Effect of biotherapies on fatigue in rheumatoid arthritis: a systematic review of the literature and meta-analysis

Objectives. To assess the effect of biotherapies vs placebo on fatigue in two situations: inadequate response to conventional treatments (IR-DMARD) and inadequate response to anti-TNF (IR-anti-TNF) in RA. Methods. A systematic review of the literature and meta-analysis were performed. We included randomized controlled trials (RCTs) assessing the effect of biotherapies vs placebo on fatigue, in combination with DMARDs. Fatigue was measured using the functional assessment of chronic illness therapy-fatigue (FACIT-F) or short-form 36 (SF-36) vitality scores at baseline and at Week 24. The results were in effect size (ES) for each biotherapy (or class of biotherapy) vs placebo. An ES of <0.5 was considered as small, between 0.5 and 0.8 as moderate and >0.8 as important. Results. From the 763 published studies, 10 RCTs were included in the analysis: seven involved IR-DMARD RA and three IR-anti-TNF. Among the 3837 included patients with established RA, 1227 patients were treated with an anti-TNF, 420 with rituximab, 258 with abatacept, 205 with tocilizumab and 1727 received placebo. The overall ESs of all biotherapies vs placebo on fatigue were small (ES = 0.45; 95% CI 0.31, 0.58) as well as for anti-TNFs (ES = 0.36; 95% CI 0.21, 0.51). The ESs were small in IR-DMARD RA (ES = 0.38; 95% CI 0.30, 0.46), similar between anti-TNF and non-anti-TNF agents and moderate in IR-anti-TNF RA (ES = 0.57; 95% CI 0.27, 0.86). Conclusion. Few studies reported the impact of biotherapies on fatigue. The effect of biotherapies on fatigue in RA is small.