Along with the joint pain, stiffness, and swelling that characterize rheumatoid arthritis (RA), many patients have a range of other symptoms that affect their overall disease burden and quality of life. Fatigue is one of the most common symptoms among individuals with RA, with prevalence rates of 40%-80% observed in this population. Patients have identified fatigue as one of the most important disease outcomes in RA, and the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group has recommended that all RA studies include fatigue as an outcome domain.1

Fatigue can interfere with personal relationships and activities of daily living. An estimated 36%-44% of role limitations in RA have been attributed to fatigue, as well as 64% of mental health symptoms and 52%-57% of problems with physical and social functioning.1 Patients have indicated that work disability is one of the most significant consequences of fatigue. A longitudinal study linked fatigue in RA to activity impairment (odds ratio [OR], 1.52; 95% CI, 0.79-2.26), loss of work productivity (OR, 4.16; 95% CI, 2.47-5.85), and a greater likelihood of absenteeism (OR, 1.23; 95% CI, 1.02-1.49).2

In addition, fatigue has been found to account for 51% of the general perception of health worsening in RA patients.1 Regardless of the level of inflammatory control, patients are likely to perceive their disease activity unfavorably in the presence of persistent fatigue. Fatigue is reportedly the main driver of patient global assessment, which “has a significant weight in current disease activity indices used to guide treatment decisions, thus conveying an indirect impact of fatigue in heightened medication cost and risk of overtreatment,” wrote Santos et al in a paper published in November 2019 in Rheumatology.1

Despite the substantial role of fatigue in RA, there is currently no recommended gold standard instrument for measuring this symptom or its impact. While fatigue was previously viewed as stemming from disease activity in RA, findings from recent studies “support a multifactorial aetiology for fatigue, involving an array of co-morbid factors, such as disability, psychological well-being, social support” and others, according to the authors.1 Thus, the accurate assessment of fatigue in RA presents multiple challenges. 


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Validated instruments to measure RA fatigue

Santos et al examined the instruments that are most often used by researchers and clinicians to measure fatigue in RA and which have adequate evidence of validation for this specific purpose. They found that the following 12 instruments meet these criteria and may be used to measure RA fatigue, with selection depending on the setting and the purpose of assessment in each case:

  • Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF MDQ);
  • Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scales (BRAF NRS) for severity, effect, and coping;
  • Chalder Fatigue Questionnaire (CFQ);
  • Checklist Individual Strength (CIS20R and CIS8R);
  • Functional Assessment Chronic Illness Therapy, Fatigue (FACIT-F);
  • Fatigue Severity Scale (FSS);
  • Multi-Dimensional Assessment of Fatigue (MAF);
  • Multi-Dimensional Fatigue Inventory (MFI);
  • Profile of Mood States (POMS);
  • Rheumatoid Arthritis Impact of Disease Fatigue Subscale (RAID-F);
  • Short Form 36 Vitality Subscale (SF-36 VT); and
  • Visual Analogue Scales (VAS).

While debate continues regarding the benefits of using disease-specific vs generic instruments and multi-item/multidimensional vs single-item assessments in measuring RA fatigue, the authors emphasized the importance of assessing the “impact triad” of the severity, importance, and self-management of fatigue from the patient’s perspective.1 This triad was a consideration in the development of the BRAF NRS.3

When appropriate in clinical practice, they suggest using a single-item instrument such as the BRAF NRS or the RAID-F as a screening tool, followed by multidimensional assessments if significant levels of fatigue are detected on screening. “Given the multifactorial nature of fatigue, it may be wise to measure other domains of significant impact for patients” such as pain, functional disability, and sleep disturbances, for which intervention may lead to reduced fatigue levels.1

Currently, Santos et al recommend the Rheumatoid Arthritis Impact of Disease Score (RAID) as the optimal instrument to be used for this purpose. The RAID assesses 7 domains of impact (pain, functional disability, fatigue, emotional well-being, physical well-being, sleep, and coping) to produce a composite score. Using the separate scores of each domain (RAID.7i) provides a “feasible tool to analyse impact of disease and to design and monitor individually tailored interventions, targeting the domains of concern, and thus indirectly improving fatigue,” they noted.1,4

For additional insights, we interviewed Janet E Pope, MD, MPH, FRCPC, professor of medicine in the division of rheumatology at the University of Western Ontario Schulich School of Medicine, and head of rheumatology at St. Joseph’s Health Care in London, Ontario, Canada. Dr Pope has co-authored several recent papers pertaining to fatigue in RA.5-8

Fatigue is a very common symptom in RA, as is pain. Both fatigue and pain may be related to disease activity but can become chronic and fixed even if disease activity is reduced and/or the person is in remission. We do know that in early RA, optimal improvement in fatigue lags behind other outcomes such as swollen joints by approximately 6 months.5 If a person has chronically disrupted sleep due to pain, inflammation, fear, anxiety, and so on, you can’t get them better overnight. The relationship between fatigue and RA disease activity has a very low correlation, so fatigue is multifactorial.6 

We need to address patients’ concerns regarding fatigue. Good sleep hygiene is important – for example, going to bed at the same time each night, exercising but not right before bed, avoiding alcohol and caffeine later in the day, turning screens off well before bed, and sleeping in a cool, quiet room. There are helpful online apps including meditation, deep breathing, and other “tricks” that may enhance sleep. Trying to avoid sleeping pills is a good idea, as they don’t lead to deep restorative sleep. If medications are needed, low-dose amitriptyline may be helpful. Pacing and exercise may help.

If someone can’t sleep after about 45 minutes, they should get up and do something such as read a book. Use the bed and bedroom for sleep, not work. I think acknowledging the problem and admitting there are not great solutions does help the patient. Also, give the patient homework to help with their sleep, letting the patient take control and explore the options. Look for other causes of fatigue that may be treated differently such as sleep apnea, depression, and anemia. Try to avoid narcotics if a person has pain, as they can contribute to fatigue. 

What are other relevant considerations for clinicians regarding this topic, and what are remaining needs in this area?

Evidence-based treatment of fatigue in RA is not great, so borrow ideas from fatigue in other conditions. We need to find treatments for fatigue that are unrelated to RA flares/inflammation. The fatigue can be a big enough problem to cause work disability and poor function. 

References

  1. Santos EJF, Duarte C, da Silva JAP, Ferreira RJO. The impact of fatigue in rheumatoid arthritis and the challenges of its assessment. Rheumatology (Oxford). 2019;58(Suppl 5):v3-v9. doi:10.1093/rheumatology/kez351
  2. Druce KL, Aikman L, Dilleen M, Burden A, Szczypa P, Basu N. Fatigue independently predicts different work disability dimensions in etanercept-treated rheumatoid arthritis and ankylosing spondylitis patients. Arthritis Res Ther. 2018;20(1):96. doi:10.1186/s13075-018-1598-8
  3. Sanderson TC, Hewlett SE, Flurey C, Dures E, Richards P, Kirwan JR. The impact triad (severity, importance, self-management) as a method of enhancing measurement of personal life impact of rheumatic diseases. J Rheumatol. 2011;38(2):191-194. doi:10.3899/jrheum.100700
  4. Gossec L. Domains of health important for rheumatoid arthritis patients can be assessed separately: reliability and responsiveness of the Rheumatoid Arthritis Impact of Disease Score – 7 items (RAID.7i). Vivli Center for Global Clinical Research Data. Accessed online January 29, 2021.
  5. Pope JE. Management of fatigue in rheumatoid arthritis. RMD Open. 2020;6(1):e001084. doi:10.1136/rmdopen-2019-001084
  6. Holdren M, Schieir O, Bartlett SJ, et al; Canadian Early Arthritis Cohort investigators. Improvements in fatigue lag behind disease remission in early rheumatoid arthritis: results from the Canadian Early Arthritis Cohort. Arthritis Rheumatol. 2021;73(1):53-60. doi:10.1002/art.41499
  7. Pope JE, Rampakakis E, Movahedi M, Cesta A, Sampalis JS, Bombardier C. Time to remission in swollen joints is far faster than patient reported outcomes in rheumatoid arthritis: results from the Ontario Best Practices Research Initiative (OBRI). Published online August 13, 2020. Rheumatology (Oxford). doi:10.1093/rheumatology/keaa343
  8. Michaud K, Pope J, van M, et al. A systematic literature review of residual symptoms and unmet need in patients with rheumatoid arthritis. Published online July 3, 2020. Arthritis Care Res (Hoboken). 2020. doi:10.1002/acr.24369