Early Use of DMARDs Linked to Delayed Need for Joint Replacement Surgery

Study results suggest that longer exposure to methotrexate and other disease-modifying anti-rheumatic drugs within the first year of diagnosis is associated with a significantly longer time to joint replacement surgery.

Rheumatologists are very familiar with the severe damage that untreated rheumatoid arthritis (RA) can do, including joint deformity, disability, loss of physical function and significantly reduced quality of life. Of course, RA patients have a lot more help for successfully managing their condition today than they did just a few years ago, with new disease-modifying anti-rheumatic drugs (DMARDs) and new biologics that are effective and well-tolerated in most patients.

New information published in Arthritis Research & Therapy offers some additional encouraging news. It has long been clear that earlier treatment increases the chances of clinical response and disease remission, and population-based studies have demonstrated that orthopedic surgery rates have declined alongside the concomitant increase in anti-rheumatic drug use. This latest study suggests that longer exposure to RA stalwart methotrexate (MTX) and other DMARDs within the first year of diagnosis is associated with a significantly longer time to joint replacement surgery. The study authors note, “…prompt initiation of therapy and better control of disease could ultimately decrease the long-term need for orthopedic surgery.”

The study reviewed a population-based RA cohort assembled from health administrative databases in Quebec, using the Quebec Health Insurance Program databases from 2002—2011. The data include hospitalization discharge diagnoses and physician-visit billing-claim diagnostic codes. The authors used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows 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 agents, other biologics, cyclooxygenase-2 inhibitors, nonselective nonsteroidal antiinflammatory drugs, and systemic steroids), and markers of disease severity.

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. This finding is consistent with other studies suggesting that early use of DMARDs results in both short-term and long-term benefits.

One major caveat to the study is that among the cohort members with incident RA, about a quarter of generally older, co-morbid individuals did not receive any DMARD therapy during the follow-up time (median of 4.5 years). “This combination of increased age and comorbidity may represent a relative contraindication to DMARD use in this subgroup. Conversely, they may represent a subgroup with milder disease,” the study authors note. “This subset of individuals not receiving MTX or other DMARDs, being at high risk of requiring future joint surgery for OA, could explain part of the observed potentially protective effect of cumulative MTX and other DMARD use in the first year of cohort entry.”

The researchers also noted that time until joint replacement is influenced not only by necessity, but also by healthcare access. “For example, individuals with higher socioeconomic status tend to have better access to care, and thus, have shorter waiting times even within publicly funded healthcare systems, to receive elective surgery.” For that reason, the study authors did adjust for variables related to socioeconomic status, such as being on social assistance, and ecological measures such as family income, employment, and education.