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

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. Copyright (C) 2011 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.