Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study

Abstract

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.

Fig. 1

Kaplan-Meier estimates of time to joint replacement surgery. Groups of drug exposure were based on treatment(s) received during the first year after the cohort entry: 1) users of methotrexate (MTX) only (Metho_only); 2) users of other disease-modifying anti-rheumatic drugs (DMARD) only (DMARDs_only); 3) users of both MTX and DMARDs (Metho_DMARDs); and 4) patients not prescribed either MTX or any other DMARD during the first year of follow up (None)