title: Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis.
abstract: BACKGROUND
  Tumor necrosis factor (TNF) is an important mediator of cachexia, and its blockade prevents catabolism in animal models. However, little evidence shows that anti-TNF therapy is effective in treating cachexia in humans.
  
  
  OBJECTIVE
  The main aim of this study was to investigate the effect of etanercept, a synthetic soluble TNF receptor, on body composition in patients with early rheumatoid arthritis (RA).
  
  
  METHODS
  Twenty-six patients were randomly assigned to 24 wk of treatment with etanercept or methotrexate; the latter is the first-line therapy for RA. Body composition, physical function, disease activity, systemic inflammation, and the circulating insulin-like growth factor (IGF) system were measured at baseline (week 0) and at follow-up (weeks 12 and 24). Twelve patients in each treatment group (9 F, 3 M) completed the study.
  
  
  RESULTS
  Overall, no important changes in body composition were observed, despite a transient increase in IGF-I at week 12 (P < 0.01). However, the secondary analysis of those patients (6/treatment group) who gained weight during follow-up showed a significant effect of etanercept on the composition of the weight gained: 44% of weight gained in the etanercept group was fat-free mass, as compared with only 14% in the methotrexate group (P = 0.04). Etanercept and methotrexate were equally effective in controlling the disease and improving physical function.
  
  
  CONCLUSIONS
  Anti-TNF therapy with etanercept is not superior to that with methotrexate for the treatment of rheumatoid cachexia over a period of 6 mo. However, TNF blockade seems to normalize the anabolic response to overfeeding and, if these findings are confirmed, may be useful in conditions characterized by anorexia and weight loss.
authors.affiliation: School of Sport, Health, and Exercise Sciences, University of Wales, Bangor, United Kingdom. s.m.marcora@bangor.ac.uk
authors.forename: Samuele M
authors.initials: SM
authors.lastname: Marcora
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Chester
authors.forename: Gayatri
authors.initials: G
authors.lastname: Mittal
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lemmey
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Maddison
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy; D001823:Body Composition / Q000187:drug effects* / Q000502:physiology; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D015430:Weight Gain
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D000068800:Etanercept; D008727:Methotrexate