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

作者：Chen Der Yuan; Lai Ning Sheng; Lu Ling Ying; Chou Hsiu Cheng; Chen Yi Hsing; Hsieh Tsu Yi; Chen Yi Ming; Lan Joung Liang^*

来源：Journal of the Chinese Medical Association, 2011, 74(12): 544-551.

DOI：10.1016/j.jcma.2011.10.009

• efficacy
• immunology
• RA
• rheumatoid arthritis
• TNF-alpha
• tumor necrosis factor
• TuNEX

Background: Tumor necrosis factor (TNF)-alpha is a pivotal inflammatory cytokine in the pathogenesis of rheumatoid arthritis (RA). TuNEX, a recombinant TNE-alpha receptor protein, can effectively bind TNF-alpha. The purpose of this phase I/III 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.
Conclusion: 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.

• 出版日期2011-12