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Published on: May 16, 2025
Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large
Cristiano S Moura1,2, Michal Abrahamowicz3,4, Marie-Eve Beauchamp5
1Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. cristiano.soaresdemoura@mail.mcgill.ca.
Introduction:
Use of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada.
Methods:
A cohort of new-onset RA patients was identified from Quebec's physician billing and hospitalization databases from 2002-2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity.
Results:
During follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95% confidence interval, 95% CI 0.93-0.97) or other DMARDs (HR = 0.97, 95% CI 0.95-0.99) was associated with longer time to joint replacement.
Conclusions:
Our results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.
Insights
Early use of disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA) is linked to delayed joint replacement surgery. Increased exposure to methotrexate (MTX) or other DMARDs within the first year of diagnosis shows a protective effect.
Area of Science:
- Rheumatology
- Clinical Epidemiology
- Pharmacoeconomics
Background:
- Rheumatoid arthritis (RA) management aims to prevent joint damage and reduce the need for joint replacement surgery.
- Disease-modifying anti-rheumatic drugs (DMARDs) are central to RA treatment strategies.
- The association between early RA drug utilization and long-term surgical outcomes requires further investigation.
Purpose of the Study:
- To evaluate the relationship between the use of disease-modifying anti-rheumatic drugs (DMARDs) and the occurrence of joint replacement surgery in rheumatoid arthritis (RA) patients.
- To determine if the timing and cumulative exposure to specific DMARDs influence the risk of requiring joint replacement.
Main Methods:
- A retrospective cohort study of new-onset RA patients in Quebec (2002-2011) using physician billing, hospitalization, and pharmacy databases.
- Cox regression models with time-dependent variables assessed cumulative DMARD exposure, focusing on the first year post-diagnosis.
- Adjustments were made for sociodemographics, comorbidities, prior healthcare utilization, and other concomitant medications.
Main Results:
- Among 11,333 RA patients, 608 underwent joint replacement surgery over a median of 4.6 years.
- Cumulative exposure to methotrexate (MTX) or other DMARDs within the first year of RA diagnosis was associated with a reduced hazard of joint replacement.
- A 1-month increase in early MTX exposure (HR 0.95) or other DMARDs (HR 0.97) correlated with a longer time to surgery.
Conclusions:
- Extended exposure to methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs) within the initial year of rheumatoid arthritis (RA) diagnosis is associated with a delayed need for joint replacement surgery.
- These findings underscore the importance of early and sustained DMARD therapy in RA management to preserve joint function and potentially avert surgical intervention.
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