Background Fatigue (FTG) is a symptom commonly reported by patients with rheumatoid arthritis (RA). Little is known about its nature and etiology. The number of studies including fatigue as an outcome measure has increased rapidly during recent years and is considered a potential marker of RA disease activity in the clinic (1). In order to judge whether a given change in any disease marker in the individual patient is due to “measurement error” or to real change it is essential to know how large the natural variation of the disease marker is when the disease activity is constant.
Objectives The purpose of the present study was to examine intra-individual FTG fluctuations in patients with stable RA during treatment with a biological agent.
Methods 233 RA patients treated with a biological agent and with stable disease activity were identified in the Danish registry for biological treatment in rheumatology (DANBIO). Stable disease activity was defined as a change in DAS28-CRP ≤0.6 between two consecutive visits with complete clinical data sets available including FTG. Paired data from a single set of such two consecutive visits were extracted for each patient. Data comprised DAS28-CRP and its individual components, HAQ and global assessment of the patient (PaGl) and the physician (PhGl) as well as patient reported FTG scored on 0-100 visual analogue scales (VAS). Bland-Altman analyses were used to assess the lower and upper 95% limits of agreement between the two consecutive FTG assessments and the corresponding bias (the mean of individual differences). Associations between intra-individual inter-visit differences (Δ) in FTG and in other measures of disease activity were evaluated using Pearson's linear correlation analyses and by stepwise multiple regression with ΔFTG as the dependent variable. A p-value ≤0.05 was considered statistically significant.
Results Mean age was 60±15 years, female/male ratio 3.2, mean time from treatment start to the first visit 136.1±117.8 (range 0-485) weeks, mean inter-visit duration time 22.3±20.7 weeks, mean DAS28 3.1±1.2 and mean FTG 43.3±27.6. Mean ΔDAS28-CRP was 0.0±0.3 (range -0.6 to 0.6) (NS). The bias for FTG was 0.9±18.8 (NS) and the lower and upper limits of agreement -35.9 and 37.7, respectively. No significant correlation was found between the absolute value of ΔFTG and the inter-visit duration time (r =0.043, NS). ΔFTG was weakly correlated with ΔPain (r =0.33, p<0.01) and ΔPaGl (r =0.39, p<0.001) and were not significantly correlated with change in any other single measure of disease activity or ΔDAS28-CRP. In a multiple regression analysis including Δ of all disease activity measures including DAS28-CRP as independent variables, ΔFTG was significantly predicted by only ΔPaGl (beta =0.26, p<0.001) and ΔPain (beta =0.15, p<0.05). No statistically significant difference in FTG or ΔFTG was found between males and females.
Conclusions In individual RA patients, large fluctuations in FTG with no relation to time intervals were observed although the disease activity was unchanged. If FTG is considered to reflect disease activity, changes in FTG less than approximately 35 on a VAS-scale may be interpreted as natural variation or pure measurement error.
Thyberg I et al. Factors related to fatigue in women and men with early rheumatoid arthritis: the Swedish TIRA study. J Rehabil Med 2009; 41: 904-12.
Disclosure of Interest None declared