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

Moura CS, Abrahamowicz M, Beauchamp ME, Lacaille D, Wang Y, Boire G, Fortin PR, Bessette L, Bombardier C, Widdifield J, Hanly JG, Feldman D, Maksymowych W, Peschken C, Barnabe C, Edworthy S, Bernatsky S, CAN-A - Arthritis Res. Ther. (2015)

Bottom Line: The outcome was defined using procedure codes submitted by orthopedic surgeons.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. cristiano.soaresdemoura@mail.mcgill.ca.

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.

No MeSH data available.


Related in: MedlinePlus

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)
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Fig1: 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)

Mentions: Among the alternative measures of drug exposure, the best-fitting multivariable Cox model relied on the cumulative duration of drug use in the first year after cohort entry (Table 2). Joint replacement throughout follow up was significantly lower for patients with higher cumulative duration of either MTX (HR = 0.95 per month of use, 95 % CI 0.93, 0.97) or of other DMARDs (HR = 0.97 per month of use, 95 % CI 0.95, 0.99) within the first year after cohort entry. These results can respectively be translated into a 5 % decrease in the hazard of surgery associated with every additional month of early MTX use in the first year of follow up, and a 3 % decrease in the hazard of surgery for every additional cumulative month of early use of other DMARDs. These associations became much stronger with prolonged use of the relevant drugs in the first year. For example, the early use of MTX or other DMARDs for 6 months was associated with 31 % (HR = 0.69, 95 % CI 0.59, 0.80) and 27 % (HR = 0.83 95 % CI 0.73, 0.95) reduction in the hazard of joint replacement surgery during follow up. To facilitate assessment of the impact of early treatment with MTX and/or other DMARDs, Fig. 1 compares the Kaplan-Meier-like curves, for the proportions of patients who remain free of joint replacement in four subgroups, defined based on treatment(s) received during the first year after the cohort entry: 1) users of MTX only (Metho_only); 2) users of other DMARDs only (DMARDs_only); 3) users of both MTX and DMARDs (Metho_DMARDs); and 4) patients not prescribed either MTX or any other DMARDs during the first year of follow up (None). It is evident that patients treated with MTX and/or other DMARDs in the first year have lower long-term risks of requiring joint replacement, with cumulative risk during the first 4–8 years of follow up lower by about 2 % (Fig. 1). For example, after about 6 years (2,000 days) the cumulative risk is about 5 % in those treated versus about 7 % in those not treated in the first year.Table 2


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

Moura CS, Abrahamowicz M, Beauchamp ME, Lacaille D, Wang Y, Boire G, Fortin PR, Bessette L, Bombardier C, Widdifield J, Hanly JG, Feldman D, Maksymowych W, Peschken C, Barnabe C, Edworthy S, Bernatsky S, CAN-A - Arthritis Res. Ther. (2015)

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)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522999&req=5

Fig1: 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)
Mentions: Among the alternative measures of drug exposure, the best-fitting multivariable Cox model relied on the cumulative duration of drug use in the first year after cohort entry (Table 2). Joint replacement throughout follow up was significantly lower for patients with higher cumulative duration of either MTX (HR = 0.95 per month of use, 95 % CI 0.93, 0.97) or of other DMARDs (HR = 0.97 per month of use, 95 % CI 0.95, 0.99) within the first year after cohort entry. These results can respectively be translated into a 5 % decrease in the hazard of surgery associated with every additional month of early MTX use in the first year of follow up, and a 3 % decrease in the hazard of surgery for every additional cumulative month of early use of other DMARDs. These associations became much stronger with prolonged use of the relevant drugs in the first year. For example, the early use of MTX or other DMARDs for 6 months was associated with 31 % (HR = 0.69, 95 % CI 0.59, 0.80) and 27 % (HR = 0.83 95 % CI 0.73, 0.95) reduction in the hazard of joint replacement surgery during follow up. To facilitate assessment of the impact of early treatment with MTX and/or other DMARDs, Fig. 1 compares the Kaplan-Meier-like curves, for the proportions of patients who remain free of joint replacement in four subgroups, defined based on treatment(s) received during the first year after the cohort entry: 1) users of MTX only (Metho_only); 2) users of other DMARDs only (DMARDs_only); 3) users of both MTX and DMARDs (Metho_DMARDs); and 4) patients not prescribed either MTX or any other DMARDs during the first year of follow up (None). It is evident that patients treated with MTX and/or other DMARDs in the first year have lower long-term risks of requiring joint replacement, with cumulative risk during the first 4–8 years of follow up lower by about 2 % (Fig. 1). For example, after about 6 years (2,000 days) the cumulative risk is about 5 % in those treated versus about 7 % in those not treated in the first year.Table 2

Bottom Line: The outcome was defined using procedure codes submitted by orthopedic surgeons.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. cristiano.soaresdemoura@mail.mcgill.ca.

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.

No MeSH data available.


Related in: MedlinePlus