Lower treatment efficacy in elderly-onset RA and elderly RA patients, compared with younger patients, has been reported by many studies that have examined therapeutic agents and outcomes. It has been reported that elderly patients have higher risks of adverse reactions, including infections, and lower rates of drug retention [8, 18]. Moreover, most reports define “elderly” as the age range from 60–75 years old. There is little data on the patient population older than 80 years, which is expected to increase in our aging society. Recent advances in drugs and therapeutic strategies have improved the outcomes of RA [1, 2]. However, to date, there is no satisfactory answer to the question of whether, in elderly patients, these advances have outweighed the effects of aging on disease activity control and functional prognosis. Japan is the most aged country in the world [19], and the present cohort study followed treatment options and outcomes for 10 years in a population that included patients older than 80 years. It is expected to provide some answers to the clinical questions raised above.

When considering the change in the numbers of RA patients from 2011 to 2020, two factors need to be considered. First, the Department of Rheumatology was established in our hospital in 2004; the increase in patients since 2010 may have been due to the expansion of the department. Thus, the increased number of patients during this period does not necessarily imply that the number of RA patients in the region increased. Second, our hospital is located in an area with a particularly large elderly population, even by Japanese standards. In Higashiyama Ward, the proportion of residents aged ≥ 65 was estimated to be 32.9% in 2020, compared with 28.6% in Japan as a whole [20]. This implies that the effects of aging shown by this study may be more pronounced in Japan as a whole, where the population is aging rapidly. The average age of the RA patients included in this study increased by 3.8 years over the 10-year period. The annual number of patients aged in their 70s increased from 27.3% to 36.1%; the annual number of patients aged 80 years and older increased from 8.1 to 17.2%, which indicates that the RA patient population is aging rapidly.

In general, it is known that the proportion of males increases in elderly-onset RA patients [8, 18]; in this study, there was no change in the sex ratio. This may be because the increase number of male RA patients was offset by an increase in deaths; the estimated 2020 average life expectancy of males in Japan is 81.64 years, 6.1 years shorter than that of females (87.74 years) [20].

When we examine changes in the choice of therapeutic agents and outcomes over the past 10 years, we believe intensive drug therapy was used whenever possible, taking into account the patient’s age and physical and social situation. MTX is said to be an anchor drug for RA. In this study, MTX was the mainstay of RA treatment, used in more than 60% of patients, although at a lower dosage than in Europe and the United States. The frequency of MTX use decreased after the age of 70, especially in patients aged ≥ 80 years (40.8%). The amount of MTX used also decreased. PRED was used more frequently in elderly patients, but the dosage (4.41–4.91 mg/day) did not differ depending on the age. MTX has serious side effects, as previously reported, which are especially to be avoided in elderly patients. It is presumed that low-dose steroids were selected as alternative treatments [8, 21, 22]. The usage of biologics, as a whole, tended to decrease with aging; especially IL6 receptor inhibitors were avoided in patients older than 80s. On the contrary, the use of abatacept increased in very old patients. This may be due to evidence in favor of abatacept, compared with IL6 receptor inhibitors and TNF inhibitors, regarding the risk of severe infection [23].

Disease activity in RA improved almost linearly in all age groups over the 10-year period. Considering that there was no change in all ages with respect to MTX dosage during the 10 years, it is assumed that there was no significant change in the severity of the patients. Therefore, we believe that this is mainly due to the emergence of new therapeutic agents and the penetration of intensive therapeutic strategies. Treatment outcomes by age group showed that disease activity deteriorated almost linearly from the < 60 years group to the ≥ 80 years group. This is probably related to the fact that the frequency of use of highly effective drugs, such as MTX and biologics, decreases with age. However, improvement in disease activity over the past decade was generally similar between patients aged > 80 years and those younger than 60 years, which indicates that advances in intensive drug therapy have improved outcomes in elderly patients and younger patients equally.

Physical function, as assessed by the JHAQ, and QOL, as indicated by EQ5D, also improved in all age groups over the decade. This indicates that tight control of disease activity in RA is useful for improving physical function and QOL in both young and elderly patients. However, the pattern of change by age group for both differed slightly from that of disease activity. The magnitude of change in deterioration increased with age. Several causal factors must be considered. In terms of physical function, it is important to consider the deterioration caused by residual joint destruction, and the irreversible component of a health questionnaire [11, 24]. Joint deformities and contractures caused by RA will persist, even after achieving remission with treatments. Second, age-related changes that are not related to RA, such as osteoarthritis, osteoporosis, and sarcopenia, increase in prevalence with age and contribute to functional impairment [11, 25]. Psychological depression is believed to be a third factor contributing to deterioration of QOL. It is well known that RA patients are prone to depression [26], which is exacerbated by aging and associated physical disabilities [27]. The psychological burden of RA may be increased by age-related changes in the home and social environment. These three problems, which worsen HAQ and QOL in late-stage elderly RA patients, are expected to have an increasing impact. Non-pharmacological approaches, such as physical care and psychological support, should be provided along with pharmacotherapy for these patients [28, 29].

The study has several limitations. The living environment of elderly patients and their treatment choices for RA are influenced by economic, cultural, and political factors; therefore, regional differences are likely to be significant. This study was conducted at a single hospital in Japan for a limited period of time; it may not necessarily apply to different social situations or time periods. Second, this study did not examine several variables that may have a significant impact on physical function and QOL, such as comorbidities and socioeconomic status. How these variables relate to the age and disease activity presented here is a very important question that will have to be examined in the future. Third, the number of physicians who treated the patients was limited; their treatment strategies and drug choices may not have always been standardized. However, it can be inferred from the aforementioned medication details that the RA patients registered in this study were treated intensively to achieve the treatment target.

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