’s rheumatologist. Comparator The comparator is oral methotrexate, administered in tablet form. Starting dose will be in the range of 7.5 to 15 mg/week, with 4‐weekly dose escalation, not to exceed 25 mg/week. A two‐ or three‐weekly dose escalation will be permitted if this was the usual practice of the patient’s rheumatologist. Randomisation Patients with newly diagnosed RA, who have not previously been treated with methotrexate, have consented to take part in MOOSE, and meet the eligibility criteria, will be randomised to either subcutaneous or oral methotrexate. Treatment will be assigned randomly using a minimisation algorithm balancing by trial recruiting centre, DAS‐28‐CRP (<5.1 and =5.1) and disease duration (<4 months, 4‐12 months, and >12 months). Allocation will be concealed using a web‐based randomisation system developed and maintained by the Nottingham Clinical Trials Unit (NCTU). Follow‐up The treatment period is 52 weeks from randomisation to the end of follow‐up. Allocated treatment for both arms may be stopped or changed at any point during the follow‐up period, on the guidance of the participant s rheumatologist. In both arms of the trial, participants will have the same follow‐up schedule. Screening visit During t CONDITION: Rheumatoid arthritis ; Musculoskeletal Diseases PRIMARY OUTCOME: Remission of rheumatoid arthritis (RA), defined as DAS‐28‐CRP <2.6, at 24 weeks SECONDARY OUTCOME: The following endpoint evaluations will coincide with clinic visits and questionnaires completed at 4, 8 12, 24 and 52 weeks after commencing the trial and starting methotrexate treatment:; 1. Remission of rheumatoid arthritis (RA) at 12 and 52 weeks, defined as DAS‐28‐CRP <2.6; 2. Remission of RA at 12, 24 and 52 weeks, as per 2022 Boolean American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) definition, Simplified Disease Activity Index; 3. Disease activity at 12, 24 and 52 weeks, defined as DAS‐28‐CRP, Clinical Disease Activity Index, Simplified Disease Activity Inde Xand components of these scores; 4. Response to treatment at 12, 24 and 52 weeks, defined as DAS‐28‐CRP; EULAR and ACR 20, 50, 70 responses; 5. Function measured using HAQ‐DI at 12, 24 and 52 weeks; 6. Quality of life, fatigue, anxiety, and depression measured using RA‐QoL, FACIT‐F, GAD‐7, PHQ‐8, and EQ‐5D‐5L at weeks 24 and 52; 7. Work productivity and employment measured using WPAI at 24 and 52 weeks; 8. Cost‐effectiveness of subcutaneous over oral methotrexate measured using service utilisation at week 52; 9. Treatment acceptability assessed using qualitative interviews, BMQ and TFAQ at 4‐8 weeks and 24‐32 weeks INCLUSION CRITERIA: 1. Age =18 years 2. Meets American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA 3. Active RA defined as at least one swollen joint assessed by a rheumatologist 4. Willing to initiate methotrexate 5. RA not treated with methotrexate previously 6. Disease Activity Score 28‐joints including C reactive protein (DAS‐28‐CRP) =2.6 (blood test from initial clinic visit to be used to calculate this score at baseline visit)