Background Patients with rheumatoid arthritis (RA) have an increased mortality compared with the general population.1 Established risk factors for premature mortality include active inflammation/disease activity, comorbidity and extra-articular disease manifestations. Thus, early and greater exposure to disease-modifying anti-rheumatic drugs (DMARDs) may mitigate these risk factors and improve survival in RA.
Objectives Our aim was to evaluate the associations between RA drug exposures and survival in seniors with incident RA.
Methods This retrospective cohort study investigated all incident cases of RA diagnosed from 2000 to 2013. We studied a subset of patients within the Ontario RA Database (ORAD) - a validated population-based cohort of all Ontarians with RA - who were aged 66 years and older who have comprehensive public drug insurance. We used Cox proportional hazards regression to investigate mortality, defined as death from any cause, exploring time-dependent cumulative drug exposures during the entire duration of follow-up, while adjusting for baseline age, sex, urban vs. rural residence, socioeconomic status, pre-existing comorbidities (e.g. hypertension, COPD, diabetes, coronary artery disease, cancer), past drug exposures, time-dependent number of physician visits, and extra-articular manifestations of RA (as proxies for RA severity). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated.
Results Among 25,416 senior RA patients, 67.8% were female, the mean (SD) age was 75.2 (6.5) years, and 85.4% lived in urban areas. During median and maximum follow-up times of 4.4 and 13.2 years, respectively, 7,956 patients died (31.3%) for a mortality rate of 6.2 per 100 person-years. In multivariable analyses, we observed no association between greater cumulative exposure to methotrexate, other DMARDs, or anti-TNF agents and survival. Greater exposure to corticosteroids was associated with greater risk of mortality [HR 1.15 (95% CI 1.14-1.17)], as were greater baseline comorbidity [Charlson HR 1.36 (95% CI 1.34-1.38)] and extra articular disease [HR 1.53 (95% CI 1.47, 1.61)]. Females and residents living in urban areas had lower mortality risk [HR 0.78 (95% CI 0.75-0.82) and HR 0.92 (95% CI 0.86-0.98), respectively].
Conclusions Though we could not demonstrate an association between exposure to DMARDs and over-all survival in seniors with RA, cause-specific mortality warrants further investigation. Greater exposure to corticosteroids, comorbidity and extra articular RA was associated with pre-mature mortality in our sample.
Widdifield et al, Trends in Excess Mortality among Patients with Rheumatoid Arthritis in Ontario, Canada. Arthritis Care & Research 2015 [in press].
Disclosure of Interest None declared