bn-50730 and Arthritis--Rheumatoid

To evaluate the efficacy and tolerance of a platelet activating factor-acether (PAF) antagonist, BN 50730, in patients with rheumatoid arthritis (RA).. A total of 56 patients with active RA were enrolled in a multicenter, double blind, placebo controlled study of BN 50730. Patients received either BN 50730 (40 mg orally bid) or placebo for 84 days.. Treatment with BN 50730 resulted in no improvement and was no more effective than placebo in improving clinical and biological indices of RA activity. Adverse events were observed in the 2 treatment groups, and BN 50730 was generally well tolerated.. PAF antagonist BN 50730 at a daily dose of 80 mg was ineffective in the treatment of RA.

Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Azepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Platelet Activating Factor; Platelet Aggregation Inhibitors; Thienopyridines; Treatment Outcome; Triazoles

To determine the efficacy and safety of a platelet activating factor (PAF) antagonist, BN 50730, in patients with rheumatoid arthritis.. Ten patients with an active disease were treated for 4 weeks with a PAF receptor antagonist, BN 50730, given orally (40 mg twice daily). The treatment period was followed by a 4 weeks followup period.. Clinical indicators of disease activity significantly improved during the treatment period, with a progressive return to baseline values during the followup period. No significant change in laboratory variables was observed. The tolerance of the treatment was excellent, and no clinical or laboratory evidence of side effects was recorded.. These results need to be confirmed in a controlled study, but suggest an antiinflammatory effect. PAF antagonists could represent a new class of therapeutic agents in inflammatory arthropathies.

Topics: Adult; Aged; Arthritis, Rheumatoid; Azepines; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Severity of Illness Index; Thienopyridines; Treatment Outcome; Triazoles

To examine the effect of treatment with the platelet activating factor (PAF) receptor antagonist BN 50730 on the clinical and morphological evolution of collagen induced arthritis in mice.. Mice with collagen induced arthritis were treated with BN 50730 (0.3, 1, 3 mg/kg) or vehicle (0.1% Tween-20 in saline) once a day, from 3 days before the induction of the arthritis to 70 days after. Disease evolution was followed daily by inspection of inflammatory signs and measurement of the knee joint diameter on Days 0, 40, and 70. At the end of the treatment period, the morphological evaluation of the synovial membrane, the immunodetection of fibronectin, and the content of cartilage proteoglycans were studied.. On Day 40, mice receiving the highest dose of BN 50730 (3 mg/kg) showed a reduction in the knee joint diameter in comparison with untreated (2.1 +/- 0.2 vs 2.8 +/- 0.4 mm, p < 0.01). On Day 70, animals receiving 1 and 3 mg/kg had a normal knee diameter, while it remained enlarged in the untreated ones. In BN 50730 treated mice (3 mg/kg) we also observed a significant reduction of the inflammation score (0.1 +/- 0.1 vs 2.5 +/- 0.2 in the untreated) and deposition of fibronectin. Depletion of cartilage proteoglycans was also reversed with BN 50730.. The beneficial effects in this model of joint injury after administration of the PAF antagonist BN 50730 suggest that PAF could be implicated in the pathogenesis of chronic arthritis.

Topics: Animals; Arthritis, Rheumatoid; Azepines; Collagen; Disease Models, Animal; Female; Fibronectins; Immunohistochemistry; Joints; Mice; Mice, Inbred DBA; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Thienopyridines; Triazoles