Fatigue Still Persists Long After Arthritic Flares Subside


New treatments for rheumatoid arthritis can effectively control inflammation, but they do little to improve quality of life indicators-like fatigue-that are important to patients, shows a new study.

Fatigue Still Persists Long After Arthritic Flare Subsides


A study of 2,701 early rheumatoid arthritis (RA) patients finds that even though patients may achieve low disease activity and experience statistically significant improvements in DAS28 and ESR after five years of treatment, the visual analog scale (VAS) and the Mental Component Scores of Short Form 36 suggests improvements are not statistically significant-to the patient. The study appears in this month’s issue of Rheumatology.

In this study, led by Sam Norton, Ph.D., of King’s College London, researchers compared the progression of disease to functional disability and health-related quality of life (HRQoL) measures from two studies going back 30 years.

“This study demonstrates improvements in inflammatory markers over time in early RA [are] in line with improved treatment strategies. [But] these have not translated into similar improvements in patient-reported outcomes relating to either physical or mental health,” researchers wrote.

While the presence of inflammation in early rheumatoid arthritis has declined over the last three decades due to newer effective treatments, patients still feel the effects of disease, in particular, mental health effects, functional disability, pain, and fatigue. 

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Plus, while newer treatments can increasingly control disease activity, they don’t appear to have had the same impact on the presence of comorbidities, such as cardiovascular disease and obesity which continue persist in early RA and RA patient populations.

“It is likely that adoption of more intensive and aggressive treatment strategies are the primary drivers for the decline in inflammatory markers of the disease, it is unclear whether the increases in comorbidities and obesity are hampering equal improvements in pain, fatigue and functional disability,” Norton et al. wrote.

Now that effective treatments for inflammatory arthritis exist, the healthcare community should focus on treatments for comorbidities that may increase the risk of morbidity and mortality, researchers wrote.


The study is based on a review of records from the Norfolk Arthritis Register (NOAR) which followed patients with early rheumatoid arthritis for five years.

Patients who were recruited between 2000-2004 experienced significant improvements in disease activity as compared to patients treated between 1990 and 1994. The improvements, according to researchers, were due to the use of methotrexate as an anchor DMARD, the introduction of biologic DMARDs and the adoption of treat-to-target treatment. However, the treatments did little to improve functional disability, “and therefore it is unclear whether these improvements in disease activity have translated into improvements in key PROs, such as mental health, fatigue and pain.”

Statistically significant improvements in both 28-joint count DAS and ESR were documented over the five years in patients diagnosed with RA compared to patients who were diagnosed earlier.
After five years of treatment, 59 percent of patients diagnosed in 2010 were expected to achieve low disease activity as compared to 48 percent of those diagnosed in 2002 and 32 percent diagnosed in 1990.

Improvements in HAQ were statistically significant, but small. The visual analog scale (VAS) and the Mental Component Scores of the Short-Form 36 showed similar, statistically non-significant levels over the five years for each time period.

Patients treated with anti-TNF inhibitors experienced statistically and clinically significant reductions in fatigue but achieving disease remission did little to improve fatigue for most patients.

“There is a clear need to examine the subjective aspects of the disease, which is driving the discordance between objective measures of inflammation, and the patient-reported measures. Greater incorporation of PRO in both clinical research and practice is vital, as they measure important aspects of the disease not currently assessed in standard disease activity measures,” the authors wrote.

Lewis Carpenter, Elena Nikiphorou, Patrick D W Kiely, et al. “Secular changes in the progression of clinical markers and patient-reported outcomes in early rheumatoid arthritis.” Rheumatology. January 3, 2020. doi.org/10.1093/rheumatology/kez635

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