title: Effect of biotherapies on fatigue in rheumatoid arthritis: a systematic review of the literature and meta-analysis.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Few studies reported the impact of biotherapies on fatigue. The effect of biotherapies on fatigue in RA is small.
authors.affiliation: Department of Rheumatology, Pierre and Marie Curie University Paris VI, Saint-Antoine Hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Chauffier
authors.forename: Carine
authors.initials: C
authors.lastname: Salliot
authors.forename: Francis
authors.initials: F
authors.lastname: Berenbaum
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha