Abstract
Anti-tumor necrosis factor-α (TNFα) antibody in combination with methotrexate dramatically decreases joint destruction in rheumatoid arthritis. The aim of this study was to examine combined treatment with N-[1-(4-{[4-(pyrimidin-2-yl)piperazin-1-yl]methyl}phenyl)cyclopropyl] acetamide HCl (Y-40138) and methotrexate in rat adjuvant-induced arthritis. The increase in hindpaw volume and joint destruction was suppressed by single therapeutic administration (days 15–20) of Y-40138 (30 mg/kg, p.o.), but not by prophylactic administration (days 1–9). However, arthritic progression was suppressed by single prophylactic administration of methotrexate (0.3 mg/kg, p.o.), but not by therapeutic administration. Combined administration (days 10–20) of Y-40138 (0.3–1 mg/kg) and methotrexate (0.03 mg/kg) synergistically suppressed the increase in hindpaw volume and joint destruction. We concluded that Y-40138 in combination with methotrexate synergistically suppressed arthritic progression. These data suggest that combined treatment with Y-40138 and methotrexate may increase efficacy of therapy for rheumatoid arthritis.
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