Treatment of ulcerative colitis with an engineered human anti-TNFalpha antibody CDP571

Autor: S. Stephens, L. Clarke, Jonathan M. Rhodes, R. C. Evans, P. Heath, A. I. Morris
Rok vydání: 1997
Předmět:
Zdroj: Alimentary Pharmacology and Therapeutics. 11:1031-1035
ISSN: 1365-2036
0269-2813
Popis: Background: Tumour Necrosis Factor-alpha (TNFα) is a pro-inflammatory cytokine whose expression is increased in the colonic mucosa of patients with active ulcerative colitis. TNFα antibodies have been shown to be beneficial in animal models of bowel inflammation and in Crohn's disease but have not previously been studied in ulcerative colitis. Methods: Patients with mild/moderate ulcerative colitis were treated openly with a single intravenous infusion of 5 mg/kg of an engineered human IgGγ4 antibody CDP571 and monitored for 8 weeks. Results: Fifteen patients entered the study, eight males and seven females, with a mean age of 44 years. Eleven had left-sided disease, four extensive disease and six patients were steroid-unresponsive. The treatment was well tolerated and plasma half-life of CDP571 was ≈7 days. There was a significant reduction from 6.7 to 4.6 (P = 0.023) in the mean Powell–Tuck score by 1 week post-infusion and a reduction to 5.5 was seen at 2 weeks (P = 0.218). Significant but modest reductions also occurred in erythrocyte sedimentation rate and serum C reactive protein in the first 2 weeks. Mean Interleukin-6 plasma concentrations fell from 6.9 to 5.4 pg/mL by week 1, and to 6.1 pg/mL by week 2 (NS). Reductions in sigmoidoscopic score and number of liquid stools were noted but failed to reach statistical significance. Conclusion: A consistent improvement in disease activity was seen in the initial 2 weeks after infusion and the treatment was well tolerated. These promising results support the testing of CDP571 in a larger controlled trial.
Databáze: OpenAIRE
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