Gastroenterology

Gastroenterology

Volume 120, Issue 6, May 2001, Pages 1330-1338
Gastroenterology

Alimentary Tract
An engineered human antibody to TNF (CDP571) for active Crohn's disease: A randomized double-blind placebo-controlled trial,☆☆,

https://doi.org/10.1053/gast.2001.24042Get rights and content

Abstract

Background & Aims: We evaluated CDP571, a humanized antibody to tumor necrosis factor, for the treatment of active Crohn's disease. Methods: One hundred sixty-nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week placebo-controlled trial. Patients were initially randomized to a single dose of 10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess subsequent dosing intervals. The primary endpoint was clinical response at week 2, defined as a decrease in the Crohn's Disease Activity Index score ≥ 70 points. Results: At week 2, clinical response occurred in 45% of CDP571-treated patients compared with 27% of patients in the placebo group (P = 0.023). Patients appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of the results for secondary endpoints were statistically significant. The frequency of severe or serious adverse events was similar among all groups. Conclusions: CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment of patients with moderate-to-severe Crohn's disease. Preliminary evidence suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks may also be beneficial, but additional studies are needed.

GASTROENTEROLOGY 2001;120:1330-1338

Section snippets

Selection of patients

The study was performed between June 1998 and June 1999. Eligible patients were at least 18 years of age and had moderately to severely active Crohn's disease, as defined by a score of 220–450 on the Crohn's Disease Activity Index (CDAI).12

Eligible patients had Crohn's disease confirmed by radiologic, endoscopic, or histologic criteria. The following patients were not eligible: those with an ileostomy or colostomy; those with a serious intercurrent infection or other clinically important active

Results

A total of 193 patients were screened and randomized. Of those, 169 patients received the IV study medication and are included in the safety analysis. Fifty-eight received placebo initially and as maintenance 8 weekly (n = 27) or 12 weekly (n = 31); 54 received 10 mg/kg CDP571 initially and as maintenance 8 weekly (n = 29) or 12 weekly (n = 25); and 57 received 20 mg/kg CDP571 initially and then 10 mg/kg as maintenance 8 weekly (n = 28) or 12 weekly (n = 29). Two patients in the 12 weekly

Discussion

We found CDP571 to be effective for inducing a clinical response at 2 weeks in patients with mildly to severely active Crohn's disease, using a decrease in baseline CDAI score of either ≥ 70 points or ≥ 100 points as the definition or response. In further support of these results, trends toward efficacy for CDP571 at 2 weeks as measured by the rate of clinical remission (CDAI score < 150), decrease in CDAI score from baseline, and increased quality of life were also observed. Although the study

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Address requests for reprints to: William J. Sandborn, M.D., Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55905. e-mail: [email protected]; fax: (507) 266-0335.

☆☆

William Sandborn, Brian Feagan, Stephen Hanauer, Daniel Present, Lloyd Sutherland, Michael Kamm, Christopher Hawkey, and Stephan Targan have all served as consultants for Celltech Therapeutics Ltd. Claire Novak and Patricia Heath are employees of Celltech and hold its stock.

CDP571 Crohn's Disease Study Group investigators include the following: Simmy Bank, M.D, Long Island Jewish Medical Center, New Hyde Park, NY; Fabio Cominelli, M.D., University of Virginia, Charlottesville, VA; Charles Elson, M.D., C. Mel Wilcox, M.D., University of Alabama, Birmingham, AL; Stephen Hanauer, M.D., University of Chicago, Chicago, IL; Gary Lichtenstein, M.D., Julius Deren, M.D., University of Pennsylvania, Philadelphia, PA; Daniel Present, M.D., L. Meyer, M.D., S. Meyer, M.D., D. Sachar, M.D., Mount Sinai School of Medicine, New York, NY; William J. Sandborn, M.D., William Tremaine, M.D., Mayo Clinic, Rochester, MN; Stephan Targan, M.D., Lori Kam, M.D., Eric Vasiliauskas, M.D., Cedars Sinai Medical Center, Los Angeles, CA; Douglas Wolf, M.D., Bruce Salzberg, M.D., Atlanta Gastroenterology Associates, Atlanta, GA; Andre Archambault, M.D., University of Montreal, Montreal, QE, Canada; Jeffrey Baker, M.D., Rima Petroniene, M.D., St Michael's Hospital, University of Toronto, Toronto, ON, Canada; Charles Bernstein, M.D., University of Manitoba, Winnipeg, Manitoba, Canada; Laurington Da Costa, M.D., Hotel Dieu Hospital, Kingston, ON, Canada; Chrystian Dallaire, M.D., Laval University, Quebec, QE, Canada; Brian Feagan, M.D., Jaime Gregor, M.D., University of Western Ontario, London, ON, Canada; Lloyd Sutherland, M.D., University of Calgary, Calgary, AB, Canada; Douglas Chalmers, M.D., Leeds General Infirmary, Leeds, England; Christopher Hawkey, M.D., William Stacks, M.D., University Hospital, Nottingham, England; Humphrey Hodgeson, M.D., Julian Walters, M.D., Royal Free Hospital, London, England; Michael Kamm, M.D., Sally Bell, M.D., St. Mark's Hospital, London, England; Jonathan Rhodes, M.D., University of Liverpool, Liverpool, England; Patricia K. Heath, M.D., Claire Novak, M.Sc., Celltech Therapeutics Ltd., Slough, England.

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