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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 4/2017

01-04-2017 | Paradigm Shifts in Perspective

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Authors: M. Anthony Sofia, David T. Rubin

Published in: Digestive Diseases and Sciences | Issue 4/2017

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Abstract

The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn’s disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.
Literature
1.
Ritchie J, Powell-Tuck T, Lennard-Jones JE. Clinical outcome of the first ten years of ulcerative colitis and proctitis. Lancet. 1978;311:1140–1143.CrossRef
2.
Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA. 1975;72:3666–3670.PubMedPubMedCentralCrossRef
3.
Beutler B, Greenwald D, Hulmes JD, et al. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature. 1985;316:552–554.PubMedCrossRef
4.
Simpson SJ, Hollander GA, Mizoguchi E, et al. Expression of pro-inflammatory cytokines by TCR alpha beta + and TCR gamma delta + T cells in an experimental model of colitis. Eur J Immunol. 1997;27:17–25.PubMedCrossRef
5.
Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–497.PubMedCrossRef
6.
Shawler DL, Bartholomew RM, Smith LM, Dillman RO. Human immune response to multiple injections of murine monoclonal IgG. J Immunol (Baltimore, MD: 1950). 1985;135:1530–1535.
7.
Boulianne GL, Hozumi N, Shulman MJ. Production of functional chimaeric mouse/human antibody. Nature. 1984;312:643–646.PubMedCrossRef
8.
Knight DM, Trinh H, Le J, et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol. 1993;30:1443–1453.PubMedCrossRef
9.
Siegel SA, Shealy DJ, Nakada MT, et al. The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo. Cytokine. 1995;7:15–25.PubMedCrossRef
10.
Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J. Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine. 1995;7:251–259.PubMedCrossRef
11.
van Dullemen HM, van Deventer SJ, Hommes DW, et al. Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology. 1995;109:129–135.PubMedCrossRef
12.
Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med. 1997;337:1029–1035.PubMedCrossRef
13.
Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340:1398–1405.PubMedCrossRef
14.
Sands BE, Tremaine WJ, Sandborn WJ, et al. Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Inflamm Bowel Dis. 2001;7:83–88.PubMedCrossRef
15.
Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.PubMedCrossRef
16.
Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549.PubMedCrossRef
17.
Rutgeerts P, D’Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology. 1999;117:761–769.PubMedCrossRef
18.
19.
Kornbluth A. Infliximab approved for use in Crohn’s disease: a report on the FDA GI Advisory Committee conference. Inflamm Bowel Dis. 1998;4:328–329.PubMed
20.
Fidder H, Schnitzler F, Ferrante M, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut. 2009;58:501–508.PubMedCrossRef
21.
Caspersen S, Elkjaer M, Riis L, et al. Infliximab for inflammatory bowel disease in Denmark 1999–2005: clinical outcome and follow-up evaluation of malignancy and mortality. Clin Gastroenterol Hepatol. 2008;6:1212–1217. (quiz 1176).PubMedCrossRef
22.
Lichtenstein GR, Rutgeerts P, Sandborn WJ, et al. A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease. Am J Gastroenterol. 2012;107:1051–1063.PubMedPubMedCentralCrossRef
23.
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT registry. Am J Gastroenterol. 2012;107:1409–1422.PubMedPubMedCentralCrossRef
24.
Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med. 2003;348:601–608.PubMedCrossRef
25.
Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–1395.PubMedCrossRef
26.
Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146:392.e393–400.e393.CrossRef
27.
Ben-Horin S, Waterman M, Kopylov U, et al. Addition of an immunomodulator to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11:444–447.PubMedCrossRef
28.
Rutgeerts P, Feagan BG, Lichtenstein GR, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease. Gastroenterology. 2004;126:402–413.PubMedCrossRef
29.
Magro F, Rodrigues-Pinto E, Santos-Antunes J, et al. High C-reactive protein in Crohn’s disease patients predicts nonresponse to infliximab treatment. J Crohns Colitis. 2014;8:129–136.PubMedCrossRef
30.
Brandse JF, Mathot RA, van der Kleij D, et al. Pharmacokinetic features and presence of antidrug antibodies associate with response to infliximab induction therapy in patients with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol. 2016;14:251.e252–258.e252.CrossRef
31.
Brandse JF, van den Brink GR, Wildenberg ME, et al. Loss of infliximab into feces is associated with lack of response to therapy in patients with severe ulcerative colitis. Gastroenterology. 2015;149:350.e352–355.e352.
32.
Atreya R, Neumann H, Neufert C, et al. In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn’s disease. Nat Med. 2014;20:313–318.PubMedPubMedCentralCrossRef
33.
Yarur AJ, Jain A, Sussman DA, et al. The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study. Gut. 2016;65:249–255.PubMedCrossRef
34.
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.PubMedCrossRef
35.
Gibson DJ, Heetun ZS, Redmond CE, et al. An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis. Clin Gastroenterol Hepatol. 2015;13:330.e331–335.e331.CrossRef
36.
Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148:1320.e1323–1329.e1323.CrossRef
37.
Froslie KF, Jahnsen J, Moum BA, Vatn MH. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412–422.PubMedCrossRef
38.
Meucci G, Fasoli R, Saibeni S, et al. Prognostic significance of endoscopic remission in patients with active ulcerative colitis treated with oral and topical mesalazine: a prospective, multicenter study. Inflamm Bowel Dis. 2012;18:1006–1010.PubMedCrossRef
39.
Hindryckx P, Baert F, Hart A, et al. Clinical trials in ulcerative colitis: a historical perspective. J Crohns Colitis. 2015;9:580–588.PubMedCrossRef
40.
Hanauer SB. The ethics of phase I trials of biologic agents. Nat Clin Pract Gastroenterol Hepatol. 2008;5:533.PubMedCrossRef
41.
Sandborn WJ. Preventing antibodies to infliximab in patients with Crohn’s disease: optimize not immunize. Gastroenterology. 2003;124:1140–1145.PubMedCrossRef
42.
Rubin DT, Becker S, Siegler M. Ethical considerations for clinical trials in inflammatory bowel disease. Gastroenterol Hepatol. 2014;10:37–41.
43.
Winter G, Griffiths AD, Hawkins RE, Hoogenboom HR. Making antibodies by phage display technology. Annu Rev Immunol. 1994;12:433–455.PubMedCrossRef
44.
Afif W, Leighton JA, Hanauer SB, et al. Open-label study of adalimumab in patients with ulcerative colitis including those with prior loss of response or intolerance to infliximab. Inflamm Bowel Dis. 2009;15:1302–1307.PubMedCrossRef
45.
Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60:780–787.PubMedCrossRef
46.
Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology.. 2012;142:257.e251-253–265.e251-253.CrossRef
47.
Sandborn WJ, Hanauer S, Loftus EV Jr, et al. An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn’s disease. Am J Gastroenterol. 2004;99:1984–1989.PubMedCrossRef
48.
Papadakis KA, Shaye OA, Vasiliauskas EA, et al. Safety and efficacy of adalimumab (D2E7) in Crohn’s disease patients with an attenuated response to infliximab. Am J Gastroenterol. 2005;100:75–79.PubMedCrossRef
49.
Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130:323–333. (quiz 591).PubMedCrossRef
50.
Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132:52–65.PubMedCrossRef
51.
Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007;56:1232–1239.PubMedPubMedCentralCrossRef
52.
Baert F, Kondragunta V, Lockton S, et al. Antibodies to adalimumab are associated with future inflammation in Crohn’s patients receiving maintenance adalimumab therapy: a post hoc analysis of the Karmiris trial. Gut. 2016;65:1126–1131.PubMedCrossRef
53.
Ong DE, Kamm MA, Hartono JL, Lust M. Addition of thiopurines can recapture response in patients with Crohn’s disease who have lost response to anti-tumor necrosis factor monotherapy. J Gastroenterol Hepatol. 2013;28:1595–1599.PubMed
54.
Baert F, Vande Casteele N, Tops S, et al. Prior response to infliximab and early serum drug concentrations predict effects of adalimumab in ulcerative colitis. Aliment Pharmacol Ther. 2014;40:1324–1332.PubMedCrossRef
55.
Frederiksen MT, Ainsworth MA, Brynskov J, Thomsen OO, Bendtzen K, Steenholdt C. Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD. Inflamm Bowel Dis. 2014;20:1714–1721.PubMedCrossRef
56.
Ananthakrishnan AN, Cagan A, Cai T, et al. Comparative Effectiveness of Infliximab and Adalimumab in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2016;22:880–885.PubMedCrossRef
57.
Chapman AP. PEGylated antibodies and antibody fragments for improved therapy: a review. Adv Drug Deliv Rev. 2002;54:531–545.PubMedCrossRef
58.
Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature. 1986;321:522–525.PubMedCrossRef
59.
60.
Schreiber S, Rutgeerts P, Fedorak RN, et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease. Gastroenterology. 2005;129:807–818.PubMedCrossRef
61.
Sandborn WJ, Schreiber S, Feagan BG, et al. Certolizumab pegol for active Crohn’s disease: a placebo-controlled, randomized trial. Clin Gastroenterol Hepatol. 2011;9:670.e673–678.e673.
62.
Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007;357:228–238.PubMedCrossRef
63.
Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007;357:239–250.PubMedCrossRef
64.
Rutgeerts P, Schreiber S, Feagan B, Keininger DL, O’Neil L, Fedorak RN. Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFα, improves health-related quality of life in patients with moderate to severe Crohn’s disease. Int J Colorectal Dis. 2008;23:289–296.PubMedCrossRef
65.
Feagan BG, Reilly MC, Gerlier L, Brabant Y, Brown M, Schreiber S. Clinical trial: the effects of certolizumab pegol therapy on work productivity in patients with moderate-to-severe Crohn’s disease in the PRECiSE 2 study. Aliment Pharmacol Ther. 2010;31:1276–1285.PubMedCrossRef
66.
Lang L. FDA approves Cimzia to treat Crohn’s disease. Gastroenterology. 2008;134:1819.PubMed
67.
Nesbitt A, Fossati G, Bergin M, et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflamm Bowel Dis. 2007;13:1323–1332.PubMedCrossRef
68.
Casteele NV, Stitt L, Spearman M, et al. Sa1937 exposure-response relationship for certolizumab pegol during the induction phase in patients. Gastroenterology. 2016;150:S409.
69.
Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate to severe ulcerative colitis. Gastroenterology. 2013.
70.
Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2013.
71.
Gordon FH, Lai CW, Hamilton MI, et al. A randomized placebo-controlled trial of a humanized monoclonal antibody to α4 integrin in active Crohn’s disease. Gastroenterology. 2001;121:268–274.PubMedCrossRef
72.
Ghosh S, Goldin E, Gordon FH, et al. Natalizumab for active Crohn’s disease. N Engl J Med. 2003;348:24–32.PubMedCrossRef
73.
Sandborn WJ, Colombel JF, Enns R, et al. Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2005;353:1912–1925.PubMedCrossRef
74.
Feagan BG, Greenberg GR, Wild G, et al. Treatment of active Crohn’s disease with MLN0002, a humanized antibody to the α4β7 integrin. Clin Gastroenterol Hepatol. 2008;6:1370–1377.PubMedCrossRef
75.
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.PubMedCrossRef
76.
Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369:711–721.PubMedCrossRef
77.
Sandborn WJ, Feagan BG, Fedorak RN, et al. 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.PubMedCrossRef
78.
Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med. 2012;367:1519–1528.PubMedCrossRef
79.
US Food and Drug Administration CfDEaR. Biologics License Application Approval: Stelara (ustekinumab). 2016.
80.
Hooks MA, Wade CS, Millikan WJ Jr. Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation. Pharmacotherapy. 1991;11:26–37.PubMed
81.
Millis JM, McDiarmid SV, Hiatt JR, et al. Randomized prospective trial of OKT3 for early prophylaxis of rejection after liver transplantation. Transplantation. 1989;47:82–88.PubMedCrossRef
82.
Lin CC, Chuang FR, Lee CH, et al. The renal-sparing efficacy of basiliximab in adult living donor liver transplantation. Liver Transpl. 2005;11:1258–1264.PubMedCrossRef
83.
Penninga L, Wettergren A, Wilson CH, Chan AW, Steinbruchel DA, Gluud C. Antibody induction versus corticosteroid induction for liver transplant recipients. Cochrane Database Syst Rev. 2014:Cd010252.
84.
Kovarik JM, Nashan B, Neuhaus P, et al. A population pharmacokinetic screen to identify demographic-clinical covariates of basiliximab in liver transplantation. Clin Pharmacol Ther. 2001;69:201–209.PubMedCrossRef
85.
Goralczyk AD, Hauke N, Bari N, Tsui TY, Lorf T, Obed A. Interleukin 2 receptor antagonists for liver transplant recipients: a systematic review and meta-analysis of controlled studies. Hepatology. 2011;54:541–554.PubMedCrossRef
86.
Crins ND, Rover C, Goralczyk AD, Friede T. Interleukin-2 receptor antagonists for pediatric liver transplant recipients: a systematic review and meta-analysis of controlled studies. Pediatr Transplant. 2014;18:839–850.PubMedCrossRef
87.
Rutgeerts PJ, Fedorak RN, Hommes DW, et al. A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis. Gut. 2013;62:1122–1130.PubMedCrossRef
88.
Vermeire S, O’Byrne S, Keir M, et al. Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet. 2014;384:309–318.PubMedCrossRef
89.
Gao Q, Meijer MJ, Kubben FJ, et al. Expression of matrix metalloproteinases-2 and -9 in intestinal tissue of patients with inflammatory bowel diseases. Dig Liver Dis. 2005;37:584–592.PubMedCrossRef
90.
Annahazi A, Molnar T, Farkas K, et al. Fecal MMP-9: a new noninvasive differential diagnostic and activity marker in ulcerative colitis. Inflamm Bowel Dis. 2013;19:316–320.PubMedCrossRef
91.
Chingcuanco F, Segal JB, Kim SC, Alexander GC. Bioequivalence of Biosimilar tumor necrosis factor-alpha inhibitors compared with their reference biologics: a systematic review. Ann Intern Med. 2016.
92.
Smits LJ, Derikx LA, de Jong DJ, et al. Clinical outcomes following a switch from Remicade® to the biosimilar CT-P13 in inflammatory bowel disease patients: a prospective observational cohort study. J Crohns Colitis. 2016.
93.
Kolar D, Brotlik M, Hruba V, et al. Switching of patients with inflammatory bowel disease from original infliximab (Remicade®) to biosimilar infliximab (Remsima™) is effective and safe. In: European Crohn’s and Colitis Organisation, Amsterdam, Netherlands; 2016.
94.
Bettey L, Underhill C, Callaghan J, Rush M, Ahmed I, Cummings, F. Outcomes of a managed switching programme changing IBD patients established on originator infliximab to biosimilar infliximab. In: European Crohn’s and Colitis Organisation, Amsterdam, Netherlands; 2016.
95.
Gecse KB, Lovasz BD, Farkas K, et al. Efficacy and safety of the biosimilar infliximab CT-P13 treatment in inflammatory bowel diseases: a prospective, multicentre, nationwide cohort. J Crohns Colitis. 2016;10:133–140.PubMedCrossRef
96.
Farkas K, Rutka M, Golovics PA, et al. Efficacy of infliximab biosimilar CT-P13 induction therapy on mucosal healing in ulcerative colitis. J Crohns Colitis. 2016.
97.
Sieczkowska J, Jarzebicka D, Banaszkiewicz A, et al. Switching between infliximab originator and biosimilar in paediatric patients with inflammatory bowel disease. Preliminary observations. J Crohns Colitis. 2016;10:127–132.PubMedCrossRef
98.
Ben-Horin S, Yavzori M, Benhar I, et al. Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima. Gut. 2016;65:1132–1138.PubMedCrossRef
99.
US Food and Drug Administration AAC. FDA Briefing Document: ABP 501, a Proposed Biosimilar to Humira (adalimumab). 2016.
100.
US Food and Drug Administration CfDEaR. Approval Package: Amjetiva (adalimumab-atto). Application Number 761024Orig1s000. 2016.
101.
Ananthakrishnan AN. Clostridium difficile infection: epidemiology, risk factors and management. Nat Rev Gastroenterol Hepatol. 2011;8:17–26.PubMedCrossRef
102.
Qiu H, Cassan R, Johnstone D, et al. Novel Clostridium difficile anti-toxin (TcdA and TcdB) humanized monoclonal antibodies demonstrate in vitro neutralization across a broad spectrum of clinical strains and in vivo potency in a hamster spore challenge model. PLoS ONE. 2016;11:e0157970.PubMedPubMedCentralCrossRef
103.
Koon HW, Shih DQ, Hing TC, et al. Human monoclonal antibodies against Clostridium difficile toxins A and B inhibit inflammatory and histologic responses to the toxins in human colon and peripheral blood monocytes. Antimicrob Agents Chemother. 2013;57:3214–3223.PubMedPubMedCentralCrossRef
104.
Yang Z, Ramsey J, Hamza T, et al. Mechanisms of protection against Clostridium difficile infection by the monoclonal antitoxin antibodies actoxumab and bezlotoxumab. Infect Immun. 2015;83:822–831.PubMedPubMedCentralCrossRef
105.
Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010;362:197–205.PubMedCrossRef
106.
US Food and Drug Administration ADAC. FDA Briefing Document: Bezlotoxumab Injection. 2016.
107.
Liaskou E, Karikoski M, Reynolds GM, et al. Regulation of mucosal addressin cell adhesion molecule 1 expression in human and mice by vascular adhesion protein 1 amine oxidase activity. Hepatology. 2011;53:661–672.PubMedPubMedCentralCrossRef
108.
Grant AJ, Lalor PF, Hubscher SG, Briskin M, Adams DH. MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease). Hepatology. 2001;33:1065–1072.PubMedCrossRef
109.
Halilbasic E, Fuchs C, Hofer H, Paumgartner G, Trauner M. Therapy of primary sclerosing cholangitis-today and tomorrow. Dig Dis. 2015;33:149–163.PubMedCrossRef
110.
111.
Stein ML, Collins MH, Villanueva JM, et al. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006;118:1312–1319.PubMedCrossRef
112.
Assa’ad AH, Gupta SK, Collins MH, et al. An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology. 2011;141:1593–1604.PubMedCrossRef
113.
Straumann A, Conus S, Grzonka P, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59:21–30.PubMedCrossRef
114.
van der Valk ME, Mangen MJ, Leenders M, et al. Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFalpha therapy: results from the COIN study. Gut. 2014;63:72–79.PubMedCrossRef
115.
Gleason PP, Alexander GC, Starner CI, et al. Health plan utilization and costs of specialty drugs within 4 chronic conditions. J Manag Care Pharm (JMCP). 2013;19:542–548.CrossRef
116.
Park KT, Sin A, Wu M, Bass D, Bhattacharya J. Utilization trends of anti-TNF agents and health outcomes in adults and children with inflammatory bowel diseases: a single-center experience. Inflamm Bowel Dis. 2014;20:1242–1249.PubMedPubMedCentralCrossRef
117.
Yokomizo L, Limketkai B, Park KT. Cost-effectiveness of adalimumab, infliximab or vedolizumab as first-line biological therapy in moderate-to-severe ulcerative colitis. BMJ Open Gastroenterol. 2016;3:e000093.PubMedPubMedCentralCrossRef
118.
Steenholdt C, Brynskov J, Thomsen OO, et al. Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014;63:919–927.PubMedCrossRef
119.
Roblin X, Attar A, Lamure M, et al. Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn’s disease patients who lose response to infliximab. J Mark Access Health Policy. 2015;3.
120.
Ananthakrishnan AN, Korzenik JR, Hur C. Can mucosal healing be a cost-effective endpoint for biologic therapy in Crohn’s disease? A decision analysis. Inflamm Bowel Dis. 2013;19:37–44.PubMedCrossRef
Metadata
Title
The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions
Authors
M. Anthony Sofia
David T. Rubin
Publication date
01-04-2017
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 4/2017
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-017-4479-0

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At a glance: The STEP trials

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A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

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Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

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

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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