Background/Purpose: In geriatrics, fatigue has been shown to be a harbinger of future functional decline. Fatigue is associated with poor function in systemic lupus erythematosus (SLE), but previous studies have not examined the longitudinal relationship between fatigue and poor function. In this analysis, we examine whether fatigue is a risk factor for subsequent functional decline among individuals with SLE.

Methods: Analyses use data from the Lupus Outcomes Study (2003-2011) obtained through annual structured telephone interviews. All participants have physician-confirmed SLE. Fatigue was measured with the SF-36 Vitality subscale. Scores range from 0–100, and higher scores reflect greater fatigue. Function was measured with the Valued Life Activities (VLA) disability scale, which has been validated in SLE. The VLA presents 28 life activities ranging from self-care to social, recreational, and work activities; respondents rate the difficulty they have in performing each on a 0 (no difficulty) to 3 (unable to perform) scale. Two VLA scores were calculated: mean difficulty and the percent of VLAs an individual was unable to perform. Analyses aimed to determine if fatigue at one time point (T1) was a risk factor for a decline in functioning between T1 and the subsequent year (T2). Declines were defined to approximate a clinically important difference: an increase of 0.5 SD in mean difficulty (0.3 points) or an increase ≥10% in the percent of VLAs unable to perform. Analyses include up to 8 pairs of years of interviews, using generalized estimating equations to account for multiple observations of individuals. Multivariate analyses controlled for age, sex, disease duration, disease activity (Systemic Lupus Activity Questionnaire, SLAQ), depressive symptoms (Center Epidemiologic Studies Depression scale, CESD), and presence of end-stage renal disease. A secondary analysis included only individuals under age 65.

Results: The primary analysis included 5105 observations of 1019 individuals, 92% female, with mean age 47±13 years, and mean disease duration 13±9 years.  At initial interviews, mean fatigue score was 54.1±23.7. In 11.8% of paired observations, there was a functional decline by mean difficulty, and in 7.8%, a decline by percent of activities unable to perform. In bivariate analysis, T1 fatigue was a significant risk factor for subsequent functional decline between T1 and T2 (see table).  After adjustment, T1 fatigue remained a significant risk factor for functional decline.  Results of analyses including only age‹65 were similar.

Conclusion:   Fatigue appears to be a risk factor for subsequent functional decline among individuals with SLE, even after accounting for other factors.  Moreover, the risk is not confined to those age ≥65.  High levels of fatigue may be a signal for impending functional decline, so can serve as an indicator for proactive intervention to prevent or minimize such declines. 

Odds of functional decline associated with 10-point worsening of fatigue score
	OR (95% CI)
	Bivariate	Multivariate*
Total sample (5105 observations, 1019 individuals)
Mean VLA difficulty (increase ≥0.5 SD, or 0.3 points)	1.11 (1.07, 1.15)	1.06 (1.01, 1.11)
% VLAs unable to perform (increase ≥10%)	1.28 (1. 22, 1.35)	1.13 (1.06, 1.20)
Under 65 years only (4496 observations, 926 individuals)
Mean VLA difficulty (increase ≥0.5 SD, or 0.3 points)	1.12 (1.07, 1.16)	1.05 (1.00, 1.11)
% VLAs unable to perform (increase ≥10%)	1.30 (1. 23, 1.37)	1.13 (1.05, 1.22)
* adjusting for age, sex, disease duration, SLAQ, depressive symptoms, and ESRD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fatigue-is-a-risk-factor-for-subsequent-functional-decline-in-sle/