Article Text

FRI0684 Early treatment with methotrexate improves all-cause and cardiovascular survival among an inception cohort of seniors with rheumatoid arthritis
  1. J Widdifield1,
  2. JM Paterson2,
  3. A Huang2,
  4. S Bernatsky1,
  5. on behalf of CANAIM
  1. 1Mcgill University, Montreal
  2. 2Institute for Clinical Evaluative Sciences, Toronto, Canada


Background We previously observed that incident RA patients have an increased risk of all-cause and cardiovascular disease (CVD) mortality relative to the general population in Ontario.1

Objectives To evaluate the effect of treatment and other factors on all-cause and CVD mortality among incident senior RA patients.

Methods We studied incident RA patients within the population-based Ontario Rheumatoid Arthritis Database (ORAD) who were diagnosed after their 65th birthdate (ensuring comprehensive drug coverage) between 2000 and 2013. Patients are included in ORAD if they received 3 physician billing RA diagnosis codes (with at least one provided by a MSK specialist) over 2 yrs OR at least 1 hospital RA diagnosis code. All patients were followed from cohort entry (when all case definition criteria were met) until death, out-migration, or end of study period (Dec 2013). Two multivariable Cox regression models were performed to estimate hazard ratios (HRs) for each outcome (all-cause and CVD mortality, separately), exploring the effects of both baseline/early treatment (within the year preceding index date) and time-varying medication exposures over the entire duration of follow-up (for methotrexate, other DMARDs, anti-TNFs, COXIBS, NSAIDs, glucocorticosteroids, statins, antihypertensives), baseline comorbidities (within 3 yrs prior to index date), time-varying development of extra-articular manifestations (as proxy for disease severity), healthcare use, and demographics (age, sex, rurality, SES).

Results 28,172 incident RA patients were followed for 141,072 person years. During follow-up, 8,848 (31%) patients died with 1,419 (5%) deaths due to CVD, corresponding to an all-cause rate of 62.7 deaths (95% CI 61.4,64.0), and 10.1 deaths due to CVD (95% CI 9.5,10.6) per 1,000 patient-years, respectively. In our multivariable analysis focused on all-cause mortality, early treatment with methotrexate [HR 0.90 (95% CI 0.85,0.96)] and other DMARDs [HR 0.92 (95% CI 0.87,0.97)] were associated with a lower mortality risk. For CVD mortality, early treatment with methotrexate was associated with lower risk estimates [HR 0.71 (95% CI 0.60,0.83)], which was not clearly seen with other DMARDs [HR 0.94 (95% CI 0.82, 1.08)]. Use of COX-II inhibitors and NSAIDs at baseline were associated with lower HR for all-cause and CVD mortality risk, though we were unable to detect clear associations with greater use during follow-up. Greater cumulative exposure to glucocorticosteroids, comorbidities, and extra-articular manifestations of RA were associated with increasing risk of all-cause and CVD mortality.

Conclusions Patients with early exposure to methotrexate had a lower risk of all-cause and CVD mortality. Our findings support the hypothesis that early treatment, by reducing inflammation, may help improve survival in RA. However, residual confounding cannot be ruled out.


  1. Widdifield J, et al. Risk of Vascular Mortality in Seniors with New-Onset Rheumatoid Arthritis. Arthritis Rheumatol 2016; 68 (suppl 10).


Disclosure of Interest None declared

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