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

Abstract

IntroductionUse 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.MethodsA 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.ResultsDuring 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0713-3) contains supplementary material, which is available to authorized users.

Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career

“…These finding are in accordance with the observation that targeting pro-inflammatory cytokines following joint injury prevents PTOA in a mouse model of the disease [32, 48, 49], like in ankylosis spondylitis [50], and rheumatoid arthritis [51, 52] . We employed IL-1Ra, via intra-articular pathway, to antagonize the main pro-inflammatory cytokine, early after acute joint trauma.…”

Incidence of hip and knee replacement in patients with rheumatoid arthritis following the introduction of biological DMARDs: an interrupted time-series analysis using nationwide Danish healthcare registers

“…Another important limitation is one inherent to all correlational studies. We acknowledge that our findings of decreased need for TKR among patients with RA could at least partly be due to increased use of treat-to-target strategies and more aggressive conventional synthetic DMARD combination therapy 36. Changes in diagnostic criteria for RA introduced in 2010 are not likely to have affected our results, but we cannot rule out that referral patterns of patients with RA to orthopaedic surgery have changed.…”

Methods for time‐varying exposure related problems in pharmacoepidemiology: An overview

“…However, a time‐varying propensity score to be added to the outcome model could be estimated to consider the variability of the data. Regression methods with time‐varying covariates or time‐varying propensity score can be used to adjust for time‐varying confounders only in the scenario that the time‐varying confounders are not affected by previous levels of the exposure, ie, they are not intermediates between the exposure and the outcome. In the most common scenario where the time‐varying confounder is also an intermediate between exposure and outcome, both regression with time‐varying covariates or time‐varying propensity score methods provide biased estimates .…”