Biologics and Fatigue in Rheumatoid Arthritis Save

Researchers from Bristol, UK have published a Cochrane review studying the effects of biologic therapies on fatigue. Based on a review of the electronic literature and randomised controlled trials they found that biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue.

Fatigue is a common and bothersome symptom for patients with rheumatoid arthritis (RA) and other inflammatory disorders.  Despite its importance to patients, there is no known best approach to managing fatigue, other than to control the underlying disorder.

Researchers identified 20 studies of the anti-TNF agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on non-TNF biologics (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). These studies added either biologics or placebo to background DMARD therapy.

These studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue (as measured by validated objective instruments). To reported pooled data calculated from standard mean differences

Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of -0.43 (95% confidence interval (CI) -0.38 to -0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52).

Both TNF and non-TNF biologic agents achieved a similar level of improvement ((-0.42 vs -0.46) by week 24. None of these studies assessed long-term changes in fatigue.

Despite these modest findings, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or other mechanisms.

Another group of investigators from Aberdeen, UK assessed fatigue as one of many outcomes from the British Society for Rheumatology Biologics Register (BSRBR) for RA. They found that although their biologic patients achieved clinical remission, many RA patients in remission do not achieve complete remission of their fatigue. Hence, signficant reductions in disease activity may not always associated with a commensurate reduction in fatigue.

One difference in this study was that fatigue was assessed using the SF-36 (36-item Short Form Health Survey) vitality score ⩽12.5 and that disease activity was assessed by DAS28 <2.6 at a 24 week time point.  

Severe baseline fatigue (SF-36 vitality score ⩽12.5) was found in 2652 patients from the BSRBR registry.  Only one-third (37.3%) of those who achieved DAS28 remission at 6 mos. also achieved fatigue remission.  Such patients had clinically poorer health status, hypertension, depression, stroke and baseline treatment with steroids and antidepressants.

These authors believe that fatigue may not be uniquely tied to inflammation or disease activity and that specific management approaches may be need for those with fatigue, especially if it does not resolve. 

In summary, fatigue is highly important to patients.  The challenge comes in the origins of fatigue and how to best manage them.  While fatigue is clearly linked to inflammation and disease activity in many RA patients, there are others whom will continue despite disease control.  Fatigue may also result from poor sleep, depression, chronic pain, endocrinopathies, anemia or other systemic illnesses and may need separate evaluation and treatment.