Weight Change During the Early Rheumatoid Arthritis Period and Risk of Subsequent Mortality in Women With Rheumatoid Arthritis and Matched Comparators

Abstract

Objective: To investigate whether weight change during the early rheumatoid arthritis (RA) period is associated with subsequent mortality and to evaluate whether there is an RA-specific effect.

Methods: We identified patients with incident RA during the Nurses' Health Study (NHS; 1976-2016) and created a comparison cohort by matching each RA patient with up to 10 non-RA comparators by age and calendar year of the RA diagnosis (index date). To capture weight change around the early RA period ("peri-RA/index"), we used weight measurements collected 2-4 years before and 2-4 years after the index date. We used Cox regression analysis to estimate hazard ratios (HRs) for mortality according to peri-RA/index weight change categories, separately in each cohort and in the combined cohorts, evaluating for an RA-specific effect.

Results: Among 121,701 women in the NHS, 902 patients with incident RA were identified and matched to 7,884 non-RA comparators. In the RA cohort, 371 deaths (41.1%) occurred during a mean follow-up of 17.0 years after the early RA period, and 2,303 deaths (29.2%) occurred in the comparison cohort during a mean follow-up of 18.4 years. Weight loss of >30 pounds during the peri-RA period had a hazard ratio (HR) for mortality of 2.78 (95% confidence interval [95% CI] 1.58-4.89) compared to stable weight; results in the comparison cohort were similar (HR 2.16, 95% CI 1.61-2.88). A weight gain of >30 pounds had no association with mortality in patients with RA (HR 1.45, 95% CI 0.69-3.07) or comparators (HR 1.19, 95% CI 0.89-1.59). For mortality, there was no statistically significant interaction between RA/comparator status and weight change category (P = 0.68).

Conclusion: Severe weight loss during the early RA period was associated with an increased subsequent mortality risk for women with and those without RA. These results extend prior observations by including non-RA comparators and finding no protective association between weight gain and mortality, providing evidence against an RA-specific obesity paradox for mortality.

Figure 1

Study design schematic for weight change in the early rheumatoid arthritis period among RA cases and matched comparators. Wedges indicate questionnaire cycles during 40 years of prospective follow-up in the Nurses’ Health Study.

Figure 2

Kaplan-Meier survival curves for mortality after the early RA or index period according to peri-RA or peri-index weight change among A) the RA cohort (n=902) and B) the comparison cohort (n=7,884).

Figure 3

Multivariable hazard ratios for mortality according to peri-RA or peri-index weight change, combining the RA and comparison cohorts into a single analysis (n=8,786).