title: Long-term etanercept therapy favors weight gain and ameliorates cachexia in rheumatoid arthritis patients: roles of gut hormones and leptin.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNF-α therapy on body weight, appetite, plasma gut hormones and leptin have not been investigated.
  
  
  METHODS
  Twenty RA patients received subcutaneous injections of etanercept, a chimeric protein of human IgG1 Fc and TNF receptor p75, twice weekly for 12 consecutive months. Sequential changes in body weight, body fat, appetite rating, lipid profiles, gut hormones and leptin were measured at baseline and at 3 and 12 months after treatment. Ten RA patients who received non-biological disease modifying anti-rheumatic drugs were enrolled as the controls and were appraised at baseline and at 12 months after treatment (a nonrandomized study).
  
  
  RESULTS
  Significant weight gain, hyperuricemia, decreased fasting plasma glucose-dependent insulinotropic polypeptide (GIP) levels, and loss of post-oral glucose suppression of plasma leptin concentration were found in the patients after the 12-month course of etanercept therapy, but not in the controls. A transient decrease in fasting plasma acyl ghrelin occurred at 3 months during etanercept treatment. Appetite score and serum lipid profiles did not change in either group.
  
  
  CONCLUSIONS
  Long-term therapy with anti-TNF-α is promising in ameliorating body mass decrease in patients with active RA. Plasma levels of ghrelin, GIP and leptin may play significant roles in maintaining energy homeostasis in the anti-inflammatory responses during RA remission.
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. chency@vghtpe.gov.tw
authors.forename: Chih-Yen
authors.initials: CY
authors.lastname: Chen
authors.forename: Chang-Youh
authors.initials: CY
authors.lastname: Tsai
authors.forename: Pui-Ching
authors.initials: PC
authors.lastname: Lee
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001066:Appetite / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D001823:Body Composition; D015992:Body Mass Index; D002100:Cachexia / Q000209:etiology / Q000517:prevention & control*; D000068800:Etanercept; D005260:Female; D005768:Gastrointestinal Hormones / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use*; D020738:Leptin / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D018501:Antirheumatic Agents; D005768:Gastrointestinal Hormones; D007074:Immunoglobulin G; D020738:Leptin; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept