Abstract

BackgroundFatigue is common among patients with rheumatoid arthritis (RA) with a substantial impact on quality of life (1). Biological disease-modifying antirheumatic drugs (bDMARDs) have been shown to significantly improve fatigue in these patients. However, fatigue is under-assessed by the physicians and evidence is still scarce regarding a possible impact of fatigue on disease activity over time.ObjectivesTo explore the long-term impact of fatigue on the disease activity in patients with RA treated with bDMARDs.MethodsA monocentric observational retrospective cohort study was conducted with 24 months (M) of follow-up. Patients diagnosed with RA, according to the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria, and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first bDMARD between 2015 and 2021 were included. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. Fatigue was monitored at baseline, 12 and 24M using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). This scale is a 13-item self-reported questionnaire with a total score ranging from 0 to 52. A score ≤ 39 indicates the presence of clinically significant fatigue. Disease Activity Score for 28 joints with erythrocyte sedimentation rate (DAS28), DAS28 with C-reactive Protein (CRP) [DAS28-CRP], DAS28 delta, Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) were calculated to measure disease activity. Clinical response was evaluated by EULAR criteria in three response categories- good, mild and no response- and by ACR criteria (0 to 100%) at 12 and 24M. To correlate fatigue score with EULAR clinical response Chi-square test was used. Multivariate linear regression models adjusted for age, gender and disease duration were used to assess the effect of fatigue on disease activity and ACR clinical response over time.ResultsA total of 40 patients with RA were included, with a mean age of 47.4±11.4 years old and disease duration of 10.4±5.6 years. Most patients were female (90.2%). Rheumatoid Factor was positive in 70% of patients. The majority of patients (85%) had clinically significant fatigue at baseline moment (FACIT-F 26.9±11.8). Treatment characteristics and baseline disease activity scores are described in Table 1. Fatigue at baseline moment predicted DAS28(CRP) (β=-0.061, 95%CI [-0.12; -0.003]) and CDAI (β=- 0.30, 95%CI [-0.57; -0.029]) at 12M. Additionally, fatigue predicted SDAI (β=-0.38, 95%CI [-0.72; -0.047]) and CDAI (β=- 0.39, 95%CI [-0.73; -0.051]) at 24M. In general, for these models, fatigue as a symptom was shown to have negative effects on the different outcomes analysed. Fatigue did not associate with EULAR and ACR responses over time.Table 1.Baseline characteristics of sample. LEGEND: SD: Standard deviation; DAS28: Disease Activity Score for 28 joints; CRP: C-reactive Protein; CDAI: Clinical Disease Activity Index; SDAI: Simplified Disease Activity Index.VariableDescriptive statisticTreatment optionsn(%)Glucocorticoids37(92.5)Conventional DMARDs37(92.5)Anti-TNF19(47.5)Etanercept13(32.5)Rituximab4(10)Tocilizumab4(10)Disease activity scoreMean±SDDAS285.4±0.87DAS28-CRP4.9±0.69CDAI27.6±8.5SDAI28.9±8.7ConclusionThese findings showed that, in our sample, the most RA patients had severe fatigue and its presence may be a predictor of increased disease activity. Indeed, previous research observed a positive association between fatigue and disease activity over the time in patients with RA (2). Therefore, fatigue should be regularly monitored in patients with RA and its impact on treatment must be considered. Moreover, further research with larger samples is needed to explore the impact of fatigue on clinical response and the potential of fatigue relief as an outcome measure of RA treatment.

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