Early Mucosal Healing With Infliximab Is Associated With Improved Long-term Clinical Outcomes in Ulcerative Colitis
Background & Aims
In the Active Ulcerative Colitis Trial (ACT)-1 and ACT-2, patients with ulcerative colitis treated with infliximab were more likely than those given placebo to have a clinical response, undergo remission, and have mucosal healing. We investigated the association between early improvement (based on endoscopy) and subsequent clinical outcome.
Methods
Patients underwent endoscopic evaluations at weeks 0, 8, 30, and 54 (ACT-1 only), and were categorized into 4 subgroups by week 8 (Mayo endoscopy subscore, 0–3). The association of week 8 endoscopy subscores, subsequent colectomy risk, symptoms and corticosteroid use outcomes were analyzed. Mucosal healing was defined as a Mayo endoscopy subscore of 0 (normal) or 1 (mild).
Results
Infliximab-treated patients with lower week 8 endoscopy subscores were less likely to progress to colectomy through 54 weeks of follow-up evaluation (P = .0004). This trend was not observed among patients given placebo (P = .47). Patients with lower endoscopy subscores achieved better symptomatic and corticosteroid use outcomes at weeks 30 and 54 (P < .0001, infliximab; P < .01, placebo). Among patients who achieved clinical response at week 8, trends in subsequent clinical outcomes by week 8 endoscopy subscores were generally consistent with that for the overall patient population; no trends were observed among patients who achieved clinical remission.
Conclusions
The degree of mucosal healing after 8 weeks of infliximab was correlated with improved clinical outcomes including colectomy. Similar trends were observed for all outcomes except colectomy among the subgroup with clinical response at week 8. The degree of mucosal healing at week 8 among those in clinical remission did not predict subsequent disease course.
Keywords: Endoscopic Improvement, Mucosal Healing, Colectomy, Symptomatic Outcomes
Abbreviations used in this paper: 5-ASA, 5-aminosalycilates, ACT, Active Ulcerative Colitis Trial, RESULTS-UC, Remicade Safety Under Long-term Study in Ulcerative Colitis
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Conflicts of interest Paul Rutgeerts, William Sandborn, Jean Frédéric Colombel, Stephen Hanauer, Gary Lichtenstein, Walter Reinisch, Bruce Sands, and Brian Feagan have served as consultants for Centocor Research & Development, a division of Johnson & Johnson Pharmaceutical Research & Development, LLC and Schering–Plough, a subsidiary of Merck & Co, Inc; Paul Rutgeerts, William Sandborn, Stephen Hanauer, Bruce Sands, Brian Feagan, Walter Reinisch, and Gary Lichtenstein have participated in continuing medical education events supported by unrestricted educational grants from Centocor Research & Development, a division of Johnson & Johnson Pharmaceutical Research & Development, LLC and Schering Corporation, a subsidiary of Merck & Co, Inc; Björn Oddens and Yanxin Wang are employees of Schering Corporation, a subsidiary of Merck & Co, Inc; Colleen Marano and Richard Strauss are employees of the Department of Immunology, Centocor Research & Development, a division of Johnson & Johnson Pharmaceutical Research & Development, LLC, and Yinghua Lang is an employee of the Department of Biostatistics, Centocor Research & Development, a division of Johnson & Johnson Pharmaceutical Research & Development, LLC; and Dirk Esser is a former employee of Janssen Biologics BV and is currently an employee of Boerhringer–Ingelheim.
Funding Supported by a research grant from Centocor Research & Development, a division of Johnson & Johnson Pharmaceutical Research & Development, LLC (Malvern, PA) and Schering Corporation, a subsidiary of Merck & Co, Inc (Kenilworth, NJ); this study was designed and conducted by the ACT-1 and ACT-2 Steering Committees, Centocor Research & Development, a division of Johnson & Johnson Pharmaceutical Research & Development, LLC and Schering Corporation (a subsidiary of Merck & Co, Inc) who jointly analyzed and interpreted the data, and contributed to the manuscript; Drs Colombel, Rutgeerts, and Sandborn prepared the first draft of the manuscript, and the ACT-1 and ACT-2 Steering Committee made the decision to publish; editorial and writing support was provided by James P. Barrett, an employee of the Medical Affairs Publications Group, Janssen Services, LLC.
PII: S0016-5085(11)00904-8
doi:10.1053/j.gastro.2011.06.054
© 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
