TREATMENT OF ULCERATIVE-COLITIS WITH AN ENGINEERED HUMAN ANTI-TNF-ALPHA ANTIBODY CDP571

Background: Tumour Necrosis Factor-alpha (TNF alpha) is a pro-inflamma tory cytokine whose expression is increased in the colonic mucosa of p atients with active ulcerative colitis. TNF alpha 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 col itis. Methods: Patients with mild/moderate ulcerative colitis were tre ated openly with a single intravenous infusion of 5 mg/kg of an engine ered human IgG gamma 4 antibody CDP571 and monitored for 8 weeks. Resu lts: Fifteen patients entered the study, eight males and seven females , with a mean age of 44 years. Eleven had left-sided disease, four ext ensive disease and six patients were steroid-unresponsive. The treatme nt was well tolerated and plasma half-life of CDP571 was approximate t o 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 reductio n to 5.5 was seen at 2 weeks (P = 0.218). Significant but modest reduc tions also occurred in erythrocyte sedimentation rate and serum C reac tive protein in the first 2 weeks. Mean Interleukin-6 plasma concentra tions 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 promi sing results support the testing of CDP571 in a larger controlled tria l.