Fatigue in rheumatoid arthritis
Publication Date
July 17, 2024
Creator
Abstract
Background
Fatigue is a very troublesome symptom in many musculoskeletal diseases. In rheumatoid arthritis (RA), fatigue is one of the most distressing symptoms of the disease. It is not routinely addressed in clinical practice, mainly due to the belief that fatigue is due to chronic inflammation. Fatigue is a core outcome measure in clinical trials and a key symptom whose absence is required to indicate RA remission from the patients’ perspective. However, our knowledge of fatigue remains deficient despite increasing RA fatigue research. A better understanding of fatigue is indicated to facilitate early identification and the development of specific interventions targeted at managing fatigue in people with RA. This study aims to increase our understanding of fatigue in RA by unpicking some of the theorized associations between fatigue and other symptoms in rheumatoid arthritis.
Objectives
1. To determine the prevalence as well as characteristics associated with fatigue in RA
2. To describe the longitudinal course of fatigue and examine heterogeneity in the course of fatigue in RA
3. To describe the prevalence and associations of fatigue in the general population
4. Examine the association between fatigue and central sensitisation in RA
Methods
This thesis presents the result of three observational studies related to fatigue (two in an RA population and the other in the general population) and a primary research study protocol. Data from the early rheumatoid arthritis network (ERAN) (N=1236 at baseline) was used to investigate the prevalence, factors associated with, and course of fatigue in RA. Fatigue was measured with the vitality subscale of the SF36 questionnaire (Vitality), normed to the UK population. Vitality was dichotomised, and age/sex standardised to estimate prevalence at baseline. Correlation and linear regression modelling were used to examine baseline associations. Fatigue progression and heterogeneity were described using hierarchical growth curve and group-based trajectory modelling in participants with three or more Vitality measurements (n=729). Finally, baseline characteristics associated with progression heterogeneity were determined with logistic regression.
The prevalence and associations of fatigue in the general population were described using baseline and one-year follow-up data from the knee pain and related health in the community (KPIC) study, a community-based cohort from the East Midlands, N=9513. Fatigue was measured using the vitality sub-scale of the SF12 questionnaire (SF12VT) and central pain mechanisms by pain detection threshold (PPT) collected from the anterior tibia and sternum in a subgroup of participants. Linear and logistic regression analyses were conducted.
Finally, the study design and development of an observational study to examine the association between central sensitisation, pain and fatigue in RA using a simple questionnaire is presented in this thesis.
Results
The estimated RA fatigue prevalence was 45% (CI: 44% - 50%). Female sex, pain, mental health, and disability were associated with fatigue, explaining about half the variability at baseline (R2 = 0.49). Fatigue remained stable throughout the study period (approximately three years follow-up), exhibiting no clinically significant change. Two distinct fatigue trajectory groups, named ‘fatigue’ and ‘no-fatigue’ groups, were identified in the ERAN cohort. The fatigue group comprised 52.6% of the total population and was associated with female sex, pain, mental health, disability, and comorbidity. The area under the receiver operative characteristic curve (AUROC) was 0.81. Inflammation was not associated with fatigue cross-sectionally or longitudinally.
In the general population, the prevalence of fatigue was 45% (CI:35% - 64%). Fatigue was associated with female sex, pain, depression, anxiety, sleep, and comorbidity at baseline (R2=0.50). Baseline fatigue, pain, depression, sleep, and female sex were associated with fatigue in year one (R2=0.51). A statistically significant association between fatigue and central sensitisation measured PPT was not demonstrated.
Finally, specifics of the study design, role of patient public involvement, ethics application and research quality control in a longitudinal observational study were presented. The study was set up to involve baseline and 12-week assessments of 250 participants with rheumatoid arthritis and aimed to investigate factors associated with fatigue, pain and central sensitisation. Assessment tools included validated self-reported instruments, objective markers of inflammation (laboratory and imaging) and different modalities to assess central sensitisation.
Conclusions
Fatigue still represents an unmet need in rheumatoid arthritis and the general population and remains prevalent and persistent in RA. People with specific traits are more likely to report fatigue and may be identified early in the disease course. This sub-population presents opportunities for individualised care packages and represents a target group for further research.
Fatigue as a patient-reported outcome is a cross-cutting symptom with similar associations in many disease conditions. Therefore, further evaluation outside the context of a specific disease is indicated, as this will encourage active knowledge sharing and facilitate a better understanding of fatigue.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Walsh, David
Keywords
Subjects (LC)
Associated Schools / Departments
School of Medicine
eprints ID
77988
UoN Repository URI
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