Although fatigue is common in rheumatoid arthritis (RA), many patients still receive inadequate support to appropriately address this issue.1
According to the results of a survey conducted by the National Rheumatoid Arthritis Society,2 51% of 2029 respondents never or rarely spoke to their primary care physician about fatigue symptoms; in a similar fashion, 47% never or rarely discussed this issue with their rheumatologist or specialist nurse, and a staggering 79% reported that their fatigue level was never measured by their physician.
“RA fatigue appears to be a complex and multi-factorial phenomenon and while a conceptual model has been proposed, the precise mechanisms and causality remain unclear,” wrote Fiona Cramp, PhD, faculty of health and applied sciences at the University of the West of England in Bristol, United Kingdom, in a 2019 review article published in Rheumatology.1 Predictors of fatigue in RA, she added, are reported to include inflammation, cognitive behavioral elements, and personal factors such as work and support networks.1
Dr Cramp noted that even optimal pharmacologic management of RA provides only a small benefit for reducing fatigue, typically through indirect means, including the reduction of pain and inflammation.1 Conversely, nonpharmacologic management may alter causal pathways of fatigue and provide a larger benefit.1 Dr Cramp outlined these management methodologies in her narrative review and examined recent evidence to quantify the role of various interventions in the management of fatigue.
Cochrane Review Results
A 2013 Cochrane review3 evaluated both the benefits and harms of nonpharmacologic interventions for fatigue management in RA. The review utilized relatively broad inclusion criteria, allowing any randomized controlled trial to be included if it assessed a nonpharmacologic intervention in patients with RA and had fatigue as a primary or secondary outcome.3
Both physical activity and psychosocial interventions were found to potentially benefit fatigue management in people with RA.3 However, adverse events were not reported in any of the included studies, preventing accurate assessment of potential harms, and overall evidence quality was considered low to moderate.³ The review authors recommended the creation of interventions specifically for fatigue management in RA and the development of high-quality trials to assess these interventions and their cost-effectiveness. They also noted that the lack of a self-reported fatigue measurement system validated specifically for the RA population may have contributed to the mixed results in existing literature.3
In the time since the Cochrane review’s publication, ample new evidence has been published on the topic of fatigue management in RA.4-10
In Dr Cramp’s narrative review, 6 studies that identified fatigue as either the primary or joint primary outcome were discussed, with 4 studies focusing only on patients who experienced significant fatigue.1 Consistency across studies in terms of measurements used to assess fatigue was lacking; studies used the Fatigue Severity Scale,7,10 a visual analog scale,4,6 a numerical rating scale,8 a patient-reported outcome measurement information system (the Fatigue Short Form),5 a multidimensional fatigue inventory,4 and the Checklist Individual Strength.9 Dr Cramp also noted that it was not apparent whether all interventions had been designed specifically to target fatigue reduction.
Research Results in Brief
Within the 4 studies focusing on physical activity interventions, 3 identified fatigue as either a primary or joint primary outcome. One study7 that investigated a home exercise plan was individualized to target participant-identified functional limitations; however, this study made no reference to fatigue mechanisms in either the design or implementation of the intervention. Another study5 that employed a pedometer intervention had the goal of increasing participant physical activity.
A third study⁶ examined the use of a person-centered physical therapy intervention, focused on health-enhancing physical activity and balanced lifestyle activities. The investigators suggested that this approach might both strengthen confidence and help manage fatigue as well as disease-related, fatigue-associated symptoms.
Overall, 3 of the 4 studies4,6,7 reported significant improvements in fatigue at the end of each respective intervention compared with the control groups. In the fourth study,5 researchers demonstrated a fatigue reduction in both groups that received pedometers to record daily step count, but outcomes were not significantly different from control group outcomes.
Two studies examining psychosocial interventions8,9 also included fatigue as a primary or joint primary outcome. The first⁸ examined RA fatigue management by using cognitive behavioral therapy approach to address “[behaviors] likely to be related to fatigue and their underpinning thoughts and feelings.”8 The second study9 involved participants completing at least 1 of 4 internet-based cognitive behavioral intervention modules; however, not all participants completed a module focused on fatigue. Although the fatigue module did include “relevant cognitive and behavioral strategies,”1 the overall purpose of the intervention was focused on general reduction of distress.9
Researchers reported significant reductions in fatigue impact at 6 months in the intervention group compared with the control group in the first study.8 At 2-year follow up, this difference remained significant. These results, Dr Cramp noted in her narrative review, “[add to] the findings from the Cochrane review [and support] the use of [cognitive behavioral therapy] approaches for fatigue management in RA.”1 Conversely, results of the second study9 showed a nonsignificant reduction in fatigue over time in patients who participated in the internet-based interventions compared with participants in the control group.
Aromatherapy and Reflexology
One study10 examined aromatherapy and reflexology interventions, with change in fatigue as a joint primary outcome. For the aromatherapy domain, oils were identified by their active ingredients and proposed physiologic effects. For the reflexology domain, investigators described the specific points being stimulated, but not how these points were relevant to the management of fatigue.
Investigators identified significant reductions in fatigue for both intervention groups compared with the control group, although patients in the reflexology group experienced a greater reduction.10 Limitations of the study included a lack of assessor blinding, the absence of long-term follow-up, and having no active control group.1 As such, further research is necessary before either method can be recommended as an intervention to improve fatigue in RA.
Looking to the Future
Several different disease-specific mechanisms have been proposed to explain any beneficial effects of nonpharmacologic interventions for fatigue in RA. High-intensity exercise, for example, restores muscle mass and function in RA, reducing the effort required to carry out physical tasks.1 Regular participation in moderate- to high-intensity exercise may improve patient self-efficacy, wellbeing, and provide a sense of control for patients with RA, and educational programs may help patients change behaviors that perpetuate RA fatigue or inhibit disease self-management.1
Despite these positive outcomes, barriers to delivery in clinical practice should also be considered, according to Dr Cramp, who noted that a majority of the psychosocial interventions assessed in existing literature were delivered by clinical psychologists. This delivery method creates barriers in clinical practice because of the small number of rheumatology teams that include clinical psychology staff. However, study findings also indicate that these interventions can be successfully delivered by other rheumatology team members, including nurses and occupational therapists, with proper training.1
“The findings from these seven studies provide further evidence that physical activity and psychosocial interventions provide small to moderate benefit in relation to self-reported fatigue in adults with RA,” Dr Cramp wrote,1 adding that further research is necessary to confirm the effectiveness of psychosocial interventions not based on cognitive behavioral therapy, and that future efforts may benefit from a “more consistent approach to assessment of fatigue.”
“While limitations remain in relation to the evidence to support the use of non-pharmacological interventions in the management of RA-related fatigue, it is clear that they have the potential to benefit,” Dr Cramp concluded.1
Disclosure: The supplement authored by Dr Grant was supported by a grant from Gilead Sciences, Inc. Please see the original references for a full list of disclosures.
1. Cramp F. The role of non-pharmacological interventions in the management of rheumatoid arthritis-related fatigue. Rheumatology. 2019;58(suppl 5):v22-v28.
2. National Rheumatoid Arthritis Society. Invisible disease: rheumatoid arthritis and chronic fatigue. Published 2014. Accessed April 9, 2020. https://www.nras.org.uk/invisible-disease-rheumatoid-arthritis-and-chronic-fatigue-survey
3. Cramp F, Hewlett S, Almeida C, et al. Non-pharmacological interventions for fatigue in rheumatoid arthritis. Cochrane Database Syst Rev. 2013;8:CD008322.
4. Thomsen T, Aadahl M, Beyer N, et al. The efficacy of motivational counseling and SMS reminders on daily sitting time in patients with rheumatoid arthritis: a randomised controlled trial. Ann Rheum Dis. 2017;76(9):1603-1606.
5. Katz P, Margaretten M, Gregorich S, Trupin L. Physical activity to reduce fatigue in rheumatoid arthritis: a randomized controlled trial. Arthritis Care Res. 2018;70(1):1-10.
6. Feldthusen C, Dean E, Forsblad-d’Elia H, Mannerkorpi K. Effects of person-centered physical therapy on fatigue-related variables in persons with rheumatoid arthritis: a randomized controlled trial. Arch Phys Med Rehabil. 2016;97(1):26-36.
7. Durcan L, Wilson F, Cunnane G. The effect of exercise on sleep and fatigue in rheumatoid arthritis: a randomized controlled study. J Rheumatol. 2014;41(10):1966-1973.
8. Hewlett S, Almeida C, Ambler N, et al; on behalf of the RAFT Study group. Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural therapy approaches by rheumatology teams (RAFT). Ann Rheum Dis. 2019;78(4):465-472.
9. Ferwerda M, van Beugen S, van Middendorp H, et al. A tailored-guided internet-based cognitive-behavioral intervention for patients with rheumatoid arthritis as an adjunct to standard rheumatological care: results of a randomized controlled trial. Pain. 2017;158(5):868-878.
10. Gok Metin Z, Ozdemir L. The effects of aromatherapy massage and reflexology on pain and fatigue in patients with rheumatoid arthritis: a randomized controlled trial. Pain Manag Nurs. 2016;17(2):140-149.