ORIGINAL ARTICLE Causes of Death in Rheumatoid Arthritis: How Do They Compare to the General Population? JESSICA WIDDIFIELD , 1 J. MICHAEL PATERSON , 2 ANJIE HUANG , 3 AND SASHA BERNATSKY 4 Objective. To compare mortality rates, underlying causes of death, excess mortality, and years of potential life lost (YPLL) among patients with rheumatoid arthritis (RA) relative to the general population. Methods. We studied an inception cohort of 87,114 Ontario-based RA patients and 348,456 age/sex/area-matched gen- eral population comparators from years 2000 to 2013. All-cause, cause-specific, and excess mortality rates, mortality rate ratios (MRRs), and the YPLL were estimated. Results. A total of 11,778 RA patients (14%) and 32,472 comparators (9%) died during 508,385 and 1,769,365 patient-years of follow-up, respectively, for corresponding mortality rates of 232 (95% confidence interval [95% CI] 228–236) and 184 (95% CI 182–186) per 10,000 patient-years. The leading causes of death in both groups were diseases of the circulatory sys- tem, cancer, and respiratory conditions. Increased mortality for all-cause and specific causes was observed in RA patients relative to the general population. MRRs were elevated for most causes of death. Age-specific mortality ratios illustrated a high excess mortality among RA patients <45 years of age for respiratory disease and circulatory disease. The YPLL for RA patients was 7,436 per 10,000 persons, compared with 4,083 YPLL among those without RA. Conclusion. Among most causes of death, mortality rates were increased in RA patients relative to the general popula- tion. The potential life years lost (before the age of 75 years) among RA patients was roughly double that among those without RA, reflecting higher rate ratios for most causes of death and RA patients dying at earlier ages. INTRODUCTION Numerous studies have established that patients with rheumatoid arthritis (RA) die earlier than their general population counterparts (1–4), but few studies have eval- uated causes of death in RA patients relative to the gen- eral population (5–9). Previous research has shown that causes of death in RA patients often mirror those in the general population, with cardiovascular disease, cancer, and respiratory disease being among the leading causes (7,10,11); however, the relative excess mortality for causes of death by patient age is often not reported due to insufficient sample sizes. Further, studies from inception cohorts have shown con- flicting results (12–15). Some inception cohorts that have failed to show increased mortality were limited in both fol- low-up and generalizability. Many inception cohorts are drawn from rheumatology referral centers and are therefore less broadly representative of real-world patients who have more variable access to rheumatology care. It is also diffi- cult to determine (from studies with insufficient follow-up or that lack general population comparators) the years of The views expressed herein are those of the authors and not those of the funding sources. No endorsement by the Institute for Clinical Evaluative Sciences or the Ontario Ministry of Health and Long-Term Care is intended or should be inferred. Supported by the Catherine and Fredrik Eaton Charitable Foundation, the Canadian Network for Advanced Interdis- ciplinary Methods (CAN-AIM) for comparative effectiveness research funded by the Canadian Institutes of Health Research (CIHR) Drug Safety & Effectiveness Network (DSEN), and supported by the Institute for Clinical Evalua- tive Sciences (ICES), a nonprofit research corporation funded by the Ontario Ministry of Health and Long-Term Care (MOHLTC). Parts of this material are based on data and/or information compiled and provided by Canadian Institutes of Health Information (CIHI). Dr. Widdifield is recipient of a Fellowship Award from The Arthritis Society and the Canadian Institutes of Health Research (CIHR) Banting. Dr. Bernatsky is recipient of a career award from the Fonds de la recherche en Sant e du Qu ebec. 1 Jessica Widdifield, PhD: Sunnybrook Research Institute, Toronto, Ontario, Canada, McGill University, Montreal, Quebec, Research Institute of the McGill University Health Centre, Montreal, Quebec, Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada, and University of Toronto, Toronto, Ontario, Canada; 2 J. Michael Paterson, MSc: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada, University of Toronto, Toronto, Ontario, Canada, and McMaster University, Hamilton, Ontario, Canada; 3 Anjie Huang, MSc: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; 4 Sasha Bernatsky, MD, FRCPC, PhD: McGill University, Montreal, Quebec and Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. Address correspondence to Jessica Widdifield, PhD, Sunnybrook Research Institute, MG 352 - 2075 Bayview Avenue, Toronto ON, M4N 3M5. E-mail: jessica.widdifield@ utoronto.ca. Submitted for publication October 11, 2017; accepted in revised form February 13, 2018. 1748 Arthritis Care & Research Vol. 70, No. 12, December 2018, pp 1748–1755 DOI 10.1002/acr.23548 © 2018, American College of Rheumatology