Does different administration method of methotrexate matter in early rheumatoid arthritis? An exploratory register-based study.

Objectives: We aimed to study the course of disease activity and pain over two years in patients with early rheumatoid arthritis who began subcutaneous (SC) or peroral (PO) methotrexate (MTX) as part of their first treatment strategy. Treatment failures and drug survival were analysed.

Methods: Patients who received a new reimbursement for RA between 1.1.2016 to 31.12.2023 were identified in the Reimbursement Register; purchases of DMARDs were available in the Drug Purchase Register. Clinical and demographic data were extracted from the Finnish Rheumatology Quality Register. Locally estimated scatterplot smoothing (LOESS) trajectories were used to illustrate the development of disease activity and pain for two years. Treatment failures, defined as the probability to avoid bDMARDs, were analysed with Cox regression, adjusted for age and sex. The proportion of patients taking MTX at two years were calculated.

Results: From the database, we identified 4,655 patients (mean age 60 years, 64% female, 80% seropositive) who started MTX as part of the initial medication for early RA. MTX SC was purchased by 1076(23.1%) and MTX PO by 3579(76.9%) patients. At baseline, the mean (SD) DAS28 was 3.8(1.2) for MTX SC starters and 3.9(1.2) for MTX PO starters. The trajectories for disease activity and pain were more favourable for two years in patients with initial MTX SC versus PO. The probability (95%CI) to avoid bDMARDs was 0.87(0.85 to 0.89) for MTX SC and 0.91(0.90 to 0.92) for MTX PO starters (p<0.001). At two years, MTX was purchased by 80% and 79% of patients who started with MTX SC versus PO, respectively.

Conclusions: Our study provides real-world evidence of the use MTX SC and PO as part of the first treatment strategy for RA. Starting with MTX, SC may be more favourable for patients, in terms of disease activity and pain, over the following two years.