Alimentary TractAn engineered human antibody to TNF (CDP571) for active Crohn's disease: A randomized double-blind placebo-controlled trial☆,☆☆,★
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
References (15)
- et al.
Tumour necrosis factor alpha in stool as a marker of intestinal inflammation [see comments]
Lancet
(1992) - et al.
Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease
Gastroenterology
(1999) - et al.
Humanized antibodies
Immunol Today
(1993) - et al.
Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease [see comments]
Lancet
(1997) - et al.
Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study
Gastroenterology
(1976) - et al.
Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial Study Group
Gastroenterology
(1994) - et al.
A randomized, double-blind, placebo-controlled, multi-center trial of the engineered human antibody to TNF (CDP571) for steroid sparing and maintenance of remission in patients with steroid-dependent Crohn's disease (abstr)
Gastroenterology
(2000)
Cited by (272)
Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials of Crohn's Disease: A Systematic Review
2018, Clinical Gastroenterology and HepatologyCitation Excerpt :Fistula response and remission to therapy were defined in 6 induction and 4 maintenance RCTs. Most commonly, response was defined by closure of >50% of draining fistulae, and remission was defined by closure of all draining fistulae, maintained for at least 2 study visits.37,38,44,49,54,79,109,113,114,116 Twenty-one induction (25.9%), 6 maintenance (13.6%), and 5 postoperative prevention (71.4%) trials reported endoscopic outcomes, primarily in the last 2 decades (Figure 2).
Patient-reported outcomes as primary end points in clinical trials of inflammatory bowel disease
2014, Clinical Gastroenterology and HepatologySLE criteria are by necessity still based on clinical (and immunological) criteria items
2024, Expert Review of Clinical ImmunologyClinical remission in paired phase two and three studies in inflammatory bowel disease: A systematic review with meta-analysis
2023, European Journal of Gastroenterology and HepatologyMedical treatment of perianal crohn disease
2023, Pediatric Inflammatory Bowel Disease
- ☆
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.