Background/Purpose: Frailty predicts mortality in RA. In the general population, males have a higher risk of death than females despite lower levels of frailty.1 We evaluated how sex modifies the relationship between frailty and mortality in RA.

Methods: Participants from the Veterans Affairs Rheumatoid Arthritis (VARA) Registry enrolled between 1/2003 to 12/2020 were included. Follow up ended in 12/2022, allowing for at least 2 years of observation for each participant. Frailty was measured annually throughout the observation period using the VA Frailty Index (VA-FI), a validated deficit accumulation score based on >6000 diagnostic codes.2 Participants were categorized as robust or frail at enrollment using the established VA-FI cutoff of >0.2. Our primary model used multivariable Cox regression to evaluate the relationship between baseline frailty and mortality, with sex as an interaction term. A subsequent multivariable Cox model, including only those who have new onset frailty, evaluated sex differences in the risk of death starting at the time of frailty onset. Models were adjusted for baseline age (categorized by decade), race, BMI (normal/low vs. high), RF positivity, RA disease duration, DAS28-ESR, rheumatic disease comorbidity index (RDCI), prednisone use, conventional synthetic DMARDs and biologic DMARDs.

Results: 2,601 males and 344 females were included in the primary analysis, with average age 66 (10) for males and 55 (12) for females. Disease duration was 11.6 (11.5) years for males and 9.8 (9.8) years for females. An equal proportion of males and females were frail at baseline (28% and 27%, respectively). During follow-up, 1,301 (50%) males and 66 (19%) females died. Compared to robust males, robust females were less likely to die (aHR 0.45, [0.32-0.63]). Frailty was associated with an increased risk of death in frail males compared to robust males (aHR 1.37, [1.20-1.57]). The risk of death did increase in frail females, however, it was not significantly higher than that of robust males (aHR 1.01, [0.70-1.45]). The risk of death conferred by frailty was higher in females than males as represented by the significant interaction term between sex and frailty of 1.64 (p=0.051). The incident frailty analysis included 948 males with mean age 67.6 (0.39) and 95 females with mean age 64.9 (2.43) with 526 (55%) males and 26 (27%) females dying during follow-up. Females with incident frailty were less likely to die than males with incident frailty (aHR 0.59, [0.39-0.91]). Median survival time was shorter in newly frail males than females (6.50 vs >16.40 years, respectively); exact median could not be calculated for females due to less than 50% death among females.

Conclusion: Frailty in RA is associated with mortality and this relationship differs by sex. Males, regardless of frailty status, have a higher risk of death than females, yet frailty confers a higher relative risk of death in females. Males with incident frailty have a higher risk of death and shorter median survival times than females with incident frailty with RA, highlighting the need for early recognition and intervention in this group.References:(1) Gordon et al. Exp Gerontol 2017 (2) Orkaby et al. TJ Gerontol A Biol Sci Med Sci 2019

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/does-biological-sex-affect-mortality-in-frail-patients-with-rheumatoid-arthritis/