Top

Current Treatment Options in Gastroenterology

Published in:

01-03-2018 | Inflammatory Bowel Disease (G Lichtenstein, Section Editor)

Novel Therapies and Treatment Strategies for Patients with Inflammatory Bowel Disease

Authors: Marjolijn Duijvestein, MD, PhD, Robert Battat, MD, Niels Vande Casteele, PharmD, PhD, Geert R. D’Haens, MD, PhD, William J. Sandborn, MD, Reena Khanna, MD, Vipul Jairath, MD, PhD, Brian G. Feagan, MD

Published in: Current Treatment Options in Gastroenterology | Issue 1/2018

Abstract

Purpose of review

This article reviews current treatment options and strategies and provides an update on the status of drug development programs of new therapeutic agents for inflammatory bowel diseases (IBD).

Recent findings

In the past two decades, tumor necrosis factor antagonist therapy has given clinicians better treatment options. However, not all patients respond to induction therapy with these agents, and of those initially responding, up to 40% ultimately lose response due to suboptimal drug exposure (e.g., caused by immunogenicity), side effects, or other poorly characterized mechanisms. Recently, additional therapies, such as vedolizumab, an integrin blocker that prevents T cell trafficking to the gut, and ustekinumab, an antibody blocking the common p40 subunit of interleukin (IL)-12 and 23, were introduced to the market. In addition, other agents including novel anti-trafficking therapies (e.g., anti-β7 and sphingosine-1-phosphate receptor modulators), antibodies against p19 (unique to IL-23), and small molecules including Janus kinase inhibitors are under investigation in phase II and III trials.

Furthermore, the management of IBD has evolved from targeting control of symptoms to suppression of mucosal inflammation. This shift in thinking has been accompanied by the early use of highly effective therapy in poor prognosis patients, accelerated treatment escalation and utilization of a treat to target paradigm approach, and adoption of therapeutic drug monitoring.

Summary

The treatment landscape for IBD is rapidly evolving with the recent approval of novel biologics as well as several other agents in late phase of clinical development. Moreover, we have started to use agents more intelligently with a focus on risk stratification and early use of highly effective therapy in high-risk patients, treat to target using patient-reported outcomes (PROs), biomarkers, endoscopy, and therapeutic drug monitoring.

Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066–78.CrossRefPubMedPubMedCentral

Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ. Long-term complications, extraintestinal manifestations, and mortality in adult Crohn’s disease in population-based cohorts. Inflamm Bowel Dis. 2011;17(1):471–8.CrossRefPubMed

Van Deventer SJ. Tumour necrosis factor and Crohn’s disease. Gut. 1997;40(4):443–8.CrossRefPubMedPubMedCentral

•• Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110(9):1324–38. This article provides evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD.CrossRefPubMed

Wang Y, Parker CE, Bhanji T, Feagan BG, JK MD. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2016;4:CD000543.PubMed

Wang Y, Parker CE, Feagan BG, MacDonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2016;(5):Cd000544.

Lim WC, Wang Y, JK MD, Hanauer S. Aminosalicylates for induction of remission or response in Crohn’s disease. Cochrane Database Syst Rev. 2016;7:CD008870.PubMed

Sherlock ME, Seow CH, Steinhart AH, Griffiths AM. Oral budesonide for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2010;10:CD007698.

Sandborn WJ, Travis S, Moro L, Jones R, Gautille T, Bagin R, et al. Once-daily budesonide MMX(R) extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology. 2012;143(5):1218–26 e1–2.CrossRefPubMed

10.

Travis SP, Danese S, Kupcinskas L, Alexeeva O, D’haens G, Gibson PR, et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study. Gut. 2014;63(3):433–41.CrossRefPubMed

11.

Lichtenstein GR, Bengtsson B, Hapten-White L, Rutgeerts P. Oral budesonide for maintenance of remission of Crohn’s disease: a pooled safety analysis. Aliment Pharmacol Ther. 2009;29(6):643–53.CrossRefPubMed

12.

Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017;357:j1415.CrossRefPubMed

13.

Benchimol EI, Seow CH, Steinhart AH, Griffiths AM. Traditional corticosteroids for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2008;2:CD006792.

14.

D’Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet. 2008;371(9613):660–7.CrossRefPubMed

15.

JW MD, Tsoulis DJ, Macdonald JK, Feagan BG. Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev. 2012;12:CD003459.

16.

Feagan BG, Rochon J, Fedorak RN, Irvine EJ, Wild G, Sutherland L, et al. Methotrexate for the treatment of Crohn’s disease. The North American Crohn’s Study Group Investigators. N Engl J Med. 1995;332(5):292–7.CrossRefPubMed

17.

Soon SY, Ansari A, Yaneza M, Raoof S, Hirst J, Sanderson JD. Experience with the use of low-dose methotrexate for inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2004;16(9):921–6.CrossRefPubMed

18.

Panés J, López-SanRomán A, Bermejo F, García-Sánchez V, Esteve M, Torres Y, et al. Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn’s disease. Gastroenterology. 2013;145(4):766–74.e1.CrossRefPubMed

19.

Cosnes J, Bourrier A, Laharie D, Nahon S, Bouhnik Y, Carbonnel F, et al. Early administration of azathioprine vs conventional management of Crohn’s Disease: a randomized controlled trial. Gastroenterology. 2013;145(4):758–65.e2. quiz e14–5

20.

Vande Casteele N, Herfarth H, Katz J, Falck-Ytter Y, Singh S. American Gastroenterological Association Institute technical review on the role of therapeutic drug monitoring in the management of inflammatory bowel diseases. Gastroenterology. 2017;153(3):835–57. e6

21.

Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Langholff W, et al. Drug therapies and the risk of malignancy in Crohn’s disease: results from the TREAT Registry. Am J Gastroenterol. 2014;109(2):212–23.CrossRefPubMed

22.

Kotlyar DS, Lewis JD, Beaugerie L, Tierney A, Brensinger CM, Gisbert JP, et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis. Clin Gastroenterol Hepatol. 2015;13(5):847–58 e4.CrossRefPubMed

23.

Smith MA, Irving PM, Marinaki AM, Sanderson JD. Review article: malignancy on thiopurine treatment with special reference to inflammatory bowel disease. Aliment Pharmacol Ther. 2010;32(2):119–30.CrossRefPubMed

24.

Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541–9.CrossRefPubMed

25.

Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007;357(3):239–50.CrossRefPubMed

26.

Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132(1):52–65.CrossRefPubMed

27.

Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):85–95. quiz e14–5

28.

Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138(2):463–8. quiz e10–1

29.

Behm BW, Bickston SJ. Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev. 2008;1:CD006893.

30.

Danese S, Fiorino G, Reinisch W. Review article: Causative factors and the clinical management of patients with Crohn’s disease who lose response to anti-TNF-alpha therapy. Aliment Pharmacol Ther. 2011;34(1):1–10.CrossRefPubMed

31.

Singh JA, Wells GA, Christensen R, Tanjong Ghogomu E, Maxwell L, Macdonald JK, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2:CD008794.

32.

Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuk S, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72(10):1613–20.CrossRefPubMedPubMedCentral

33.

Park W, Hrycaj P, Jeka S, Kovalenko V, Lysenko G, Miranda P, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis. 2013;72(10):1605–12.CrossRefPubMedPubMedCentral

34.

•• Jorgensen KK, Olsen IC, Goll GL, Lorentzen M, Bolstad N, Haavardsholm EA, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2017;389(10086):2304–16. First prospective randomized trial on switching from originator infliximab to biosimilar.CrossRefPubMed

35.

Khanna R, Zou G. Is a biosimilar interchangeable with an originator? Gastroenterology. 2017;153(4):1160–2.CrossRefPubMed

36.

FDA. Considerations in demonstrating interchangeability with a reference product. 2017.

37.

Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870–80.CrossRefPubMed

38.

Berlin C, Berg EL, Briskin MJ, Andrew DP, Kilshaw PJ, Holzmann B, et al. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993;74(1):185–95.CrossRefPubMed

39.

Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699–710.CrossRefPubMed

40.

Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369(8):711–21.CrossRefPubMed

41.

Sands BE, Feagan BG, Rutgeerts P, Colombel JF, Sandborn WJ, Sy R, et al. Effects of vedolizumab induction therapy for patients with Crohn’s disease in whom tumor necrosis factor antagonist treatment had failed. Gastroenterology. 2014;147(3):618–27 e3.CrossRefPubMed

42.

Khanna R, Zou G, Stitt L, Feagan BG, Sandborn WJ, Rutgeerts P, et al. Responsiveness of endoscopic indices of disease activity for Crohn’s disease. Am J Gastroenterol. 2017;

43.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314(5804):1461–3.CrossRefPubMedPubMedCentral

44.

Wang X, Wu T, Zhou F, Liu S, Zhou R, Zhu S, et al. IL12p40 regulates functional development of human CD4+ T cells: enlightenment by the elevated expressions of IL12p40 in patients with inflammatory bowel diseases. Medicine (Baltimore). 2015;94(10):e613.CrossRef

45.

Maxwell JR, Zhang Y, Brown WA, Smith CL, Byrne FR, Fiorino M, et al. Differential roles for interleukin-23 and interleukin-17 in intestinal immunoregulation. Immunity. 2015;43(4):739–50.CrossRefPubMed

46.

•• Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375(20):1946–60. Phase III results on ustekinumab for CD.CrossRefPubMed

47.

• Gottlieb AB, Kalb RE, Langley RG, Krueger GG, de Jong EM, Guenther L, et al. Safety observations in 12,095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies. J Drugs Dermatol. 2014;13(12):1441–8. Safety observations obtained in an international registry (PSOLAR) concerning biologic therapy.PubMed

48.

Papp KA, Griffiths CE, Gordon K, Lebwohl M, Szapary PO, Wasfi Y, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol. 2013;168(4):844–54.CrossRefPubMed

49.

Tillack C, Ehmann LM, Friedrich M, Laubender RP, Papay P, Vogelsang H, et al. Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-gamma-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment. Gut. 2014;63(4):567–77.CrossRefPubMed

50.

Deepak P, Sandborn WJ. Ustekinumab and anti-interleukin-23 agents in Crohn’s disease. Gastroenterol Clin N Am. 2017;46(3):603–26.CrossRef

51.

Thomas S, Baumgart DC. Targeting leukocyte migration and adhesion in Crohn’s disease and ulcerative colitis. Inflammopharmacology. 2012;20(1):1–18.CrossRefPubMed

52.

•• Vermeire S, O’Byrne S, Keir M, Williams M, Lu TT, Mansfield JC, et al. Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet. 2014;384(9940):309–18. Phase II results on etroluzimab for UC.CrossRefPubMed

53.

Mullershausen F, Zecri F, Cetin C, Billich A, Guerini D, Seuwen K. Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat Chem Biol. 2009;5(6):428–34.CrossRefPubMed

54.

Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.CrossRefPubMed

55.

Camm J, Hla T, Bakshi R, Brinkmann V. Cardiac and vascular effects of fingolimod: mechanistic basis and clinical implications. Am Heart J. 2014;168(5):632–44.CrossRefPubMed

56.

•• Sandborn WJ, Feagan BG, Wolf DC, D’Haens G, Vermeire S, Hanauer SB, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med. 2016;374(18):1754–62. Phase II results on ozanimod for UC.CrossRefPubMed

57.

Fuss IJ, Becker C, Yang Z, Groden C, Hornung RL, Heller F, et al. Both IL-12p70 and IL-23 are synthesized during active Crohn’s disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. Inflammatory Bowel Diseases. 2006;12(1):9–15.CrossRefPubMed

58.

Coskun M, Vermeire S, Nielsen OH. Novel targeted therapies for inflammatory bowel disease. Trends Pharmacol Sci. 2017;38(2):127–42.CrossRefPubMed

59.

Teng MW, Bowman EP, JJ ME, Smyth MJ, Casanova JL, Cooper AM, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;21(7):719–29.CrossRefPubMed

60.

•• Feagan BG, Sandborn WJ, D’Haens, G, Panes J, Kaser A, Ferrante M, et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017. Phase II results on risankizumab for CD.

61.

•• Sands BE, Chen J, Feagan BG, Penney M, Rees WA, Danese S, et al. Efficacy and safety of MEDI2070, an antibody against interleukin 23, in patients with moderate to severe Crohn’s disease: a phase 2a study. Gastroenterology. 2017;153(1):77–86 e6. Phase II results on brazikumab for CD.CrossRefPubMed

62.

Jostins L, Ripke S, Weersma RK, Duerr RH, DP MG, Hui KY, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119–24.CrossRefPubMedPubMedCentral

63.

Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228(1):273–87.CrossRefPubMedPubMedCentral

64.

Boland BS, Vermeire S. Janus kinase antagonists and other novel small molecules for the treatment of Crohn’s disease. Gastroenterol Clin N Am. 2017;46(3):627–44.CrossRef

65.

•• Sandborn WJ, Su C, Sands BE, D’Haens GR, Vermeire S, Schreiber S, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376(18):1723–36. Phase III results on tofacitinib for UC.CrossRefPubMed

66.

•• Vermeire S, Schreiber S, Petryka R, Kuehbacher T, Hebuterne X, Roblin X, 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(10066):266–75. Phase II results on filgotinib for CD.CrossRefPubMed

67.

Sandborn WJ, Feagan BG, Panes J, D’Haens GR, Colombel JF, Zhou Q, et al. Safety and efficacy of ABT-494 (upadacitinib), an oral Jak1 inhibitor, as induction therapy in patients with Crohn’s disease: results from Celest. Gastroenterology. 152(5):S1308–S9.

68.

Peyrin-Biroulet L, Panes J, Sandborn WJ, Vermeire S, Danese S, Feagan BG, et al. Defining disease severity in inflammatory bowel diseases: current and future directions. Clin Gastroenterol Hepatol. 2016;14(3):348–54.e17.CrossRefPubMed

69.

Guizzetti L, Zou G, Khanna R, Dulai PS, Sandborn WJ, Jairath V, et al. Development of clinical prediction models for surgery and complications in Crohn’s disease. J Crohns Colitis. 2017.

70.

Beaugerie L, Seksik P, Nion-Larmurier I, Gendre JP, Cosnes J. Predictors of Crohn’s disease. Gastroenterology. 2006;130(3):650–6.CrossRefPubMed

71.

Loly C, Belaiche J, Louis E. Predictors of severe Crohn’s disease. Gastroenterol Clin N Am. 2007;132(Suppl 2):A-17.

72.

Khanna R, Jairath V, Feagan BG. The evolution of treatment paradigms in Crohn’s disease: beyond better drugs. Gastroenterol Clin N Am. 2017;46(3):661–77.CrossRef

73.

Van Assche G, Dignass A, Panes J, Beaugerie L, Karagiannis J, Allez M, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. J Crohns Colitis. 2010;4(1):7–27.CrossRefPubMed

74.

Yarur AJ, Strobel SG, Deshpande AR, Abreu MT. Predictors of aggressive inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011;7(10):652–9.

75.

Solberg IC, Vatn MH, Hoie O, Stray N, Sauar J, Jahnsen J, et al. Clinical course in Crohn’s disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Hepatol. 2007;5(12):1430–8.CrossRefPubMed

76.

Jess T, Riis L, Vind I, Winther KV, Borg S, Binder V, et al. Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark. Inflamm Bowel Dis. 2007;13(4):481–9.CrossRefPubMed

77.

Schreiber S, Reinisch W, Colombel JF, Sandborn WJ, Hommes DW, Robinson AM, et al. Subgroup analysis of the placebo-controlled CHARM trial: increased remission rates through 3 years for adalimumab-treated patients with early Crohn’s disease. J Crohns Colitis. 2013;7(3):213–21.CrossRefPubMed

78.

Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–95.CrossRefPubMed

79.

• Khanna R, Bressler B, Levesque BG, Zou G, Stitt LW, Greenberg GR, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomised controlled trial. Lancet. 2015;386(10006):1825–34. This prospective study demonstrates that although early combinedimmunosuppression (TNF antagonist and antimetabolite) was not more effective than conventional management for controlling Crohn’s disease symptoms, the risk of major adverse outcomes was lower.CrossRefPubMed

80.

Khanna R, Zou G, DHaens G, Feagan BG, Sandborn WJ, Vandervoort MK, et al. A retrospective analysis: the development of patient reported outcome measures for the assessment of Crohn’s disease activity. Aliment Pharmacol Ther. 2015;41(1):77–86.CrossRefPubMed

81.

Jairath V, Khanna R, Zou GY, Stitt L, Mosli M, Vandervoort MK, et al. Development of interim patient-reported outcome measures for the assessment of ulcerative colitis disease activity in clinical trials. Aliment Pharmacol Ther. 2015;42(10):1200–10.CrossRefPubMed

82.

Froslie KF, Jahnsen J, Moum BA, Vatn MH, Group I. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133(2):412–22.CrossRefPubMed

83.

Colombel JF, Rutgeerts PJ, Sandborn WJ, Yang M, Camez A, Pollack PF, et al. Adalimumab induces deep remission in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2014;12(3):414–22.e5.CrossRefPubMed

84.

• Shah SC, Colombel JF, Sands BE, Narula N. Mucosal healing is associated with improved long-term outcomes of patients with ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2016;14(9):1245–55 e8. A meta-analysis showing that mucosal healing is with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission.CrossRefPubMed

85.

Colombel JF, Rutgeerts P, Reinisch W, Esser D, Wang Y, Lang Y, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141(4):1194–201.CrossRefPubMed

86.

Bryant RV, Burger DC, Delo J, Walsh AJ, Thomas S, von Herbay A, et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2016;65(3):408–14.CrossRefPubMed

87.

• Christensen B, Hanauer SB, Erlich J, Kassim O, Gibson PR, Turner JR, et al. Histologic normalization occurs in ulcerative colitis and is associated with improved clinical outcomes. Clin Gastroenterol Hepatol. 2017. Histological remission better predicts lower rates of corticosteroid use and acute severe colitis requiring hospitalization, over a median of 6 years of follow-up.

88.

Mosli MH, Feagan BG, Zou G, Sandborn WJ, D’Haens G, Khanna R, et al. Development and validation of a histological index for UC. Gut. 2017;66(1):50–8.CrossRefPubMed

89.

D’Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P. Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998;114(2):262–7.CrossRefPubMed

90.

Mojtahed A, Khanna R, Sandborn WJ, D’Haens GR, Feagan BG, Shackelton LM, et al. Assessment of histologic disease activity in Crohn’s disease: a systematic review. Inflamm Bowel Dis. 2014;20(11):2092–103.CrossRefPubMed

91.

Brennan GT, Melton SD, Spechler SJ, Feagins LA. Clinical implications of histologic abnormalities in ileocolonic biopsies of patients with Crohn’s disease in remission. J Clin Gastroenterol. 2017;51(1):43–8.CrossRefPubMed

92.

Solem CA, Loftus EV Jr, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflammatory Bowel Disease. 2005;11(8):707–12.CrossRef

93.

Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, et al. C-reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis. Am J Gastroenterol. 2015;110(6):802–19. quiz 20

94.

Jones J, Loftus EV Jr, Panaccione R, Chen LS, Peterson S, McConnell J, et al. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2008;6(11):1218–24.CrossRefPubMed

95.

• Colombel JF, Panaccione R, Bossuyt P, Lukas M, Baert F, Vanasek T, et al. Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet. 2018;390(10114):2779–89. The first study to show that timely escalation with an anti-tumor necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early CD results in better clinical and endoscopic outcomes than symptom-driven decisions alone.CrossRefPubMed

96.

• Feuerstein JD, Nguyen GC, Kupfer SS, Falck-Ytter Y, Singh S, American Gastroenterological Association Institute Clinical Guidelines C. American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017;153(3):827–34. Current guideline of the American Gastroenterological Association Institute on therapeutic drug monitoring in IBD.CrossRefPubMed

97.

Coskun M, Steenholdt C, de Boer NK, Nielsen OH. Pharmacology and optimization of thiopurines and methotrexate in inflammatory bowel disease. Clin Pharmacokinet. 2016;55(3):257–74.CrossRefPubMed

98.

Bortlik M, Duricova D, Malickova K, Machkova N, Bouzkova E, Hrdlicka L, et al. Infliximab trough levels may predict sustained response to infliximab in patients with Crohn’s disease. J Crohn’s Colitis. 2013;7(9):736–43.CrossRef

99.

Adedokun OJ, Sandborn WJ, Feagan BG, Rutgeerts P, Xu Z, Marano CW, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014;147(6):1296–307 e5.CrossRefPubMed

100.

American Gastroenterological A. Therapeutic drug monitoring in inflammatory bowel disease: clinical decision support tool. Gastroenterology. 2017;153(3):858–9.CrossRef

101.

Beigel F, Friedrich M, Probst C, Sotlar K, Goke B, Diegelmann J, et al. Oncostatin M mediates STAT3-dependent intestinal epithelial restitution via increased cell proliferation, decreased apoptosis and upregulation of SERPIN family members. PloS One. 2014;9(4):e93498.CrossRefPubMedPubMedCentral

102.

• West NR, Hegazy AN, Owens BMJ, Bullers SJ, Linggi B, Buonocore S, et al. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat Med. 2017;23(5):579–89. This study shows that high expression of oncostatin M is strongly associated with failure of anti-TNF therapy.

Title: Novel Therapies and Treatment Strategies for Patients with Inflammatory Bowel Disease
Authors: Marjolijn Duijvestein, MD, PhD
Robert Battat, MD
Niels Vande Casteele, PharmD, PhD
Geert R. D’Haens, MD, PhD
William J. Sandborn, MD
Reena Khanna, MD
Vipul Jairath, MD, PhD
Brian G. Feagan, MD
Publication date: 01-03-2018
Publisher: Springer US
Published in: Current Treatment Options in Gastroenterology / Issue 1/2018
Print ISSN: 1092-8472
Electronic ISSN: 1534-309X
DOI: https://doi.org/10.1007/s11938-018-0175-1

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Novel Therapies and Treatment Strategies for Patients with Inflammatory Bowel Disease

Abstract

Purpose of review

Recent findings

Summary

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose of review

Recent findings

Summary

Please log in to get access to this content

Other articles of this Issue 1/2018

Expanding Role of Third Space Endoscopy in the Management of Esophageal Diseases

Update on Bowel Preparation for Colonoscopy

Updates on Women’s Health Issues in Patients with Inflammatory Bowel Disease

Management of Anemia in Patients with Inflammatory Bowel Disease (IBD)

Biosimilars in the Treatment of Inflammatory Bowel Disease: Supporting Evidence in 2017

Emerging Insights into the Esophageal Microbiome

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page