Effect of biologics and targeted synthetic disease-modifying anti-rheumatic drugs on fatigue in rheumatoid arthritis

Fatigue is a common and debilitating symptom in patients with RA. Since 2007, fatigue has been included as one of the core outcome measures in RA. Clinical trials of biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have included fatigue as a secondary endpoint. A Cochrane review in 2016 concluded that the bDMARDs have a moderate effect on improving fatigue in RA. More recent clinical trials of the new biologic agent sarilumab and the Janus kinase inhibitors tofacitinib and baricitinib showed similar benefits. It remains unclear whether the effect of bDMARDs and tsDMARDs on fatigue is mediated by direct effects or through a reduction in inflammation. As fatigue was a secondary endpoint, many analyses did not adjust for potential confounding factors, including pain, mood and anaemia, which is a significant limitation.