Novel Agents in Inflammatory Bowel Disease

  • Fernando VelayosEmail author


For nearly two decades, novel therapies for IBD have primarily targeted the same cell signaling cytokine, tumor necrosis factor alpha (TNF-α). TNF is a key cytokine in inflammatory pathways, and dysregulation of TNF production has been implicated in both ulcerative colitis (UC) and Crohn’s disease (CD). This strategy has been and continues to be effective but not wholly effective. Nearly a third of patients do not respond to this strategy and others flare despite initial control. This chapter focuses primarily on novel agents other than anti-TNFs that have either been recently released or under late-stage investigation and likely to progress to market.


Crohn’s Ulcerative colitis Biologic therapy Anti-integrin Janus kinase inhibitor Sphingosine-1-phosphate receptor inhibitor IL12/IL23 inhibitor Anti-SMAD7 


  1. 1.
    Dulai PS, Sandborn WJ. Next-generation therapeutics for inflammatory bowel disease. Curr Gastroenterol Rep. 2016;18:51.CrossRefPubMedGoogle Scholar
  2. 2.
    Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.CrossRefPubMedGoogle Scholar
  3. 3.
    Shahidi N, Bressler B, Panaccione R. The role of vedolizumab in patients with moderate-to-severe Crohn’s disease and ulcerative colitis. Therap Adv Gastroenterol. 2016;9:330–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cherry LN, Yunker NS, Lambert ER, Vaughan D, Lowe DK. Vedolizumab: an alpha4beta7 integrin antagonist for ulcerative colitis and Crohn’s disease. Ther Adv Chronic Dis. 2015;6:224–33.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Sandborn WJ, Colombel JF, Enns R, et al. Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2005;353:1912–25.CrossRefPubMedGoogle Scholar
  6. 6.
    Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366:1870–80.CrossRefPubMedGoogle Scholar
  7. 7.
    Cominelli F. Inhibition of leukocyte trafficking in inflammatory bowel disease. N Engl J Med. 2013;369:775–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369:711–21.CrossRefPubMedGoogle Scholar
  9. 9.
    Colombel JF, Sands BE, Rutgeerts P, et al. The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut. 2016;66(5):839–51.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Sands BE, Feagan BG, Rutgeerts P, et al. Effects of vedolizumab induction therapy for patients with Crohn’s disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014;147:618–27.e3.CrossRefPubMedGoogle Scholar
  11. 11.
    Armuzzi A, Felice C. Etrolizumab in moderate-to-severe ulcerative colitis. Lancet. 2014;384:285–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Vermeire S, O'Byrne S, Keir M, et al. Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet. 2014;384:309–18.CrossRefPubMedGoogle Scholar
  13. 13.
    Fiorino G, Gilardi D, Danese S. The clinical potential of etrolizumab in ulcerative colitis: hypes and hopes. Therap Adv Gastroenterol. 2016;9:503–12.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Reinisch W, Sandborn W, Danese S, et al. A randomized, multicenter double-blind, placebo-controlled study of the safety and efficacy of anti-MAdCAM antibody PF-00547659 (PF) in patients with moderate to severe ulcerative colitis: results of the TURANDOT study. Gastroenterology. 2015;148:S1193–5.CrossRefGoogle Scholar
  15. 15.
    Khanna R, Feagan BG. Emerging therapies for inflammatory bowel diseases. Dig Dis. 2016;34(Suppl 1):67–73.CrossRefPubMedGoogle Scholar
  16. 16.
    Sandborn W, Lee SD, Tarabar D, et al. Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn’s disease: results of the OPERA study. Gastroenterology. 2015;148:S162-S.CrossRefGoogle Scholar
  17. 17.
    Reinisch W, Vermeire S, Cataldi F, et al. Anti-MAdCAM monoclonal antibody PF-00547659 does not affect immune surveillance in the central nervous system of crohn’s disease patients who are anti-TNF inadequate responders: results from the Tosca study. Gastroenterology. 2014;146:S150-S.CrossRefGoogle Scholar
  18. 18.
    Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med. 2016;374:1754–62.CrossRefPubMedGoogle Scholar
  19. 19.
    Nielsen OH, Seidelin JB, Ainsworth M, Coskun M. Will novel oral formulations change the management of inflammatory bowel disease? Expert Opin Investig Drugs. 2016;25:709–18.CrossRefPubMedGoogle Scholar
  20. 20.
    Sanchez T, Hla T. Structural and functional characteristics of S1P receptors. J Cell Biochem. 2004;92:913–22.CrossRefPubMedGoogle Scholar
  21. 21.
    Teng MW, Bowman EP, McElwee JJ, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;21:719–29.CrossRefPubMedGoogle Scholar
  22. 22.
    Deepak P, Loftus EV Jr. Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy. Drug Des Devel Ther. 2016;10:3685–98.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Chan HC, Ng SC. Emerging biologics in inflammatory bowel disease. J Gastroenterol. 2017;52:141–50.CrossRefPubMedGoogle Scholar
  24. 24.
    Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med. 2012;367:1519–28.CrossRefPubMedGoogle Scholar
  25. 25.
    Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375:1946–60.CrossRefPubMedGoogle Scholar
  26. 26.
    Feagan BG, Sandborn W, Panes J, et al. Efficacy and safety of induction therapy with the selective IL-23 inhibitor BI 655066, in patients with moderate-to-severe Crohn’s disease: results of a randomized, double-blind, placebo-controlled phase II study. Gastroenterology. 2016;150:S1266-S.CrossRefGoogle Scholar
  27. 27.
    Reichert JM. Antibodies to watch in 2017. MAbs. 2017;9:167–81.CrossRefPubMedGoogle Scholar
  28. 28.
    Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77(5):521–46.CrossRefPubMedGoogle Scholar
  29. 29.
    Feagan B. Update on tofacitinib for inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2016;12:572–4.Google Scholar
  30. 30.
    Sandborn WJ, Sands BE, D'Haens G, et al. Efficacy and safety of oral tofacitinib as induction therapy in patients with moderate-to-severe ulcerative colitis: results from 2 phase 3 randomised controlled trials. J Crohns Colitis. 2016;10:S15-S.CrossRefGoogle Scholar
  31. 31.
    Sandborn W, Sands B, Danese S, et al. Efficacy and safety of oral tofacitinib as maintenance therapy in patients with moderate to severe ulcerative colitis: results from a phase 3 randomised controlled trial. J Crohns Colitis. 2017;10:S15-S.Google Scholar
  32. 32.
    Panes J, Sandborn WJ, Schreiber S, et al. Tofacitinib for induction and maintenance therapy of Crohn’s disease: results of two phase IIb randomised placebo-controlled trials. Gut. 2017;66(6):1049–59.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Vermeire S, Schreiber S, Petryka R, et al. Clinical remission in patients with moderate-to-severe Crohn’s disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial. Lancet. 2017;389:266–75.CrossRefPubMedGoogle Scholar
  34. 34.
    Ardizzone S, Bevivino G, Monteleone G. Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn’s disease. Therap Adv Gastroenterol. 2016;9:527–32.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Monteleone G, Neurath MF, Ardizzone S, et al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn’s disease. N Engl J Med. 2015;372:1104–13.CrossRefPubMedGoogle Scholar
  36. 36.
    Monteleone G, Kumberova A, Croft NM, McKenzie C, Steer HW, MacDonald TT. Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Invest. 2001;108:601–9.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Vermeire S. Oral SMAD7 antisense drug for Crohn’s disease. N Engl J Med. 2015;372:1166–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Center for Crohn’s and ColitisUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations