Miguel Regueiro1, Brian G Feagan2, Bin Zou3, Jewel Johanns3, Marion A Blank4, Marc Chevrier3, Scott Plevy3, John Popp4, Freddy J Cornillie5, Milan Lukas6, Silvio Danese7, Paolo Gionchetti8, Stephen B Hanauer9, Walter Reinisch10, William J Sandborn11, Dario Sorrentino12, Paul Rutgeerts13. 1. Inflammatory Bowel Disease Center and Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: mdr7@pitt.edu. 2. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada. 3. Janssen Research & Development, LLC, Spring House, Pennsylvania. 4. Janssen Scientific Affairs, LLC, Horsham, Pennsylvania. 5. MSD International, Luzern, Switzerland. 6. Charles University, Prague, Czech Republic. 7. Istituto Clinico Humanitas, Milan, Italy. 8. S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 9. Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 10. McMaster University, Hamilton, Ontario, Canada; Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. 11. University of California San Diego, La Jolla, California. 12. Virginia Tech, Carilion School of Medicine, Roanoke, Virginia; Department of Clinical and Experimental Pathology, University of Udine School of Medicine, Udine, Italy. 13. University Hospital Gasthuisberg, Leuven, Belgium.
Abstract
BACKGROUND & AIMS: Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. METHODS: We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012. All study patients had undergone ileocolonic resection within 45 days before randomization. Patients were randomly assigned (1:1) to groups given infliximab (5 mg/kg) or placebo every 8 weeks for 200 weeks. The primary end point was clinical recurrence, defined as a composite outcome consisting of a CD Activity Index score >200 and a ≥70-point increase from baseline, and endoscopic recurrence (Rutgeerts score ≥i2, determined by a central reader) or development of a new or re-draining fistula or abscess, before or at week 76. Endoscopic recurrence was a major secondary end point. RESULTS: A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group, but this difference was not statistically significant (12.9% vs 20.0%; absolute risk reduction [ARR] with infliximab, 7.1%; 95% confidence interval: -1.3% to 15.5%; P = .097). A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group (30.6% vs 60.0%; ARR with infliximab, 29.4%; 95% confidence interval: 18.6% to 40.2%; P < .001). Additionally, a significantly smaller proportion of patients in the infliximab group had endoscopic recurrence based only on Rutgeerts scores ≥i2 (22.4% vs 51.3%; ARR with infliximab, 28.9%; 95% confidence interval: 18.4% to 39.4%; P < .001). Patients previously treated with anti-tumor necrosis factor agents or those with more than 1 resection were at greater risk for clinical recurrence. The safety profile of infliximab was similar to that from previous reports. CONCLUSIONS:Infliximab is not superior to placebo in preventing clinical recurrence after CD-related resection. However, infliximab does reduce endoscopic recurrence. ClinicalTrials.gov ID NCT01190839.
RCT Entities:
BACKGROUND & AIMS: Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. METHODS: We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012. All study patients had undergone ileocolonic resection within 45 days before randomization. Patients were randomly assigned (1:1) to groups given infliximab (5 mg/kg) or placebo every 8 weeks for 200 weeks. The primary end point was clinical recurrence, defined as a composite outcome consisting of a CD Activity Index score >200 and a ≥70-point increase from baseline, and endoscopic recurrence (Rutgeerts score ≥i2, determined by a central reader) or development of a new or re-draining fistula or abscess, before or at week 76. Endoscopic recurrence was a major secondary end point. RESULTS: A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group, but this difference was not statistically significant (12.9% vs 20.0%; absolute risk reduction [ARR] with infliximab, 7.1%; 95% confidence interval: -1.3% to 15.5%; P = .097). A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group (30.6% vs 60.0%; ARR with infliximab, 29.4%; 95% confidence interval: 18.6% to 40.2%; P < .001). Additionally, a significantly smaller proportion of patients in the infliximab group had endoscopic recurrence based only on Rutgeerts scores ≥i2 (22.4% vs 51.3%; ARR with infliximab, 28.9%; 95% confidence interval: 18.4% to 39.4%; P < .001). Patients previously treated with anti-tumornecrosis factor agents or those with more than 1 resection were at greater risk for clinical recurrence. The safety profile of infliximab was similar to that from previous reports. CONCLUSIONS:Infliximab is not superior to placebo in preventing clinical recurrence after CD-related resection. However, infliximab does reduce endoscopic recurrence. ClinicalTrials.gov ID NCT01190839.
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