Patients with RA have an increasingly greater life expectancy because of the introduction of new drugs that improve control of the disease. However, this also means that more patients may be subject to frailty as they age. Caring for such patients therefore raises frailty as an additional challenge (19).
In this study, we attempted to clarify the characteristics associated with the frailty status and the frailty score, as well as the relationship between diagnosis or the frailty status and various clinical parameters such as aging, ADL, quality of life, state of disease activity, comorbidities, and dementia. We were afraid that disease activity would confound the frailty status; therefore, patients who had been treated for >1 year were picked up. Average disease activity calculated with SDAI in all generations were <ten, which means low disease activity level. As is generally accepted, aging has a close correlation with the Frailty status. In a comparison among generations, the prevalence of frailty increased with age in addition to the average frailty score. However, a remarkable finding in this study is that nearly one-fourth of RA patients in their sixties were included in the Frailty group. The prevalence was not significantly higher in the seventies age group, but the proportion of Pre-frailty status patients increased. Compared with Yamada’s report, every item for the diagnosis of frailty in patients aged >60 years in the present study demonstrated obviously higher values of positive ratio (Table 4) (12). These results suggest that physical instability in RA patients begins at a younger age than other populations reported previously (19, 20). This can result from long-lasting inflammation, leading to joint deformity, and fatigue or psychological burden (21). Even though RA treatment has been improved and disease activity is well controlled, these problems remain unsolved. The results in this study suggest that physical and psychological care is necessary for RA patients aged 60 and above to prevent frailty.
To provide further evidence, we evaluated the patient numbers in the EORA, oYORA, and yYORA frailty status groups. The results showed that EORA was significantly more common than YORA in the Frailty group, whereas EORA and oYORA were significantly more common in the Pre-frailty group than in the control group, indicating that elderly RA patients have a strong risk of frailty.
Gait status in particular seems to be the most important factor, because the most frequent factor in the five categories of frailty for the sixties age group was GS. This finding indicates that GS and gait instability are to be evaluated in patients in their sixties. GS loss was also the most popular symptom in the Frailty group. Gait ability evaluation is therefore essential for good control of physical stability in RA patients. A decline in ADL, particularly locomotive function, is closely related to aging. We found that GS was the most frequently reported symptom of frailty, suggesting that daily exercise is important to avoid frailty, as has been recommended by other investigators (22, 23). RA patients have a weak grip force or upper extremity weakness due to joint damage (24); however, upper extremity weakness does not always figure into frailty assessment. We recommend that more attention should be paid to locomotive functions for RA patients.
The EQ5D Activity category, a reflection of ADL functioning, significantly correlated with both the diagnosis of frailty and the frailty score. These results suggested that quality of life is strongly associated with frailty. Therefore, we conclude that further investigation addressing ADL to prevent frailty is necessary, which may lead the maintenance of quality of life.
It was also clear from this study that dementia is strongly correlated with the frailty status as well as aging. Frailty, aging, and dementia are likely to go hand-in-hand.
In comparison with the clinical background of RA for the frailty status, the sex, age at onset and at interview, ACPA, RF, SHS, HAQ-DI, CDAI, CRP, PS-VAS, N.com, dementia treated, GCS administration, MTX administration, and all parameters except b-/ts-DMARDs administration were investigated and demonstrated that significant factors that correlated with the frailty status significantly were ACPA, SHS, CRP, PS-VAS, N.Com, and GCS administration after aging was corrected, whereas age at interview, HAQ-DI, dementia treated, and GCS administration demonstrated significant correlation with the frailty score. These results suggested that such is the deepness of aging reflection in the frailty status. At the same time, frailty status is influenced by various factors, such as ACPA titer, joint deformation, ADL represented by the HAQ score, inflammation status represented with CRP, number of comorbidities, and GCS administration. These may be independent risk factors of the frailty status besides aging. Patients with the above risk factors tend to develop frailty; therefore, more careful attention is warranted. In these factors, the HAQ score, whether dementia treated or GCS administered, are the noticeable parameters for early detection of frailty.
One notably important factor is GCS administration, which declined the frailty score as shown in Table 2. Although short GCS administration is recommended in the EULAR recommendation for RA in 2016 (25), GCS administration should be considered with discretion.
Increased CRP levels were significantly correlated with the frailty status. Inflammation as reflected in serum markers has been identified as indicating increased risk of frailty in patients with RA (26). Our results are consistent with this finding, emphasizing the importance of controlling inflammation in patients with RA. Monitoring CRP levels is necessary not only to manage disease activity but also for addressing frailty.
The number of organ systems involved with comorbidities was significantly correlated with the frailty status. Prevalence of comorbidities showed obviously higher ratio than that obtained in Yamada’s report (12). However, no significant difference in frequency was demonstrated among generations except with dementia (Supplemental Table). These results were rather surprising as we expected the musculoskeletal and cardiovascular systems to be most strongly associated with frailty since disorders in those two systems can affect physical function. However, there was no correlation between musculoskeletal system disorders and frailty in this study. These findings may be because of the nature of the Frailty questionnaire. Three of the 5-item frailty score questions are subjective. Patients might indicate that they were not bothered by slower GS, short-term memory loss, or general fatigue and therefore would not be considered frail, despite objective evidence of a number of comorbidities. This may have confounded analysis of the association between comorbidities and frailty in accordance with the frailty score.
There are several major limitations to be considered when interpreting our results. (1) The cross-sectional study design did not allow for longitudinal observations. (2) The presence of dementia was determined on the basis of whether a patient was being treated for it, not on the basis of a diagnosis or stage of dementia. (3) The effects of other potential confounding factors — such as sex, muscle power, osteoporosis, polypharmacy, ethnicity, RA disease duration, and joint destruction — were not assessed.
There is no article that has investigated regarding frailty management for RA patients in our investigation scope; however, some cohort studies have described regarding frailty management. Of these, Leng et al. have reported that higher serum interleukin 6 (IL-6) levels and lower hemoglobin levels were observed in the frailty subjects. They concluded that potential increase in chronic inflammation state is related to the frailty status (26, 27). These results coincide with the results of our study that CRP level correlates with the frailty status. The Asia-Pacific Clinical Practice Guidelines for the Management of Frailty strongly recommends physical activity with a resistance training component along with various other physical activities, including balance training (28). These trainings control serum IL-6, one of the myokines (29) and would be a hint to manage frailty.
We investigated whether patients with RA had a frailty risk and the factors potentially associated with the frailty score. Although many factors, such as aging, being treated for dementia, GCS administration, ADL decline, especially particularly gait function or speed, and number of comorbidities, are confounded, RA patients may have a risk of falling into frailty in a younger age than those who are not suffering from RA. Elderly RA patients ≥ 60 have a strong risk of frailty or pre-frailty; therefore, controlling the physical functions of these patients is essential to avoid frailty.