Background/Purpose: Fatigue has been identified as a major concern for individuals with rheumatoid arthritis (RA) and has been endorsed as a core outcome measure. However, in order to develop adequate treatments for fatigue, its sources need to be identified.

Methods:   During home visits (n=160), assessments were made of fatigue (Fatigue Severity Index; FSI), self-reported sleep quality (Pittsburg Sleep Quality Index; PSQI), depression (Patient Health Questionnaire-9; PHQ9), usual levels of physical activity (International Physical Activity Questionnaire; IPAQ), RA disease activity (RA Disease Activity Index; RADAI), muscle strength (by hand-held dynamometer), functional limitations (Short Physical Performance Battery; SPPB), body composition (body mass index and percent fat mass by bioelectrical impedance), and pulmonary function (by spirometry). Blood was drawn to measure inflammatory markers (C-reactive protein [CRP], tumor necrosis factor-a [TNF], and interleukin-6 [IL-6]), RA-specific markers, anemia, and thyroid function, and information was collected on demographics, medication use, and smoking. The FSI average fatigue level over the past 7 days, rated on a 0-10 (no-severe fatigue) scale, was used as the outcome measure.  Analyses were first conducted to evaluate bivariate relationships with fatigue. Multivariate analyses, including all variables significantly associated with fatigue in the bivariate analyses, were then conducted to identify independent predictors of fatigue.

Results: Mean age (±SD) was 59 (±11), mean disease duration was 21 (±13) years, and 85% were female. Mean FSI rating was 3.8 (±2.0; range 0-10).  Significant bivariate relationships with fatigue are shown in the Table. No significant associations were found for age, sex, ethnicity, disease duration, knee extension or grip strength, TNF, IL-6, pulmonary function, or prednisone or biologic use (not shown). In multivariate analyses, obesity, RADAI, depression, and smoking remained significantly and independently associated with fatigue.

Table:  Factors associated with fatigue
	Bivariate	Multivariate*
	b (p)	b (p)
BMI obesity	1.56 (<.0001)	1.54 (.006)
Disease activity (RADAI)	0.68 (<.0001)	0.30 (.005)
Depressive symptoms (PHQ)	0.25 (<.0001)	0.12 (.002)
Sleep quality (PSQI)	1.21 (<.0001)	0.36 (.07)
Hip flexor strength	-0.03 (.004)	-0.006 (.52)
CRP	0.22 (.008)	-0.009 (.89)
Physical activity ≥150 minutes/week in moderate/vigorous activity	-1.20 (.0005)	-0.23 (.41)
Ever smoke	1.16 (.0008)	0.69 (.009)
* Multivariate model included all variables significantly associated with fatigue in bivariate analyses

 In additional analyses, performing ≥150 minutes/week of moderate/vigorous physical activity was associated with lower odds of obesity (OR=0.29 [95% CI 0.15, 0.55]), lower depression score (p=.002), and better sleep quality (p=.04), suggesting that that physical activity may have an indirect association with fatigue, mediated by these factors.

 Conclusion: In this cross-sectional study, much of RA fatigue appeared to arise from factors that are secondary to the disease process itself (obesity, poor sleep quality, and depression), but are commonly present in RA. In addition, physical inactivity appeared to play a role, although its effects were indirect.  Further research is warranted to determine the time-ordering of the relationships and if interventions that target modifiable lifestyle factors such as physical activity improve fatigue.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fatigue-in-rheumatoid-arthritis-is-associated-with-modifiable-lifestyle-factors/