FGF-21 Levels and Physical Functioning in Rheumatoid Arthritis

elderly man walking in park
High levels of circulating FGF-21 may help identify patients with RA at increased risk for worsening physical function.

High levels of circulating fibroblast growth factor-21 (FGF-21) may help identify patients with rheumatoid arthritis (RA) at increased risk for worsening physical function, according to study results published in the Journal of Rheumatology.

FGF-21 is an adipokine that is upregulated during metabolic stress. The objective of the current study was to determine the association between FGF-21 and adverse changes in physical function and body composition in patients with RA.

A total of 113 patients with RA (ages, 18-70 years) who were treated at the University of Pennsylvania and Philadelphia VA Medical Center Rheumatology practices were enrolled. All participants underwent whole body dual energy absorptiometry and peripheral quantitative computed tomography to quantify lean and fat mass and muscle density, at baseline and follow-up (median, 2.68 years; n=84). Muscle strength at the hand and knee was assessed using dynamometry, and the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB) were used to evaluate physical function. Levels of FGF-21 were measured as both a continuous and categorical variable.

Older age, active smoking, cardiac disease, longer RA duration, greater body mass index, and several measures of body fat, were all found to be associated with higher FGF-21 levels in univariate models. Higher estimated glomerular filtration rate and active treatment with methotrexate were associated with lower levels of FGF-21. No association between RA disease activity or severity and FGF-21 levels were detected in multivariate models, and only age, visceral fat area, methotrexate use, and current smoking were found to be moderately associated with FGF-21 levels.

Furthermore, an association between FGF-21 levels and a set of inflammatory cytokines (ie, tumor necrosis factor receptor type I, YKL-40, vascular endothelial growth factor, and resistin) was established

The highest quartile of FGF-21 levels was associated with worse HAQ (β coefficient [ie differences associated with1 standard deviation, SD greater baseline FGF-21 levels], 0.34; 95% CI, 0.039-0.63; P =.03) and SPPB (β, -1.68; 95% CI, -2.94 to -0.41; P =.01) scores, after adjusting for potential cofounders (eg, age, gender, current smoking, visceral fat area, and methotrexate use). The top FGF-21 quartile at baseline was also associated with a more rapid rate of decline in SPPB scores over time (β, -0.57; 95% CI, -1.04 to -0.091; P =.02) and a greater risk of clinically meaningful worsening of HAQ score (odds ratio, 2.37 per 1 SD; 95% CI, 1.21-4.64; P =.01).

Study limitations include the small sample size, potential uncontrolled confounders, and limited statistical power to determine associations between FGF-21 levels and cause-specific mortality.

“This study builds upon existing research by demonstrating temporal relationships between FGF-21 and long-term functional changes in [patients with] RA,” concluded the researchers.


Gould PW, Zemel BS, Taratuta EG, Baker JF. Circulating fibroblast growth factor-21 levels in rheumatoid arthritis: associations with disease characteristics, body composition, and physical functioning (published online, Nov 1, 2020). J Rheumatol. doi: 10.3899/jrheum.200673