Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by chronic inflammation of joint tissues (1, 2). It can affect any synovial joint, with initial symptoms often manifesting as swelling, pain, and deformation in the small joints of hands and feet, potentially progressing to larger joints (3). RA impacts individuals of all ages, including males, females, and children, exhibiting significant regional variations in incidence and prevalence worldwide (4). Research indicates that the incidence of RA increases with age, peaking between 60 and 70 years. In the absence of adequate treatment, the disease can lead to progressive joint damage, deformity, chronic pain, long-term disability, and premature mortality (5). Additionally, RA imposes substantial socioeconomic burdens due to ongoing medical needs and a reduced quality of life (6).

Previous studies have reported the global burden of RA at regional or national levels using World Health Organization (WHO) databases or older Global Burden of Disease (GBD) versions (7–11). In addition to assessing the overall burden of RA, previous research has primarily focused on specific patient groups, such as women of reproductive age, children and adolescents, and the working-age population (6, 12–15). While these studies have provided valuable insights into the epidemiology and risk factors associated with RA, a comprehensive analysis specifically addressing the older adult population remains absent. In recent years, RA prevalence and associated health burdens have risen in many countries, aligning with population aging trends (16). Given the rapid global aging of the population and the unique clinical and socioeconomic challenges posed by RA in older adults, it is crucial to investigate its burden among individuals aged 60 years and older. To further investigate the correlation between RA and regional aging populations, we present the first study utilizing GBD 2021 to assess the global, regional, and national burdens of RA among individuals aged 60 years and older.

Our research leverages data from the GBD 2021 study, enabling cross-geographical, temporal, age, and gender comparisons. By integrating data from multiple sources, including life registration systems, censuses, health surveys, and epidemiological studies, and employing sophisticated statistical models, we aim to provide valuable insights into long-term trends of RA burden associated with population aging. This study aims to inform healthcare policies, resource allocation, and intervention strategies to effectively address the significant impact of RA, particularly within the context of a globally aging population.

Rheumatoid arthritis is a systemic autoimmune disease that affects multiple body systems, and if not treated promptly, it can cause severe damage to joints and their surrounding tissues. Therefore, research on the global burden of RA, particularly among the older adult population, is crucial. To our knowledge, this study is the first to comprehensively describe the incidence, prevalence, mortality, and DALYs rates of RA among individuals aged 60 and older across 204 countries. Our analysis includes global, regional, and national levels, covering data from 1990 to 2021. Compared with previous studies, this research utilizes GBD 2021 and improved methodologies, providing more accurate and comprehensive estimates of the RA burden. In particular, we have incorporated more data on individuals aged 60 and above, the primary age group for RA incidence and burden. Through cross-regional and temporal comparisons, we have uncovered the geographic diversity and locational differences in the RA burden, which can assist countries and regions in formulating more precise response strategies. Additionally, we have conducted stratified analyses of global trends by gender, age, and SDI, allowing us to focus on the disease burden across different groups for targeted interventions.

Our study reveals that in 2021, ASIR of RA for the entire population aged 60 and above was 30.32 per 100,000 people, and ASPR was 726.91 per 100,000 people. Compared with 1990, these two rates increased by 21.91 and 14.38%, respectively. Furthermore, our research highlights some significant trends in the RA burden from 1990 to 2021. Although the ASIR and ASPR of RA rose during certain periods, inflection points were also observed, particularly in recent years, where ASDR and the age-standardized DALYs rate of RA has shown a declining trend. This may be attributed to improved effectiveness of RA treatments, the promotion of early interventions, and enhanced public awareness of RA. Overall, the burden of RA remains significant globally, impacting not only the physical health and quality of life of patients but also imposing a socioeconomic burden.

An analysis of the incidence, prevalence, mortality, and DALYs rate of RA among older adult individuals across different genders and age groups has revealed that all these four indicators are higher for females compared to males, aligning with the findings of Safiri et al. (10) and Shi et al. (18). Age-stratified research indicates that in 2021, the incidence of RA among individuals aged 60 and above globally increased with age, peaking in the 65–69 age group, followed by a decline. Notably, RA mortality correlates positively with population aging. Furthermore, the prevalence and DALYs rates peak in the 75–79 and 85–89 age groups, respectively, highlighting the need for prevention and treatment strategies prior to these specific age periods. It is worth noting that this study reaffirms the substantial proportion of the global RA burden borne by females, potentially linked to sex hormone levels and their impact on the immune system. Existing research suggests that, as anti-inflammatory hormones, androgens inhibit humoral and cellular immune responses, whereas estrogens enhance humoral immune responses (19). A study on RA patients found significantly reduced concentrations of gonadal and adrenal androgens, particularly testosterone, dihydrotestosterone, and dehydroepiandrosterone sulfate, in bodily fluids (including blood, synovial fluid, smears, and saliva) (20). This finding implies that decreased levels of these immunosuppressive androgens may contribute to the adverse progression of RA. Therefore, females should pay closer attention to RA prevention and treatment, and considering therapeutic modulation to balance hormone levels could be a worthwhile direction to explore in advanced biological therapies for RA.

Upon deeper examination of the relationship between SDI and the age-standardized DALYs rate across different regions and countries, we observe a complex, non-linear association. We also find that the burden of RA is not confined to countries at specific development levels but is widespread across nations and regions with varying SDI levels. This finding corroborates with the earlier analysis by Safiri et al. (10) based on the GBD 2017, further attesting to RA as a global health concern. Additionally, variations in RA incidence and burden exist among different regions and countries, possibly attributed to environmental risk factors, discrepancies in healthcare policies, and accessibility to health services. Notably, the ASIR, ASPR, and age-standardized DALYs rate for RA among individuals aged 60 and above is highest in the Australasia region. In Australasia, which includes Australia and New Zealand, the percentage of individuals over the age of 60 significantly exceeds the global average (21). As the population ages, an increasing number of individuals develop RA, live with its effects, and experience related disabilities. Moreover, the region’s high prevalence of obesity (22)—recognized as an independent risk factor for RA—aggravates the condition. Adipose tissue in obese individuals secretes pro-inflammatory substances, such as leptin and interleukin-6, which promote immune responses, thereby intensifying autoimmune reactions and elevating the risk of RA-related complications (23). Both environmental factors and genetic predispositions play critical roles in the etiology of RA (24). Specific populations, including Indigenous Australians and New Zealand Māori, may possess susceptibility alleles, particularly in the HLA-DRB1 region (25), further predisposing them to RA. Although the high diagnostic rate in Australasia indicates a strong capacity for detection, the persistently high rates of disability suggest deficiencies in disease management, particularly concerning timely and effective interventions for high-risk groups. Conversely, while RA prevalence remains relatively low in Southeast Asia—especially in Cambodia, Myanmar, and Vietnam—the region paradoxically exhibits some of the highest annual incidence growth rates globally. This apparent contradiction likely stems from intersecting challenges: diagnostic limitations and barriers to therapeutic access within developing healthcare systems, compounded by a cultural normalization of geriatric arthralgia that delays clinical presentation. In conclusion, the complex interplay of demographic, metabolic, genetic, and healthcare access factors contributes to the regional disparities in the burden of RA. Tailored strategies—ranging from improved early diagnosis and optimized resource allocation to culturally sensitive interventions—are urgently needed to alleviate the overall health burden of RA.

A study published by the GBD 2021 Rheumatoid Arthritis Collaborators in Lancet Rheumatol predicts a continued increase in RA prevalence by 2050, underscoring the importance of prevention and treatment (5). When developing health promotion strategies, emphasis should be placed on RA risk factors such as smoking, hormones, stress, and obesity, with smoking being a well-established primary risk factor for RA that warrants precise monitoring (26, 27). A related study proposed several recommendations targeting known factors associated with RA risk to prevent its development (28). These suggestions include smoking cessation, reducing exposure to silica, dust, and occupational risks, maintaining a healthy weight, increasing leisure-time physical activity, maintaining good oral hygiene, maximizing breastfeeding where possible, striving for a high-quality diet while avoiding high-salt intake, consuming ample omega-3 fatty acids and fish, reducing consumption of sugar-sweetened soft drinks, moderate alcohol consumption, and maintaining adequate vitamin D levels. These recommendations provide valuable guidance for developing RA prevention strategies tailored to individuals aged 60 and above, especially considering the specific risks and challenges this age group may face. Future research can further explore the effectiveness of these preventive measures in reducing RA incidence and mitigating the disease burden, thereby providing a more scientific basis for public health policy formulation.

Existing literature predominantly emphasizes the significance of early diagnosis of RA, the timely initiation of treatment, and the early attainment of optimal remission targets (29, 30). Therefore, to more effectively reduce the global burden of RA, we urge governments, health agencies, and all sectors of society to increase support for early RA diagnosis and treatment. This includes, but is not limited to, enhancing public awareness of RA, strengthening screening capabilities at primary healthcare facilities, promoting effective treatment protocols, and optimizing the allocation of healthcare resources. Simultaneously, we must continually monitor advancements in RA treatment, such as the application effects of innovative therapies like biologics and small-molecule targeted drugs, to timely adjust and optimize treatment strategies. In recent years, with the development of new drugs, biologics have become an integral part of RA treatment, significantly improving disease activity and patient quality of life. Notably, JAK inhibitors tofacitinib and baricitinib are widely used in routine clinical practice (31). Although high-income regions have widely adopted biologic or targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), traditional medications like methotrexate and sulfasalazine remain effective and economical choices globally (5). It is worth mentioning that methotrexate tablets are listed in the WHO Model List of Essential Medicines (32). Although biologic or targeted synthetic DMARDs may show more pronounced efficacy (33), their high costs limit their application in low- and middle-income countries. Therefore, increasing the use of low-cost traditional DMARDs and raising awareness of early RA diagnosis and treatment are crucial for alleviating the global burden.

However, this study also has limitations. Firstly, it primarily relies on the GBD 2021 database, thus subject to variations in data quality and availability. Data from low- and middle-income countries may particularly suffer from issues of quality, comparability, accuracy, and completeness, affecting the comprehensiveness and accuracy of the findings. Secondly, variations exist in RA screening, assessment, and treatment across countries, with challenges faced particularly by less developed nations. This limits the representativeness of the statistical data and may lead to underestimation or overestimation of the RA burden in certain regions or countries. Lastly, the RA data included in GBD 2021 do not differentiate between disease stages nor contain sufficient risk factors. This constrains our in-depth analysis of the RA burden and prevents the identification of risk factors in individual regions and countries, thereby affecting the targeted nature of policy formulation.

This study finds that from 1990 to 2021, the global ASIR and ASPR of RA among individuals aged 60 and older showed an overall upward trend, while the ASDR and age-standardized DALYs rate declined. Despite the effectiveness of early diagnosis, preventive measures, and novel treatments in recent years, RA remains a global public health challenge. Future efforts should focus on enhancing early diagnosis, optimizing treatment, and raising public awareness. When formulating RA prevention and control policies, special attention should be given to the older adult population, especially older adult females, to mitigate the burden of RA.