title: A multicenter open-label phase I/II study to assess the safety, tolerability, and efficacy of three dose levels of TuNEX in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Tumor necrosis factor (TNF)-α is a pivotal inflammatory cytokine in the pathogenesis of rheumatoid arthritis (RA). TuNEX, a recombinant TNF-α receptor protein, can effectively bind TNF-α. The purpose of this phase I/II dose-escalation study was to assess the safety and preliminary efficacy of three dose levels of TuNEX in Taiwanese patients with RA.
  
  
  METHODS
  Eighteen patients with active RA from three medical centers who had failed previous therapy with at least one disease modifying antirheumatic drug (DMARD) were enrolled. The primary efficacy endpoint was a 20% improvement in the American College of Rheumatology criteria (ACR20) in the fourth week. The occurrence of treatment-emergent adverse events (TEAEs) was the primary safety variable.
  
  
  RESULTS
  The highest percentage of TuNEX 25-mg- and 35-mg-treated patients achieved an ACR20 response (60% and 100%, respectively) for the first time at Week 2 during the 4-week treatment period. There was a strong trend toward a superior ACR20 response rate in the TuNEX 15-mg group (83.3%) in comparison with the TuNEX 25-mg group (40.0%) and the TuNEX 35-mg group (50.0%) at week 4. Patients who received 15-mg TuNEX, 25-mg TuNEX, and 35-mg TuNEX had 35.99%, 16.85%, and 21.86% reduction of disability indices of Health Assessment Questionnaire after drug treatment, respectively. The most commonly reported adverse event was injection-site reaction. The TEAEs were comparable between the three TuNEX-treated groups.
  
  
  CONCLUSIONS
  TuNEX reduced the signs and symptoms of RA and improved physical function, with clinically acceptable safety and tolerability in patients who had previously received DMARDs.
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.forename: Ning-Sheng
authors.initials: NS
authors.lastname: Lai
authors.forename: Ling-Ying
authors.initials: LY
authors.lastname: Lu
authors.forename: Hsiu-Cheng
authors.initials: HC
authors.lastname: Chou
authors.forename: Yi-Hsing
authors.initials: YH
authors.lastname: Chen
authors.forename: Tsu-Yi
authors.initials: TY
authors.lastname: Hsieh
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.forename: Joung-Liang
authors.initials: JL
authors.lastname: Lan
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; C571708:TuNEX protein