Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: A pilot study

摘要: Abstract Background: Because traditional therapies for rheumatoid arthritis (RA) such as methotrexate (MTX) do not produce an adequate response in many patients, newer that block the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) are increasingly being used combination with MTX. Objective: This study evaluated efficacy, pharmacokinetics, and safety profile of adalimumab, a fully human anti-TNF alpha monoclonal antibody, when added to continuing MTX therapy. Methods: Phase I, randomized, dose-titration consisted 4-week, double-blind, placebo-controlled treatment phase 26-month, open-label continuation phase. Patients RA who had been taking stable doses (mean dose, 17 mg/wk) ≥3 months before enrollment inadequate were randomly assigned receive 2 single either adalimumab 0.25, 0.5, 1, 3, or 5 mg/kg IV placebo double-blind In phase, patients received 1 every other week monthly 18 months; then switched 40 mg SC monthly. The main efficacy end point was 20% improvement American College Rheumatology criteria (ACR20). Other points included 50% (ACR50) 70% improvements ACR criteria. Pharmacokinetic parameters analyzed during both phases study. Serum concentrations using validated enzyme-linked immunosorbent assay relying on double-antigen principle. Peak trough determined from observed concentration-time data, modeling approach estimate total serum clearance, mean apparent terminal half-life, volume distribution at steady state, area under curve. Results: Sixty entered 45 receiving 15 placebo; recipient chose continue into Overall, population 47 (78.3%) women 13 (21.7%) men. age 52.9 years (range, 24–73 years), body weight 69.7 kg 43–98 kg). ACR20 ACR50 responses achieved least assessment 4-week by respective 29 (64.4%) 11 (24.4%) active 4 (26.7%) none placebo. Responses rapid, 10 (22.2%) achieving within 24 hours dosing. Of recipients response, (62.1%) duration (time first occurrence nonresponse) weeks, (37.9%) 3 weeks. pharmacokinetic properties appeared be linear. half-life after intravenous dose ranged 19 days groups. Repeated administration no statistically significant effect pharmacokinetics MTX, indicating adjustment is necessary. Adalimumab well tolerated, there dose-related adverse events. Conclusions: Among addition significant, long-term compared plus ( P ≤ 0.05), indicated 26 months. tolerated. exhibited linear pharmacokinetics. this selected patient population, adalimumab's long supports every-other-week Coadministration did alter levels