The suppressive effect of IRA-378 on adjuvant arthritis was evaluated in Lewis rats and compared with that of auranofin and diclofenac-Na. Drugs were orally administered once daily from Day 0 (adjuvant injection) to Day 16.
(1) IRA-378 (3.1-25.0 mg/kg) dose dependently suppressed the swelling in both adjuvant injected and non injected paws. Auranofin (25.0 and 50.0 mg/kg) suppressed the swelling in the adjuvant injected paw only on Day 1. Diclofenac-Na (0.5 mg/kg) inhibited the swelling only in the injected paw. The degree of suppressive effect of diclofenac-Na on the swelling of the injected paw was similar to that of IRA 378 at a dose of 12.5 mg/kg.
(2) IRA-378 (25.0 mg/kg) significantly suppressed the bone damage in the adjuvant non injected paw by radiographic evaluation on Day 24. Auranofin (50.0 mg/kg) exhibited a tendency to inhibit the bone damage. Diclofenac-Na had no effect on this parameter.
(3) IRA-378 (25.0 mg/kg) significantly improved the thymus atrophy on Day 24. Auranofin and diclofenac-Na did not show any such improvement.
These findings suggest that IRA-378 is a useful drug for the treatment of chronic inflammatory diseases such as rheumatoid arthritis.
