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)-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. 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.