Roles of Postdiagnosis Accumulation of Morbidities and Lifestyle Changes in Excess Total and Cause-Specific Mortality Risk in Rheumatoid Arthritis

Objective To elucidate how postdiagnosis multimorbidity and lifestyle changes contribute to the excess mortality of rheumatoid arthritis (RA). Methods We performed a matched cohort study among women in the Nurses' Health Study (1976-2018). We identified women with incident RA and matched each by age and year to 10 non-RA comparators at the RA diagnosis index date. Specific causes of death were ascertained via death certificates and medical record review. Lifestyle and morbidity factors were reported biennially; 61 chronic conditions were combined into the Multimorbidity Weighted Index (MWI). After adjusting for baseline confounders, we used inverse probability weighting analysis to examine the mediating influence of postindex MWI scores and lifestyle factors on total, cardiovascular, and respiratory mortality, comparing women with RA to their matched comparators. Results We identified 1,007 patients with incident RA and matched them to 10,070 non-RA comparators. After adjusting for preindex confounders, we found that hazard ratios (HRs) and 95% confidence intervals (95% CIs) were higher for total mortality (HR 1.46 [95% CI 1.32, 1.62]), as well as cardiovascular (HR 1.54 [95% CI 1.22, 1.94]) and respiratory (HR 2.75 [95% CI 2.05, 3.71]) mortality in patients with RA compared to non-RA comparators. Adjusting for postindex lifestyle factors (physical activity, body mass index, diet, smoking) attenuated but did not substantially account for this excess RA mortality. After additional adjustment for postindex MWI scores, patients with RA had HRs of 1.18 (95% CI 1.05, 1.32) for total, 1.19 (95% CI 0.94, 1.51) for cardiovascular, and 1.93 (95% CI 1.42, 2.62) for respiratory mortality. Conclusion We found that MWI scores substantially accounted for the excess total and cardiovascular mortality among women with RA. This finding underscores the importance of monitoring for the total disease burden as a whole in monitoring patients with RA.