For patients with rheumatoid arthritis (RA), biological interventions of both anti-tumor necrosis factor (anti-TNF) and non-anti-TNF agents may lead to a small to moderate improvement in fatigue.
By conducting a search of 14 large-scale electronic databases, researchers identified 32 randomized controlled trials that evaluated biological interventions in RA patients, who self-reported fatigue in outcome measures. In total there was 14,628 individuals in the analysis, 9,946 received biologics and 4,682 received standard disease-modifying anti-rheumatic drug (DMARDs) therapy. Twenty of the studies examined anti-TNF biologics and 12 examined non-anti-TNFs.
The trials used a variety of methods to measure fatigue outcomes (Functional Assessment of Chronic Illness Therapy Fatigue Domain [FACIT-F], Short Form-36 Vitality Domain [SF-36 VT], Visual Analogue Scale [VAS] [0 to 100 or 0 to 10] and the Numerical Rating Scale [NRS]), so researchers calculated standardized mean differences (SMD).
Results showed that treatment with biologic agents led to a significant reduction in fatigue with a SMD of –0.43 (95% CI –0.49 to –0.38; P<0.00001). Reductions were similar between types of biological therapies with a SMD of –0.42 (95% CI –0.49 to –0.35, P<0.00001) and –0.46 (95% CI –0.53 to –0.39; P<0.00001) for anti-TNF and non-anti-TNF, respectively. Although significant heterogeneity was noted in the anti-TNF trials (I2=54%, P=0.0002), which may have been due to difference dosage, participant characteristics, previous treatment and comorbidities associated with fatigue.
The authors acknowledge that the instruments used to measure fatigue were not developed specifically for that reason in RA. However, they have been validated for assessing fatigue for other medical conditions. The findings of this study support findings from a smaller trial (Chauffier 2012) which included an analysis of just 10 trials.
Currently, there is no consensus on the most effective management approaches to fatigue in RA, and while these results indicated positive signs with biologics the authors conclude that, “It is unclear whether the improvement results directly from the biologic interventions on fatigue or indirectly through reduction in inflammation and disease activity.”
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