A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis.

摘要: OBJECTIVE: To assess the pharmacokinetics, safety profile, and efficacy of fully human anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody adalimumab (D2E7) in patients with long-standing, active rheumatoid arthritis (RA). METHODS: This was a randomized, double blind, placebo controlled study single intravenous injections ascending doses (0.5 to 10 mg/kg) 5 cohorts 24 each (18 6 all except 0.5 mg/kg cohort 17 adalimumab, 7 placebo). A total 120 participated (adalimumab 89, 31). The clinical response measured by changes composite scores defined criteria European League Against Rheumatism (EULAR) American College Rheumatology. RESULTS: Single showed rapid onset effect (24 hours 1 week), peak at 2 weeks that sustained for least 4 as long 3 months some patients. EULAR seen once during week period after drug injection 29% group well 41%, 78%, 72%, 89%, 100% 0.5, 1, 3, 5, groups, respectively. No dose related increases adverse events were observed compared group. Adalimumab systemic exposure (AUC0-( )) increased linearly an increase dose. mean serum clearance 0.012 0.017 l/h, steady-state volume distribution ranged from 4.7 5.5 l. estimated terminal half-life 10.0 13.6 days cohorts, overall 12 days. CONCLUSION: Treatment Mab safe tolerated when administered up mg/kg, associated clinically significant improvement signs symptoms RA.