Frailty Lowers Likelihood of Achieving Comprehensive Disease Control in RA, Study Finds

A study found that frailty reduced the likelihood of comprehensive disease control achievement by patients with rheumatoid arthritis (RA) being treated with a biologic agent.

Using the Comprehensive Rheumatologic Assessment of Frailty (CRAF), a study published in Clinical Rheumatology showed that frailty reduced the likelihood of comprehensive disease control (CDC) achievement by patients with rheumatoid arthritis (RA).

Frailty—a term defining a category of elderly adults who appear to be vulnerable and weaker compared with others with similar age and other characteristics—has been recently discussed in the context of inflammatory joint disease.

“Well-known in the geriatric field, where it has been documented that it is associated with multiple unfavourable outcomes (risk of hospitalization, institutionalization and death), frailty must also be recognized in other settings such as rheumatology since it is an evolutive but potentially reversible syndromic scenario,” the study authors said.

To determine its relation to CDC achievement in patients with RA being treated with a biologic agent, researchers followed 214 patients with RA for 12 months after introducing biological disease-modifying antirheumatic drugs (bDMARDs) to their therapy. After these 12 months, patients were either classified as achieving or not achieving CDC. Achievement was defined by the contemporary achievement of clinical remission, normal physical function, and absence of radiographic progression.

The patient population (N = 214) was mostly female (n = 162), with 145 reporting at least 1 medical comorbidity. The mean (SD) age was 60.2 (12.72) years, and the mean disease duration was 7.34 (2.79) years. More than half (57%) of participants received 5 to 8 drugs per day.

Patients were classified by frailty according to the CRAF. Of 214 participants, 84 (39.3%) were not frail, 57 (26.6%) were mildly frail, 14 (6.5%) were moderately frail, and 59 (27.6%) were severely frail. Researchers also performed a multivariable logistic regression to identify factors that could potentially predict CDC achievement.

Of the 214 participants, only 31 (14.4%) achieved CDC. Participants who achieved CDC experienced significantly lower changes or worsening in physical function and disease activity. There were no statistically significant changes in radiologic damage between the 2 groups.

Further, the prevalence of frailty was 27.6%, which is significantly higher in this cohort compared with other studies with a mean age around 70 years. According to the authors, frailty reduced the likelihood of CDC achievement in patients with RA treated with bDMARDs.

“The interrelationships between inflammation, physical fatigue, muscle dysfunction, pain and psychological factors have been suggested as implied pathogenic mechanisms of frailty in RA patients,” the authors said. “However, the specific mechanisms of frailty in RA have not been studied in detail.”

They also emphasized the importance of pain treatment, as pain can be a major predictor of frailty and contributor to vulnerability, dependency, and mortality. Additionally, depression and its relation to pain is another frailty-related factor, and a better understanding of how they interact can help identify other factors and preventive interventions.

Limited time intervals, reliance on patient-reported information, and the lack of investigation of certain medication effects were among the mentioned limitations of the study.

“The main strength of this study is the prospective observational design, and the novelty of using a dedicated frailty index should be emphasized,” the authors concluded. “The results of this study suggest dedicating more and more attention to frailty in patients with RA, in all its determinant variables, through dedicated tools such as CRAF or other validated frailty questionnaires.”


Salaffi F, De Angelis R, Farah S, Carotti M, Di Carlo M. Frailty as a novel predictor of achieving comprehensive disease control (CDC) in rheumatoid arthritis. Clin Rheumatol. 2021;40(12):4869-4877.. doi:10.1007/s10067-021-05744-1