Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis.
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.
Marcora
Samuele M
SM
School of Sport, Health, and Exercise Sciences, University of Wales, Bangor, United Kingdom. s.m.marcora@bangor.ac.uk
Chester
Kathryn R
KR
Mittal
Gayatri
G
Lemmey
Andrew B
AB
Maddison
Peter J
PJ
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
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