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Table of Contents
Vol. 30, Suppl. 3, 2012
Issue release date: January 2013
Section title: Biologicals and Beyond
Dig Dis 2012;30(suppl 3):140–144
(DOI:10.1159/000342742)

The Future of Inflammatory Bowel Disease Therapy: Where Do We Go from Here?

Sandborn W.J.
Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, Calif., USA

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Article / Publication Details

First-Page Preview
Abstract of Biologicals and Beyond

Published online: 1/3/2013

Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 0

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: http://www.karger.com/DDI

Abstract

There are six important trends that will impact the future of inflammatory bowel disease therapy. (1) Increased use of the biomarkers C-reactive protein (CRP) and fecal calprotectin, and increased imaging with colonoscopy and MRI enterography. (2) Increased use of pharmacokinetics to customize drug dosing for individual patients. Multiple factors impact the pharmacokinetics of monoclonal antibodies including the presence of antidrug antibodies, concomitant immunosuppression and low serum albumin and high CRP concentrations. (3) Evolution of treatment end points from symptoms to deep remission (a combination of both clinical remission and mucosal healing) to the prevention of bowel damage (in Crohn’s disease) and surgery in the short-to-intermediate term and prevention of disability in the longer term. (4) Evolving data demonstrate that azathioprine monotherapy is minimally effective as a disease modification agent in Crohn’s disease. Use of azathioprine as a monotherapy will decline. (5) Combination therapy with azathioprine and infliximab is superior to monotherapy with either agent. Use of combination therapy will increase. (6) There is a rich pipeline of novel therapeutic agents. Treatment strategies that appear particularly appealing include selective anti-integrin therapy with vedolizumab (anti-α4β7), etrolizumab (anti-β7 antibody) and PF-00547,659 (anti-MAdCAM-1 antibody), anti-interleukin 12/23p40 therapy with ustekinumab and Janus kinase 1, 2 and 3 inhibition with toafacitinib.


Article / Publication Details

First-Page Preview
Abstract of Biologicals and Beyond

Published online: 1/3/2013

Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 0

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: http://www.karger.com/DDI


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Modigliani R, Mary JY, Simon JF, Cortot A, Soule JC, Gendre JP, Rene E: Clinical, biological, and endoscopic picture of attacks of Crohn’s disease. Evolution on prednisolone. Groupe d’Etude Thérapeutique des Affections Inflammatoires Digestives. Gastroenterology 1990;98:811–818.
  2. Jones J, Loftus EV Jr, Panaccione R, Chen LS, Peterson S, McConnell J, Baudhuin L, Hanson K, Feagan BG, Harmsen SW, Zinsmeister AR, Helou E, Sandborn WJ: Relationships between disease activity and serum and fecal biomarkers in patients with Crohn’s disease. Clin Gastroenterol Hepatol 2008;6:1218–1224.
  3. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D’Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P: Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010;362:1383–1395.
  4. Ordas I, Mould DR, Feagan BG, Sandborn WJ: Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther 2012;91:635–646.
  5. Ordas I, Feagan BG, Sandborn WJ: Drug monitoring of TNF antagonists in inflammatory bowel disease. Clin Gastroenterol Hepatol 2012, in press.
  6. Baert F, Noman M, Vermeire S, Van Assche G, G DH, Carbonez A, Rutgeerts P: Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med 2003;348:601–608.
  7. Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR: Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut 2010;59:49–54.
  8. Maser EA, Villela R, Silverberg MS, Greenberg GR: Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol 2006;4:1248–1254.
  9. Fasanmade AA, Adedokun OJ, Olson A, Strauss R, Davis HM: Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis. Int J Clin Pharmacol Ther 2010;48:297–308.
  10. Sandborn WJ, Rutgeerts P, Feagan BG, Reinisch W, Olson A, Johanns J, Lu J, Horgan K, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF: Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology 2009;137:1250–1260;quiz 1520.
  11. Colombel JF, Rutgeerts P, Reinisch W, Esser D, Wang Y, Lang Y, Marano CW, Strauss R, Oddens BJ, Feagan BG, Hanauer SB, Lichtenstein GR, Present D, Sands BE, Sandborn WJ: Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology 2011;141:1194–1201.
  12. Pariente B, Cosnes J, Danese S, Sandborn WJ, Lewin M, Fletcher JG, Chowers Y, D’Haens G, Feagan BG, Hibi T, Hommes DW, Irvine EJ, Kamm MA, Loftus EV Jr, Louis E, Michetti P, Munkholm P, Oresland T, Panes J, Peyrin-Biroulet L, Reinisch W, Sands BE, Schoelmerich J, Schreiber S, Tilg H, Travis S, van Assche G, Vecchi M, Mary JY, Colombel JF, Lemann M: Development of the Crohn’s disease digestive damage score, the Lémann score. Inflamm Bowel Dis 2011;17:1415–1422.
  13. Peyrin-Biroulet L, Cieza A, Sandborn WJ, Coenen M, Chowers Y, Hibi T, Kostanjsek N, Stucki G, Colombel JF: Development of the first disability index for inflammatory bowel disease based on the international classification of functioning, disability and health. Gut 2012;61:241–247.
  14. Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, Gendre JP: Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis 2002;8:244–250.
  15. Munkholm P, Langholz E, Davidsen M, Binder V: Intestinal cancer risk and mortality in patients with Crohn’s disease. Gastroenterology 1993;105:1716–1723.
  16. Cosnes J, de Parades V, Carbonnel F, Beaugerie L, Ngo Y, Gendre JP, Sezeur A, Gallot D, Malafosse M, le Quintrec Y: Classification of the sequelae of bowel resection for Crohn’s disease. Br J Surg 1994;81:1627–1631.
  17. Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Hanauer SB: Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease [see comment]. Gastroenterology 2004;126:402–413.
  18. D’Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van de Mierop FJ, Coche JC, van der Woude J, Ochsenkuhn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 2008;371:660–667.
  19. Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, Stokkers P, Hommes D, Rutgeerts P, Vermeire S, D’Haens G: Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology 2010;138:463–468;quiz e10–11.
  20. Colombel JF, Rutgeerts PJ, Sandborn WJ, Camez AA, Pollack PF, Chen N, Yang M, Mulani P, Chao JD: Adalimumab treatment results in deep remission for patients with moderate to severe ileocolonic Crohn’s disease: results from EXTEND. Gastroenterology 2010;138(suppl 1):S-518.
  21. Colombel JF, Rutgeerts P, Sandborn WJ, Yang M, Lomax KG, Pollack PF, Thakkar R, Camez A, Chen N, Mulani PM, Chao J: Deep remission predicts long-term outcomes for adalimumab-treated patients wiht Crohn’s disease: data from EXTEND. Gut 2010;59 (suppl 3):A80 (OP371).
  22. Sans M, López-San Román A, Esteve M, Bermejo F, García-Sánchez V, Torres Y, Domenech E, Piqueras M, Aceituno M, Gomez-Garcia M, Taxonera C, Gisbert JP, Gutiérrez A, Gomollón F, Ginard D, Bernal A, Gimeno-García AZ, Muñoz C, Mearin F, Minguez M, Barreiro-de Acosta M, Calvet X, Buenestado J, Merino O, Barrachina M, Bujanda L, Mañosa M, Calvo MM, García E, Montoro MA, Justiniano JMH, Andreu M, Hernandez V, Hinojosa J, Panes J: Early use of azathioprine has a steroid sparing effect on recently diagnosed Crohn’s disease patients. Gastroenterology 2011;140(suppl 1):S-109.
  23. Cosnes J, Bourrier A, Bouhnik Y, Laharie D, Nahon S, Bonnet J, Getaid G, Carbonnel F, Dupas J, Jean Marie R, Jouet P, Savoye G, Mary J, Colombel J: Accelerated step-care therapy with early azathioprine (AZA) vs. conventional step-care in Crohn’s disease. A randomized study. Gastroenterology 2012;142(suppl 1):S-161.
  24. Markowitz J, Grancher K, Kohn N, Lesser M, Daum F: A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology 2000;119:895–902.
  25. Panaccione R, Ghosh S, Middleton S, Márquez JR, Khalif I, Flint L, van Hoogstraten HJF, Zheng H, Danese S, Rutgeerts P: Infliximab, azathioprine, or infliximab + azathioprine for treatment of moderate to severe ulcerative colitis: UC SUCCESS trial. Gastroenterology 2011;140:S-134,abstract 835.
  26. Lichtenstein GR, Diamond RH, Wagner CL, Fasanmade AA, Olson AD, Marano CW, Johanns J, Lang Y, Sandborn WJ: Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther 2009;30:210–226.
  27. Peyrin-Biroulet L, Desreumaux P, Sandborn WJ, Colombel JF: Crohn’s disease: beyond antagonists of tumour necrosis factor. Lancet 2008;372:67–81.
  28. Feagan BG, Greenberg GR, Wild G, Fedorak R, Pare P, McDonald JWD, Dube R, Cohen A, Steinhardt H, Landau S, Aguzzi RA, Fox IH, Vandervoort MK: Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med 2005;352:2499–2507.
  29. Feagan BG, Greenberg GR, Wild G, Fedorak RN, Pare P, McDonald JW, Cohen A, Bitton A, Baker J, Dube R, Landau SB, Vandervoort MK, Parikh A: Treatment of active Crohn’s disease with MLN0002, a humanized antibody to the alpha4beta7 integrin. Clin Gastroenterol Hepatol 2008;6:1370–1377.
  30. Feagan BG, Rutgeerts PJ, Sands BE, Colombel J, Sandborn WJ, Hanauer SB, Van Assche GA, Axler J, Kim H, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A: Induction therapy for ulcerative colitis: results of GEMINI I, a randomized, placebo-controlled, double-blind, multicenter phase 3 trial. Gastroenterology 2012;142(suppl 1):160–161.
  31. Rutgeerts PJ, Fedorak RN, Hommes DW, Sturm A, Baumgart DC, Bressler B, Schreiber S, Mansfield JC, Williams M, Tang M, Visich J, Wei X, Keir M, Luca D, Danilenko D, Egen J, O’Byrne S: A randomised phase I study of etrolizumab (rhuMAb beta7) in moderate to severe ulcerative colitis. Gut 2012, E-pub ahead of print.
  32. Vermeire S, Ghosh S, Panes J, Dahlerup JF, Luegering A, Sirotiakova J, Strauch U, Burgess G, Spanton J, Martin SW, Niezychowski W: The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study. Gut 2011;60:1068–1075.
  33. Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, Johanns J, Blank M, Rutgeerts P: A randomized trial of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn’s disease. Gastroenterology 2008;135:1130–1141.
  34. Sandborn WJ, Gasink C, Gao LL, Blank M, Johanns J, Guzzo C, Sands BE, Hanauer SB, Targan SR, Rutgeerts PJ, Ghosh S, de Villiers W, Panaccione R, Greenberg GR, Schreiber S, Lichtiger S, Feagan BG: A multicenter, randomized, double-blind, placebo-controlled phase 2b study of ustekinumab, a human monoclonal antibody to IL-12/23p40, in patients with moderately to severely active Crohn’s disease: results through week 22 from the Certifi trial. Gastroenterology 2011;140(suppl 1):S-109.
  35. Sandborn WJ, Ghosh S, Panes J, Vranic I, Su C, Spanton J, Niezychowski W: Phase 2 study of CP-690,550, an oral Janus kinase inhibitor, in active ulcerative colitis. Gastroenterology 2011;140(suppl 1):S-110.