Trends in Rheumatoid Arthritis Mortality in the United States, 1999-2020.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with systemic complications and increased mortality risk. Advances in RA treatment (early aggressive therapy, biologics) since the late 1990s have improved disease control and were expected to reduce mortality. We analyzed national trends in RA-related mortality from 1999 to 2020 to assess overall changes and disparities by sex, age, race/ethnicity, region, and urbanicity in the United States. Materials and Methods: We conducted a retrospective time-trend analysis using the cause of death WONDER multiple-cause-of-death database. Deaths among U.S. residents aged ≥25 years with RA as the underlying cause (ICD-10 codes M05.x, M06.x, M08.0) from 1999 to 2020 were extracted. Age-adjusted mortality rates (AAMR) per 100,000 (2000 US standard population) were calculated overall and stratified by sex, age group, race/ethnicity, census region, and metropolitan versus nonmetropolitan residence. Joinpoint regression was used to evaluate changes in trends and estimate annual percent change (APC). Results: A total of 210,156 RA-related deaths occurred from 1999 to 2020. The AAMR declined from 5.65/100,000 in 1999 to a nadir of 3.33 in 2019 - an average annual decrease of about -2% to -3%, but then rose to 4.07 in 2020. Female patients had higher RA mortality than males throughout (2020 AAMR 5.31 vs. 2.51). Both sexes experienced significant mortality declines through 2018 (female APC -2.4%; male APC -3.0% overall), followed by a sharp increase in 2018-2020 (female APC +9.1%; male +6.3%). By age, the 65+ years group accounted for the vast majority of RA deaths and saw the largest absolute decline (AAPC -2.1%), whereas younger age groups had lower rates and smaller or no improvements. RA mortality fell across all major racial/ethnic groups except American Indians/Alaska Natives. In 2018, non-Hispanic White AAMR dropped to ~3.2, Black ~2.8, Hispanic ~2.7, and Asian/Pacific Islander ~1.8, while Native American rates remained high (~8+). A significant rebound in 2020 was observed, especially among Black and Hispanic populations. Regionally, the Midwest and West had the highest RA mortality and the Northeast the lowest, but all regions showed parallel downward trends through 2018 (each APC ~-2.6% to -2.9%) with an upward inflection in 2020. RA mortality in non-metropolitan (rural) areas was consistently higher than in metropolitan areas (e.g., 2020 AAMR 5.3 vs. 3.8), despite similar relative declines pre-2018 and increases in 2020 (rural APC +9.9% vs. urban +8.8% for 2018-2020). Conclusion: From 1999 to 2019, U.S. RA mortality rates significantly decreased, likely reflecting improved RA treatments and cardiovascular risk management. These gains, however, were not shared equally; Native Americans and rural residents had persistently higher mortality and less improvement. Alarmingly, RA mortality rose in 2020, coinciding with the COVID-19 pandemic, which may have disproportionately affected RA patients. Ongoing efforts are needed to understand and address the recent increase and to close persistent demographic gaps in RA outcomes.