Protocol for the MERINO study: A randomized placebo-controlled trial assessing the efficacy, safety, and cost-effectiveness of methotrexate in people with erosive hand osteoarthritis

Objective: Previous studies on the efficacy of methotrexate in people with hand osteoarthritis (OA) have shown conflicting results. The MERINO trial aims to investigate the efficacy and safety of methotrexate in people with painful inflammatory erosive hand OA. Design: In total 163 participants with erosive hand OA, synovitis by ultrasound, and finger joint pain of 40-80 mm on a visual analogue scale (VAS) will be recruited from a rheumatology outpatient clinic. Participants are randomized 1:1 to receive either encapsulated oral methotrexate 20 mg/week or placebo for 12 months in a doubleblind manner. The primary endpoint is VAS finger joint pain at 6 months. Key secondary outcomes are hand function by the Australian/Canadian hand index (AUSCAN) at 6 months and radiographic progression by the Verbruggen-Veys anatomical phase scoring system at 12 months. Other secondary endpoints include hand stiffness, disease activity, health-related quality of life, grip strength, clinical joint counts, synovitis by ultrasound and MRI, bone marrow lesions by MRI, cost-effectiveness, and symptoms in knees and hips. Adverse events will be recorded. The primary analysis will be performed on full analysis set. Conclusions: The findings of this trial will be clinically relevant for patients with erosive hand OA and may influence future treatment recommendations. Clinical trial registration: EU CT number: 2023-510523-30-00, NCT04579848.