Background The lack of association between fatigue and objective disease activity markers in patients with rheumatoid arthritis (RA) is counterintuitive since patients and doctors consider fatigue an indicator of underlying disease activity. We hypothesized that there is hardly any association between rather stable between-subject differences in levels of fatigue and disease activity, but that within-subject changes in fatigue are associated with fluctuations in disease activity. To examine this hypothesis we used a method –latent growth curve model analyses– that is able to disentangle between-subject differences and within-subject changes.
Objectives To examine if, in contrast to between-subject differences, within-subject changes in fatigue are associated with changes in objective markers of disease activity, i.e. erythrocyte sedimentation rate and swollen joint count.
Methods Consecutive patients with RA (n=248, mean age 53 years, 76% female, 56% rheumatoid factor positive) starting with biological treatment were monitored at treatment start and 3 and 6 months later. Fatigue was assessed with a visual analogue scale (0-10) and disease activity with the erythrocyte sedimentation rate and swollen joint count (28 joints). The intraclass correlation coefficient (ICC) was calculated to examine the extent to which fatigue reflected stable differences between patients. Latent growth curve model analyses examined the level and change of fatigue and disease activity, their association, and the prediction by patient characteristics.
Results Two-third of the variance in fatigue reflected stable individual differences (ICC =0.67); the remaining one-third reflected patients' fatigue fluctuations across time and error variance. Across six months, the mean improvements of fatigue (small effect size, d = -0.43) and disease activity (moderate effect size, d = -0.68) were significant. Latent growth curve model analyses showed that neither stable between-subject differences in fatigue and disease activity were associated nor within-subject changes of fatigue and disease activity. Female gender, younger age, rheumatoid factor negative, and previous use of biologicals predicted a higher fatigue level, but these variables were not correlated with within-subject change of fatigue.
Conclusions Current knowledge suggests that it is most fruitful to target chronic fatigue by means of rehabilitation including life-style adjustment, physical exercise training, and cognitive-behavioral and sleep hygiene education. This fits with our observation and previous observations that RA fatigue is a rather stable individual characteristic that does not give a reflection of steady levels of disease activity. However, contrary to expectation, transient changes in fatigue are also not associated with transient changes in disease activity, which indicates that treatment directed at disease remission is hardly a means to treat fatigue.
Acknowledgements The Society for Rheumatology Research Utrecht (SRU) consists of University Medical Center Utrecht, Antonius Hospital Nieuwegein and Utrecht, Diakonessen Hospital Utrecht, Meander Medical Center Amersfoort, Sint Maartenskliniek Woerden, Hospital St. Jansdal Harderwijk, Tergooi Hospital Hilversum, Flevo Hospital Almere.
Disclosure of Interest None declared