Gastroenterology

Gastroenterology

Volume 137, Issue 4, October 2009, Pages 1250-1260
Gastroenterology

Clinical—Alimentary Tract
Colectomy Rate Comparison After Treatment of Ulcerative Colitis With Placebo or Infliximab

https://doi.org/10.1053/j.gastro.2009.06.061Get rights and content

Background & Aims

The efficacy of infliximab for treating patients with ulcerative colitis has been established.

Methods

The Active Ulcerative Colitis Trial (ACT)-1 and ACT-2 randomized, double-blind, placebo-controlled studies evaluated infliximab induction and maintenance therapy in moderately to severely active ulcerative colitis. Overall, 728 patients received placebo or infliximab (5 or 10 mg/kg) intravenously at weeks 0, 2, and 6, then every 8 weeks through week 46 (ACT-1) or 22 (ACT-2). Colectomy, hospitalization, and surgery/procedure data through 54 weeks after the first infusion were obtained from ACT-1, ACT-2, and associated data sources. In the prespecified analysis, all data were combined to ascertain time to colectomy. Kaplan–Meier product-limit method was used to estimate the cumulative incidence of colectomy, and log-rank test was used to compare the combined infliximab group and placebo.

Results

Eighty-seven percent (630 of 728) of patients had complete colectomy follow-up; 13% (98 of 728) of patients had a median follow-up of 6.2 months. The cumulative incidence of colectomy through 54 weeks was 10% for infliximab and 17% for placebo (P = .02), yielding an absolute risk reduction of 7%. Compared with placebo, fewer ulcerative colitis-related hospitalizations and surgeries/procedures per 100 patient-years of treatment occurred with infliximab therapy: 40 vs 20 (P = .003) and 34 vs 21 (P = .03), respectively. Serious adverse events occurring in infliximab-treated patients included serious infections, tuberculosis, histoplasmosis, listeriosis, and malignancy.

Conclusions

Patients with moderately to severely active ulcerative colitis treated with infliximab were less likely to undergo colectomy through 54 weeks than those receiving placebo.

Section snippets

Patients, Design of the Studies, and Sources of Data

ACT-1 and -2 were randomized, double-blind, placebo-controlled trials conducted at 117 sites between March 2002 and March 2005. Patients were outpatients with moderately to severely active ulcerative colitis defined as a Mayo Clinic score14 of 6 to 12 points and an endoscopic subscore of at least 2 points despite concurrent treatment with corticosteroids and/or azathioprine or 6-mercaptopurine and/or 5-aminosalicylate-containing medications (ACT-2 only). Patients who received intravenous

Patient Disposition and Baseline Characteristics

In the ACT-1 and -2 trials, 728 patients were randomized to treatment: 244 to placebo and 242 each to infliximab 5 and 10 mg/kg. The baseline characteristics were generally similar among treatment groups (Table 1). One hundred forty-two patients from ACT-2 entered the extension trial (31 in the placebo group, and 52 and 59 in the infliximab 5- and 10-mg/kg groups, respectively), 284 patients from ACT-1 and -2 entered RESULTS-UC, and 135 patients with incomplete colectomy data through 54 weeks

Discussion

There has been a paucity of data published on colectomy outcomes in patients with ulcerative colitis who are treated with biologic therapy. Prior to the publication of the ACT trial results, 2 placebo-controlled pilot studies suggested that infliximab might reduce short-term colectomy rates in hospitalized patients with corticosteroid-refractory ulcerative colitis: in 1 study, 3 of 3 patients in the placebo group and 4 of 8 patients in the infliximab group underwent colectomy during short-term

Acknowledgments

The authors thank James Barrett and Mary Whitman, PhD, employees of the Medical Affairs Publications Group, Centocor Ortho Biotech, Inc, for editorial and writing support and Prasheen Agarwal, PhD, an employee of Centocor Research and Development, Inc, for statistical support.

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    This article has an accompanying continuing medical education activity on page 1520. Learning Objective: Upon completion of reading this article, successful learners will be able to apply the results of the study to their practice by weighing the potential benefits and the risk of infliximab in individual patients with moderate to severe ulcerative colitis.

    To view this article's video abstract, go to theAGA's YouTube Channel.

    Conflicts of interest The authors disclose the following: William J. Sandborn, Paul Rutgeerts, Brian G. Feagan, Walter Reinisch, Stephen B. Hanauer, Gary R. Lichtenstein, Willem J. S. de Villiers, Bruce E. Sands, and Jean Frédéric Colombel have served as consultants for and received honoraria and research grants from Centocor Ortho Biotech, Inc. Daniel Present has served as a consultant for and received a research grant from Centocor Research and Development, Inc. Jewel Johanns and Jiandong Lu are employees of Centocor Clinical Research and Development, Inc., a subsidiary of Johnson & Johnson, and own stock in Johnson & Johnson. Allan Olson is a former employee of Centocor Clinical Research and Development, Inc., is currently employed at R. W. Johnson Pharmaceutical Research and Development, and owns stock in Johnson & Johnson. Kevin Horgan is a former employee of Centocor Clinical Research and Development, Inc.

    Funding Supported by a research grant from Centocor Research and Development, Inc, Malvern, Pennsylvania, and Schering Plough, Kenilworth, New Jersey. Supported by a grant (1-UL1-RR024150-01) from the National Center for Research Resources, a component of the National Institutes of Health (NIH) and the NIH Roadmap for Medical Research.

    Some of the results presented in this article were published as an abstract and presented at The American College of Gastroenterology 2007 annual meeting in Philadelphia, Pennsylvania (Am J Gastroenterol 2007;102[Suppl 2]:Abs984); United European Gastroenterology Week 2007 annual meeting in Paris, France (Gut 2007;39:A26); and 2007 CCFA National Research and Clinical Conference, 6th Annual Advances in the Inflammatory Bowel Diseases in Aventura, Florida (Inflamm Bowel Dis 2007;14[Suppl 1]:AbsO-006).

    ClinicalTrials.gov numbers, NCT00036439, NCT00096655, NCT00207688.

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