Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease after Ileocolonic Resection

Miguel Regueiro; Brian G. Feagan; Bin Zou; Jewel Johanns; Marion A. Blank; Marc Chevrier; Scott Plevy; John Popp; Freddy J. Cornillie; Milan Lukas; Silvio Danese; Paolo Gionchetti; Stephen B. Hanauer; Walter Reinisch; William J. Sandborn; Dario Sorrentino; Paul Rutgeerts; H. Debinski; T. Florin; D. Hetzel; I. Lawrance; G. Radford-Smith; A. Sloss; S. Gassner; T. Haas; G. Reicht; M. Strasser; H. Vogelsang; P. Bossuyt; O. Dewit; G. D'Haens; D. Franchimont; E. Louis; S. Vermeire; C. N. Bernstein; R. Bourdages; N. Chiba; S. S. Dhalla; R. N. Fedorak; J. R. Lachance; R. Panaccione; M. Ropeleski; B. Singh Salh; J. F. Colombel; M. Allez; P. Desreumaux; J. L. Dupas; J. C. Grimaud; X. Hebuterne; D. Laharie; E. Lerebours; L. Peyrin-Biroulet; J. M. Reimund; S. Viennot; F. Zerbib; C. Antoni; R. Atreya; D. C. Baumgart; C. Berg; U. Boecker; G. Bramkamp; C. Bünning; R. Ehehalt; S. Howaldt; T. Kucharzik; H. G. Lamprecht; J. Mudter; J. C. Preiss; S. Schreiber; U. Seidler; I. Altorjay; J. Banai; P. L. Lakatos; M. Varga; A. Vincze; I. Avni-Biron; S. Fishman; G. M. Fraser; E. Goldin; D. Rachmilewitz; V. Annese; S. Ardizzone; L. Biancone; F. Bossa; W. Fries; G. Maconi; G. Terrosu; P. Usai; G. R. D'Haens; R. B. Gearry; J. Hill; D. S. Rowbotham; M. Schultz; R. S. Stubbs; D. Wallace; R. S. Walmsley; J. Wyeth; E. Malecka-Panas; L. Paradowski; J. Regula; I. P. Beales; S. Campbell; A. B. Hawthorne; M. Parkes; S. P. Travis; J. P. Achkar; B. W. Behm; S. J. Bickston; K. J. Brown; M. V. Chiorean; W. J.S. Devilliers; D. E. Elliott; D. Grunkmeier; J. W. Hamilton; J. S. Hanson; R. Hardi; D. J. Helper; H. Herfarth; P. D.R. Higgins; W. H. Holderman; R. Kottoor; M. D. Kreines; B. I. Leman; X. Li; E. V. Loftus; M. Noar; I. Oikonomou; J. Onken; K. A. Peterson; R. P. Phillips; C. W. Randall; M. Ricci; T. Ritter; D. T. Rubin; M. Safdi; L. Sauberman; E. Scherl; R. P. Schwarz; S. Sedghi; I. Shafran; C. A. Sninsky; I. Stein; J. Swoger; J. Vecchio; D. I. Weinberg; L. D. Wruble; V. Yajnik; Z. Younes

doi:10.1053/j.gastro.2016.02.072

Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease after Ileocolonic Resection

Miguel Regueiro, Brian G. Feagan, Bin Zou, Jewel Johanns, Marion A. Blank, Marc Chevrier, Scott Plevy, John Popp, Freddy J. Cornillie, Milan Lukas, Silvio Danese, Paolo Gionchetti, Stephen B. Hanauer, Walter Reinisch, William J. Sandborn, Dario Sorrentino, Paul Rutgeerts, H. Debinski, T. Florin, D. HetzelI. Lawrance, G. Radford-Smith, A. Sloss, S. Gassner, T. Haas, G. Reicht, M. Strasser, H. Vogelsang, P. Bossuyt, O. Dewit, G. D'Haens, D. Franchimont, E. Louis, S. Vermeire, C. N. Bernstein, R. Bourdages, N. Chiba, S. S. Dhalla, R. N. Fedorak, J. R. Lachance, R. Panaccione, M. Ropeleski, B. Singh Salh, J. F. Colombel, M. Allez, P. Desreumaux, J. L. Dupas, J. C. Grimaud, X. Hebuterne, D. Laharie, E. Lerebours, L. Peyrin-Biroulet, J. M. Reimund, S. Viennot, F. Zerbib, C. Antoni, R. Atreya, D. C. Baumgart, C. Berg, U. Boecker, G. Bramkamp, C. Bünning, R. Ehehalt, S. Howaldt, T. Kucharzik, H. G. Lamprecht, J. Mudter, J. C. Preiss, S. Schreiber, U. Seidler, I. Altorjay, J. Banai, P. L. Lakatos, M. Varga, A. Vincze, I. Avni-Biron, S. Fishman, G. M. Fraser, E. Goldin, D. Rachmilewitz, V. Annese, S. Ardizzone, L. Biancone, F. Bossa, W. Fries, G. Maconi, G. Terrosu, P. Usai, G. R. D'Haens, R. B. Gearry, J. Hill, D. S. Rowbotham, M. Schultz, R. S. Stubbs, D. Wallace, R. S. Walmsley, J. Wyeth, E. Malecka-Panas, L. Paradowski, J. Regula, I. P. Beales, S. Campbell, A. B. Hawthorne, M. Parkes, S. P. Travis, J. P. Achkar, B. W. Behm, S. J. Bickston, K. J. Brown, M. V. Chiorean, W. J.S. Devilliers, D. E. Elliott, D. Grunkmeier, J. W. Hamilton, J. S. Hanson, R. Hardi, D. J. Helper, H. Herfarth, P. D.R. Higgins, W. H. Holderman, R. Kottoor, M. D. Kreines, B. I. Leman, X. Li, E. V. Loftus, M. Noar, I. Oikonomou, J. Onken, K. A. Peterson, R. P. Phillips, C. W. Randall, M. Ricci, T. Ritter, D. T. Rubin, M. Safdi, L. Sauberman, E. Scherl, R. P. Schwarz, S. Sedghi, I. Shafran, C. A. Sninsky, I. Stein, J. Swoger, J. Vecchio, D. I. Weinberg, L. D. Wruble, V. Yajnik, Z. Younes

Gastroenterology and Hepatology

Research output: Contribution to journal › Article › peer-review

126 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1568-1578
Number of pages	11
Journal	Gastroenterology
Volume	150
Issue number	7
DOIs	https://doi.org/10.1053/j.gastro.2016.02.072
State	Published - Jun 1 2016

Keywords

Anti-TNF
CDAI
Inflammatory Bowel Disease
PREVENT

ASJC Scopus subject areas

Hepatology
Gastroenterology

Access to Document

10.1053/j.gastro.2016.02.072

Cite this

Regueiro, M., Feagan, B. G., Zou, B., Johanns, J., Blank, M. A., Chevrier, M., Plevy, S., Popp, J., Cornillie, F. J., Lukas, M., Danese, S., Gionchetti, P., Hanauer, S. B., Reinisch, W., Sandborn, W. J., Sorrentino, D., Rutgeerts, P., Debinski, H., Florin, T., ... Younes, Z. (2016). Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease after Ileocolonic Resection. Gastroenterology, 150(7), 1568-1578. https://doi.org/10.1053/j.gastro.2016.02.072

Regueiro, M, Feagan, BG, Zou, B, Johanns, J, Blank, MA, Chevrier, M, Plevy, S, Popp, J, Cornillie, FJ, Lukas, M, Danese, S, Gionchetti, P, Hanauer, SB, Reinisch, W, Sandborn, WJ, Sorrentino, D, Rutgeerts, P, Debinski, H, Florin, T, Hetzel, D, Lawrance, I, Radford-Smith, G, Sloss, A, Gassner, S, Haas, T, Reicht, G, Strasser, M, Vogelsang, H, Bossuyt, P, Dewit, O, D'Haens, G, Franchimont, D, Louis, E, Vermeire, S, Bernstein, CN, Bourdages, R, Chiba, N, Dhalla, SS, Fedorak, RN, Lachance, JR, Panaccione, R, Ropeleski, M, Singh Salh, B, Colombel, JF, Allez, M, Desreumaux, P, Dupas, JL, Grimaud, JC, Hebuterne, X, Laharie, D, Lerebours, E, Peyrin-Biroulet, L, Reimund, JM, Viennot, S, Zerbib, F, Antoni, C, Atreya, R, Baumgart, DC, Berg, C, Boecker, U, Bramkamp, G, Bünning, C, Ehehalt, R, Howaldt, S, Kucharzik, T, Lamprecht, HG, Mudter, J, Preiss, JC, Schreiber, S, Seidler, U, Altorjay, I, Banai, J, Lakatos, PL, Varga, M, Vincze, A, Avni-Biron, I, Fishman, S, Fraser, GM, Goldin, E, Rachmilewitz, D, Annese, V, Ardizzone, S, Biancone, L, Bossa, F, Fries, W, Maconi, G, Terrosu, G, Usai, P, D'Haens, GR, Gearry, RB, Hill, J, Rowbotham, DS, Schultz, M, Stubbs, RS, Wallace, D, Walmsley, RS, Wyeth, J, Malecka-Panas, E, Paradowski, L, Regula, J, Beales, IP, Campbell, S, Hawthorne, AB, Parkes, M, Travis, SP, Achkar, JP, Behm, BW, Bickston, SJ, Brown, KJ, Chiorean, MV, Devilliers, WJS, Elliott, DE, Grunkmeier, D, Hamilton, JW, Hanson, JS, Hardi, R, Helper, DJ, Herfarth, H, Higgins, PDR, Holderman, WH, Kottoor, R, Kreines, MD, Leman, BI, Li, X, Loftus, EV, Noar, M, Oikonomou, I, Onken, J, Peterson, KA, Phillips, RP, Randall, CW, Ricci, M, Ritter, T, Rubin, DT, Safdi, M, Sauberman, L, Scherl, E, Schwarz, RP, Sedghi, S, Shafran, I, Sninsky, CA, Stein, I, Swoger, J, Vecchio, J, Weinberg, DI, Wruble, LD, Yajnik, V & Younes, Z 2016, 'Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease after Ileocolonic Resection', Gastroenterology, vol. 150, no. 7, pp. 1568-1578. https://doi.org/10.1053/j.gastro.2016.02.072

@article{586b7e86e5e8421eb476c0f356fd6a8d,

title = "Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease after Ileocolonic Resection",

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.",

keywords = "Anti-TNF, CDAI, Inflammatory Bowel Disease, PREVENT",

author = "Miguel Regueiro and Feagan, {Brian G.} and Bin Zou and Jewel Johanns and Blank, {Marion A.} and Marc Chevrier and Scott Plevy and John Popp and Cornillie, {Freddy J.} and Milan Lukas and Silvio Danese and Paolo Gionchetti and Hanauer, {Stephen B.} and Walter Reinisch and Sandborn, {William J.} and Dario Sorrentino and Paul Rutgeerts and H. Debinski and T. Florin and D. Hetzel and I. Lawrance and G. Radford-Smith and A. Sloss and S. Gassner and T. Haas and G. Reicht and M. Strasser and H. Vogelsang and P. Bossuyt and O. Dewit and G. D'Haens and D. Franchimont and E. Louis and S. Vermeire and Bernstein, {C. N.} and R. Bourdages and N. Chiba and Dhalla, {S. S.} and Fedorak, {R. N.} and Lachance, {J. R.} and R. Panaccione and M. Ropeleski and {Singh Salh}, B. and Colombel, {J. F.} and M. Allez and P. Desreumaux and Dupas, {J. L.} and Grimaud, {J. C.} and X. Hebuterne and D. Laharie and E. Lerebours and L. Peyrin-Biroulet and Reimund, {J. M.} and S. Viennot and F. Zerbib and C. Antoni and R. Atreya and Baumgart, {D. C.} and C. Berg and U. Boecker and G. Bramkamp and C. B{\"u}nning and R. Ehehalt and S. Howaldt and T. Kucharzik and Lamprecht, {H. G.} and J. Mudter and Preiss, {J. C.} and S. Schreiber and U. Seidler and I. Altorjay and J. Banai and Lakatos, {P. L.} and M. Varga and A. Vincze and I. Avni-Biron and S. Fishman and Fraser, {G. M.} and E. Goldin and D. Rachmilewitz and V. Annese and S. Ardizzone and L. Biancone and F. Bossa and W. Fries and G. Maconi and G. Terrosu and P. Usai and D'Haens, {G. R.} and Gearry, {R. B.} and J. Hill and Rowbotham, {D. S.} and M. Schultz and Stubbs, {R. S.} and D. Wallace and Walmsley, {R. S.} and J. Wyeth and E. Malecka-Panas and L. Paradowski and J. Regula and Beales, {I. P.} and S. Campbell and Hawthorne, {A. B.} and M. Parkes and Travis, {S. P.} and Achkar, {J. P.} and Behm, {B. W.} and Bickston, {S. J.} and Brown, {K. J.} and Chiorean, {M. V.} and Devilliers, {W. J.S.} and Elliott, {D. E.} and D. Grunkmeier and Hamilton, {J. W.} and Hanson, {J. S.} and R. Hardi and Helper, {D. J.} and H. Herfarth and Higgins, {P. D.R.} and Holderman, {W. H.} and R. Kottoor and Kreines, {M. D.} and Leman, {B. I.} and X. Li and Loftus, {E. V.} and M. Noar and I. Oikonomou and J. Onken and Peterson, {K. A.} and Phillips, {R. P.} and Randall, {C. W.} and M. Ricci and T. Ritter and Rubin, {D. T.} and M. Safdi and L. Sauberman and E. Scherl and Schwarz, {R. P.} and S. Sedghi and I. Shafran and Sninsky, {C. A.} and I. Stein and J. Swoger and J. Vecchio and Weinberg, {D. I.} and Wruble, {L. D.} and V. Yajnik and Z. Younes",

note = "Funding Information: Conflicts of interest The authors disclose the following: Miguel Regueiro has received consulting fees from AbbVie, Janssen Biotech, Inc., Takeda, and UCB Pharma; served as a Scientific Advisory Board member for AbbVie, Janssen Biotech, Takeda, and UCB Pharma; and received research grants from AbbVie, Janssen Biotech, Takeda, and UCB Pharma. Brian G. Feagan has received consulting fees from Abbott/AbbVie, Actogenix, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Axcan, Baxter Healthcare Corp., Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech, LLC. (formerly Centocor, Inc.), Janssen Research & Development, LLC., Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Merck, Millennium, Nektar, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, Tillotts, UCB Pharma, Vertex Pharma, Warner-Chilcott, Wyeth, Zealand, Zyngenia; payments for lectures/speakers bureau from Abbott/AbbVie, Janssen Research & Development, LLC., Takeda, Warner-Chilcott and UCB Pharma; and served as a Scientific Advisory Board member for Avaxia Biologics Inc., Bristol-Myers Squibb, Celgene, Janssen Biotech, LLC. (formerly Centocor, Inc.), Elan/Biogen, Ferring, Janssen Research & Development, LLC., Merck, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, Tillotts Pharma AG and UCB Pharma Marion A. Blank and John Popp are employees of Janssen Scientific Affairs, LLC. Bin Zou and Scott Plevy are employees of Janssen Research & Development, LLC. Freddy J. Cornillie is currently an employee of MSD International and was an employee of Janssen Biologics BV, Leiden, The Netherlands during the study conduct. Silvio Danese has received consulting fees from AbbVie, Astra Zeneca, MSD, Takeda Millennium, Salix Pharmaceuticals, and Pfizer. Paolo Gionchetti has received consulting fees from AbbVie, MSD, and Takeda; and has received payments for speakers{\textquoteright} bureau from Ferring and Chiesi. Stephen B. Hanauer has received consulting fees from Janssen Research & Development, LLC., payments for speakers bureau participation from Janssen Research & Development, LLC., and served as a Scientific Advisory Board member for Janssen Research & Development, LLC. Walter Reinisch has served as a speaker, consultant, and/or advisory board member for Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Janssen Biotech, LLC. (formerly Centocor, Inc.), Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gr{\"u}nenthal, Janssen Research & Development, LLC., Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zygenia, and 4SC. William J. Sandborn has received consulting fees from Abbott, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corp, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys Inc, Atlantic Healthcare Ltd, Aptalis, BioBalance Corp, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, EnGene Inc, Eli Lilly, Enteromedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexio Therapeutics Inc, Funxional Therapeutics Ltd, Genzyme Corp, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, Janssen Research & Development, LLC., KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera Corp, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millenium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Ltd, Purgenesis Technologies Inc, Relypsa Inc, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering Plough, Shire Pharmaceuticals, Sigmoid Pharma Ltd, Sirtris Pharmaceuticals, SLA Pharma UK Ltd, Targacept, Teva Pharmaceuticals, Therakos, Tilliotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Ltd, Warner Chilcott UK Ltd, and Wyeth; research grants from Abbott, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen Research & Development, LLC., Milennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals, and UCB Pharma; payments for lectures/speakers bureau from Abbott, Bristol-Myers Squibb, and Janssen Research & Development, LLC; and holds stock/stock options in Enteromedics. Dario Sorrentino has received consulting fees from Abbott/AbbVie, Schering-Plough, MSD, Janssen Research & Development, LLC., Centocor Inc., TechLab, Hoffmann-LaRoche, Giuliani, Schering-Plough, and Ferring; research grants from AbbVie, Janssen Research & Development, LLC, Schering-Plough, TechLab, Centocor and serves in the Speakers Bureau of AbbVie. Paul Rutgeerts has received research funding, and/or served as speaker, consultant and/or advisory board member for Abbott Laboratories, Janssen Research & Development, LLC., Merck Research Laboratories, Merck Serono, UCB Pharma, Millenium/Takeda, Genentech/Hoffman LaRoche, Neovacs, Bristol Myers Squibb, Robarts, Tillotts, Pfizer, and Falk Pharma. The remaining author discloses no conflicts. Publisher Copyright: {\textcopyright} 2016 AGA Institute.",

year = "2016",

month = jun,

day = "1",

doi = "10.1053/j.gastro.2016.02.072",

language = "English (US)",

volume = "150",

pages = "1568--1578",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

number = "7",

}

TY - JOUR

T1 - Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease after Ileocolonic Resection

AU - Regueiro, Miguel

AU - Feagan, Brian G.

AU - Zou, Bin

AU - Johanns, Jewel

AU - Blank, Marion A.

AU - Chevrier, Marc

AU - Plevy, Scott

AU - Popp, John

AU - Cornillie, Freddy J.

AU - Lukas, Milan

AU - Danese, Silvio

AU - Gionchetti, Paolo

AU - Hanauer, Stephen B.

AU - Reinisch, Walter

AU - Sandborn, William J.

AU - Sorrentino, Dario

AU - Rutgeerts, Paul

AU - Debinski, H.

AU - Florin, T.

AU - Hetzel, D.

AU - Lawrance, I.

AU - Radford-Smith, G.

AU - Sloss, A.

AU - Gassner, S.

AU - Haas, T.

AU - Reicht, G.

AU - Strasser, M.

AU - Vogelsang, H.

AU - Bossuyt, P.

AU - Dewit, O.

AU - D'Haens, G.

AU - Franchimont, D.

AU - Louis, E.

AU - Vermeire, S.

AU - Bernstein, C. N.

AU - Bourdages, R.

AU - Chiba, N.

AU - Dhalla, S. S.

AU - Fedorak, R. N.

AU - Lachance, J. R.

AU - Panaccione, R.

AU - Ropeleski, M.

AU - Singh Salh, B.

AU - Colombel, J. F.

AU - Allez, M.

AU - Desreumaux, P.

AU - Dupas, J. L.

AU - Grimaud, J. C.

AU - Hebuterne, X.

AU - Laharie, D.

AU - Lerebours, E.

AU - Peyrin-Biroulet, L.

AU - Reimund, J. M.

AU - Viennot, S.

AU - Zerbib, F.

AU - Antoni, C.

AU - Atreya, R.

AU - Baumgart, D. C.

AU - Berg, C.

AU - Boecker, U.

AU - Bramkamp, G.

AU - Bünning, C.

AU - Ehehalt, R.

AU - Howaldt, S.

AU - Kucharzik, T.

AU - Lamprecht, H. G.

AU - Mudter, J.

AU - Preiss, J. C.

AU - Schreiber, S.

AU - Seidler, U.

AU - Altorjay, I.

AU - Banai, J.

AU - Lakatos, P. L.

AU - Varga, M.

AU - Vincze, A.

AU - Avni-Biron, I.

AU - Fishman, S.

AU - Fraser, G. M.

AU - Goldin, E.

AU - Rachmilewitz, D.

AU - Annese, V.

AU - Ardizzone, S.

AU - Biancone, L.

AU - Bossa, F.

AU - Fries, W.

AU - Maconi, G.

AU - Terrosu, G.

AU - Usai, P.

AU - D'Haens, G. R.

AU - Gearry, R. B.

AU - Hill, J.

AU - Rowbotham, D. S.

AU - Schultz, M.

AU - Stubbs, R. S.

AU - Wallace, D.

AU - Walmsley, R. S.

AU - Wyeth, J.

AU - Malecka-Panas, E.

AU - Paradowski, L.

AU - Regula, J.

AU - Beales, I. P.

AU - Campbell, S.

AU - Hawthorne, A. B.

AU - Parkes, M.

AU - Travis, S. P.

AU - Achkar, J. P.

AU - Behm, B. W.

AU - Bickston, S. J.

AU - Brown, K. J.

AU - Chiorean, M. V.

AU - Devilliers, W. J.S.

AU - Elliott, D. E.

AU - Grunkmeier, D.

AU - Hamilton, J. W.

AU - Hanson, J. S.

AU - Hardi, R.

AU - Helper, D. J.

AU - Herfarth, H.

AU - Higgins, P. D.R.

AU - Holderman, W. H.

AU - Kottoor, R.

AU - Kreines, M. D.

AU - Leman, B. I.

AU - Li, X.

AU - Loftus, E. V.

AU - Noar, M.

AU - Oikonomou, I.

AU - Onken, J.

AU - Peterson, K. A.

AU - Phillips, R. P.

AU - Randall, C. W.

AU - Ricci, M.

AU - Ritter, T.

AU - Rubin, D. T.

AU - Safdi, M.

AU - Sauberman, L.

AU - Scherl, E.

AU - Schwarz, R. P.

AU - Sedghi, S.

AU - Shafran, I.

AU - Sninsky, C. A.

AU - Stein, I.

AU - Swoger, J.

AU - Vecchio, J.

AU - Weinberg, D. I.

AU - Wruble, L. D.

AU - Yajnik, V.

AU - Younes, Z.

N1 - Funding Information: Conflicts of interest The authors disclose the following: Miguel Regueiro has received consulting fees from AbbVie, Janssen Biotech, Inc., Takeda, and UCB Pharma; served as a Scientific Advisory Board member for AbbVie, Janssen Biotech, Takeda, and UCB Pharma; and received research grants from AbbVie, Janssen Biotech, Takeda, and UCB Pharma. Brian G. Feagan has received consulting fees from Abbott/AbbVie, Actogenix, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Axcan, Baxter Healthcare Corp., Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech, LLC. (formerly Centocor, Inc.), Janssen Research & Development, LLC., Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Merck, Millennium, Nektar, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, Tillotts, UCB Pharma, Vertex Pharma, Warner-Chilcott, Wyeth, Zealand, Zyngenia; payments for lectures/speakers bureau from Abbott/AbbVie, Janssen Research & Development, LLC., Takeda, Warner-Chilcott and UCB Pharma; and served as a Scientific Advisory Board member for Avaxia Biologics Inc., Bristol-Myers Squibb, Celgene, Janssen Biotech, LLC. (formerly Centocor, Inc.), Elan/Biogen, Ferring, Janssen Research & Development, LLC., Merck, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, Tillotts Pharma AG and UCB Pharma Marion A. Blank and John Popp are employees of Janssen Scientific Affairs, LLC. Bin Zou and Scott Plevy are employees of Janssen Research & Development, LLC. Freddy J. Cornillie is currently an employee of MSD International and was an employee of Janssen Biologics BV, Leiden, The Netherlands during the study conduct. Silvio Danese has received consulting fees from AbbVie, Astra Zeneca, MSD, Takeda Millennium, Salix Pharmaceuticals, and Pfizer. Paolo Gionchetti has received consulting fees from AbbVie, MSD, and Takeda; and has received payments for speakers’ bureau from Ferring and Chiesi. Stephen B. Hanauer has received consulting fees from Janssen Research & Development, LLC., payments for speakers bureau participation from Janssen Research & Development, LLC., and served as a Scientific Advisory Board member for Janssen Research & Development, LLC. Walter Reinisch has served as a speaker, consultant, and/or advisory board member for Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Janssen Biotech, LLC. (formerly Centocor, Inc.), Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Grünenthal, Janssen Research & Development, LLC., Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zygenia, and 4SC. William J. Sandborn has received consulting fees from Abbott, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corp, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys Inc, Atlantic Healthcare Ltd, Aptalis, BioBalance Corp, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, EnGene Inc, Eli Lilly, Enteromedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexio Therapeutics Inc, Funxional Therapeutics Ltd, Genzyme Corp, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, Janssen Research & Development, LLC., KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera Corp, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millenium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Ltd, Purgenesis Technologies Inc, Relypsa Inc, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering Plough, Shire Pharmaceuticals, Sigmoid Pharma Ltd, Sirtris Pharmaceuticals, SLA Pharma UK Ltd, Targacept, Teva Pharmaceuticals, Therakos, Tilliotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Ltd, Warner Chilcott UK Ltd, and Wyeth; research grants from Abbott, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen Research & Development, LLC., Milennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals, and UCB Pharma; payments for lectures/speakers bureau from Abbott, Bristol-Myers Squibb, and Janssen Research & Development, LLC; and holds stock/stock options in Enteromedics. Dario Sorrentino has received consulting fees from Abbott/AbbVie, Schering-Plough, MSD, Janssen Research & Development, LLC., Centocor Inc., TechLab, Hoffmann-LaRoche, Giuliani, Schering-Plough, and Ferring; research grants from AbbVie, Janssen Research & Development, LLC, Schering-Plough, TechLab, Centocor and serves in the Speakers Bureau of AbbVie. Paul Rutgeerts has received research funding, and/or served as speaker, consultant and/or advisory board member for Abbott Laboratories, Janssen Research & Development, LLC., Merck Research Laboratories, Merck Serono, UCB Pharma, Millenium/Takeda, Genentech/Hoffman LaRoche, Neovacs, Bristol Myers Squibb, Robarts, Tillotts, Pfizer, and Falk Pharma. The remaining author discloses no conflicts. Publisher Copyright: © 2016 AGA Institute.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

KW - Anti-TNF

KW - CDAI

KW - Inflammatory Bowel Disease

KW - PREVENT

UR - http://www.scopus.com/inward/record.url?scp=84975815690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975815690&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2016.02.072

DO - 10.1053/j.gastro.2016.02.072

M3 - Article

C2 - 26946343

AN - SCOPUS:84975815690

SN - 0016-5085

VL - 150

SP - 1568

EP - 1578

JO - Gastroenterology

JF - Gastroenterology

IS - 7

ER -

Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease after Ileocolonic Resection

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