Can We Predict the Efficacy of Anti-TNF-α Agents?

Loris Riccardo Lopetuso, Viviana Gerardi, Valerio Papa, Franco Scaldaferri, Gian Lodovico Rapaccini, Antonio Gasbarrini, Alfredo Papa, Loris Riccardo Lopetuso, Viviana Gerardi, Valerio Papa, Franco Scaldaferri, Gian Lodovico Rapaccini, Antonio Gasbarrini, Alfredo Papa

Abstract

The use of biologic agents, particularly anti-tumor necrosis factor (TNF)-α, has revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Several data on the efficacy of these agents in inducing and maintaining clinical remission have been accumulated over the past two decades: their use avoid the need for steroids therapy, promote mucosal healing, reduce hospitalizations and surgeries and therefore dramatically improve the quality of life of IBD patients. However, primary non-response to these agents or loss of response over time mainly due to immunogenicity or treatment-related side-effects are a frequent concern in IBD patients. Thus, the identification of predicting factors of efficacy is crucial to allow clinicians to efficiently use these therapies, avoiding them when they are ineffective and eventually shifting towards alternative biological therapies with the end goal of optimizing the cost-effectiveness ratio. In this review, we aim to identify the predictive factors of short- and long-term benefits of anti-TNF-α therapy in IBD patients. In particular, multiple patient-, disease- and treatment-related factors have been evaluated.

Keywords: Crohn’s disease; anti-TNF-α; biologics; inflammatory bowel disease; long-term efficacy; predictors; short-term efficacy; ulcerative colitis.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Bamias G., Corridoni D., Pizarro T.T., Cominelli F. New insights into the dichotomous role of innate cytokines in gut homeostasis and inflammation. Cytokine. 2012;59:451–459. doi: 10.1016/j.cyto.2012.06.014.
    1. Torres J., Mehandru S., Colombel J.F., Peyrin-Biroulet L. Crohn’s disease. Lancet. 2017;389:1741–1755. doi: 10.1016/S0140-6736(16)31711-1.
    1. Ungaro R., Mehandru S., Allen P.B., Peyrin-Biroulet L., Colombel J.F. Ulcerative colitis. Lancet. 2017;389:1756–1770. doi: 10.1016/S0140-6736(16)32126-2.
    1. Ha C., Ullman T.A., Siegel C.A., Kornbluth A. Patients enrolled in randomized controlled trials do not represent the inflammatory bowel disease patient population. Clin. Gastroenterol. Hepatol. 2012;10:1002–1007. doi: 10.1016/j.cgh.2012.02.004.
    1. Ben-Horin S., Kopylov U., Chowers Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun. Rev. 2014;13:24–30. doi: 10.1016/j.autrev.2013.06.002.
    1. Peyrin-Biroulet L., Reinisch W., Colombel J.F., Mantzaris G.J., Kornbluth A., Diamond R., Rutgeerts P., Tang L.K., Cornillie F.J., Sandborn W.J. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn’s disease in the SONIC trial. Gut. 2014;63:88–95. doi: 10.1136/gutjnl-2013-304984.
    1. Reinisch W., Colombel J.F., Sandborn W.J., Mantzaris G.J., Kornbluth A., Adedokun O.J., Miller M., Tang K.L., Rutgeerts P., Cornillie F. Factors associated with short- and long-term outcomes of therapy for Crohn’s disease. Clin. Gastroenterol. Hepatol. 2015;13:539–547. doi: 10.1016/j.cgh.2014.09.031.
    1. Babickova J., Tothova L., Lengyelova E., Bartonova A., Hodosy J., Gardlik R., Celec P. Sex differences in experimentally induced colitis in mice: A role for estrogens. Inflammation. 2015;38:1996–2006. doi: 10.1007/s10753-015-0180-7.
    1. Gonzalez-Lama Y., Fernandez-Blanco I., Lopez-SanRoman A., Taxonera C., Casis B., Tabernero S., Bermejo F., Martinez-Silva F., Mendoza J.L., Martinez-Montiel P., et al. Open-label infliximab therapy in ulcerative colitis: A multicenter survey of results and predictors of response. Hepato-Gastroenterology. 2008;55:1609–1614. doi: 10.1016/S1873-9954(07)70040-X.
    1. Nasuno M., Miyakawa M., Tanaka H., Motoya S. Short- and long-term outcomes of infliximab treatment for steroid-refractory ulcerative colitis and related prognostic factors: A single-center retrospective study. Digestion. 2017;95:67–71. doi: 10.1159/000452459.
    1. Zampeli E., Gizis M., Siakavellas S.I., Bamias G. Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis. World J. Gastrointest. Pathophysiol. 2014;5:293–303.
    1. Juillerat P., Sokol H., Froehlich F., Yajnik V., Beaugerie L., Lucci M., Burnand B., Macpherson A.J., Cosnes J., Korzenik J.R. Factors associated with durable response to infliximab in Crohn’s disease 5 years and beyond: A multicenter international cohort. Inflamm. Bowel Dis. 2015;21:60–70. doi: 10.1097/MIB.0000000000000225.
    1. Ferrante M., Vermeire S., Fidder H., Schnitzler F., Noman M., van Assche G., de Hertogh G., Hoffman I., D’Hoore A., van Steen K., et al. Long-term outcome after infliximab for refractory ulcerative colitis. J. Crohn’s Colitis. 2008;2:219–225. doi: 10.1016/j.crohns.2008.03.004.
    1. Bouguen G., Levesque B.G., Feagan B.G., Kavanaugh A., Peyrin-Biroulet L., Colombel J.F., Hanauer S.B., Sandborn W.J. Treat to target: A proposed new paradigm for the management of Crohn’s disease. Clin. Gastroenterol. Hepatol. 2015;13:1042–1050. doi: 10.1016/j.cgh.2013.09.006.
    1. Parsi M.A., Achkar J.P., Richardson S., Katz J., Hammel J.P., Lashner B.A., Brzezinski A. Predictors of response to infliximab in patients with Crohn’s disease. Gastroenterology. 2002;123:707–713. doi: 10.1053/gast.2002.35390.
    1. Arnott I.D., McNeill G., Satsangi J. An analysis of factors influencing short-term and sustained response to infliximab treatment for Crohn’s disease. Aliment. Pharmacol. Ther. 2003;17:1451–1457. doi: 10.1046/j.1365-2036.2003.01574.x.
    1. Vermeire S., Louis E., Carbonez A., van Assche G., Noman M., Belaiche J., de Vos M., van Gossum A., Pescatore P., Fiasse R., et al. Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn’s disease. Am. J. Gastroenterol. 2002;97:2357–2363. doi: 10.1111/j.1572-0241.2002.05991.x.
    1. Fefferman D.S., Lodhavia P.J., Alsahli M., Falchuk K.R., Peppercorn M.A., Shah S.A., Farrell R.J. Smoking and immunomodulators do not influence the response or duration of response to infliximab in Crohn’s disease. Inflamm. Bowel Dis. 2004;10:346–351. doi: 10.1097/00054725-200407000-00004.
    1. Orlando A., Colombo E., Kohn A., Biancone L., Rizzello F., Viscido A., Sostegni R., Benazzato L., Castiglione F., Papi C., et al. Infliximab in the treatment of Crohn’s disease: Predictors of response in an Italian multicentric open study. Dig. Liver Dis. 2005;37:577–583. doi: 10.1016/j.dld.2005.01.019.
    1. Reinisch W., Sandborn W.J., Hommes D.W., D’Haens G., Hanauer S., Schreiber S., Panaccione R., Fedorak R.N., Tighe M.B., Huang B., 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. doi: 10.1136/gut.2010.221127.
    1. Harper J.W., Sinanan M.N., Zisman T.L. Increased body mass index is associated with earlier time to loss of response to infliximab in patients with inflammatory bowel disease. Inflamm. Bowel Dis. 2013;19:2118–2124. doi: 10.1097/MIB.0b013e31829cf401.
    1. Assa A., Hartman C., Weiss B., Broide E., Rosenbach Y., Zevit N., Bujanover Y., Shamir R. Long-term outcome of tumor necrosis factor α antagonist’s treatment in pediatric Crohn’s disease. J. Crohn’s Colitis. 2013;7:369–376. doi: 10.1016/j.crohns.2012.03.006.
    1. Grover Z., Biron R., Carman N., Lewindon P. Predictors of response to infliximab in children with luminal Crohn’s disease. J. Crohn’s Colitis. 2014;8:739–746. doi: 10.1016/j.crohns.2013.12.017.
    1. Papamichael K., Vande Casteele N., Gils A., Tops S., Hauenstein S., Singh S., Princen F., van Assche G., Rutgeerts P., Vermeire S., et al. Long-term outcome of patients with Crohn’s disease who discontinued infliximab therapy upon clinical remission. Clin. Gastroenterol. Hepatol. 2015;13:1103–1110. doi: 10.1016/j.cgh.2014.11.026.
    1. Molander P., Farkkila M., Kemppainen H., Blomster T., Jussila A., Mustonen H., Sipponen T. Long-term outcome of inflammatory bowel disease patients with deep remission after discontinuation of TNFα-blocking agents. Scand. J. Gastroenterol. 2017;52:284–290. doi: 10.1080/00365521.2016.1250942.
    1. Jakobovits S.L., Jewell D.P., Travis S.P. Infliximab for the treatment of ulcerative colitis: Outcomes in Oxford from 2000 to 2006. Aliment. Pharmacol. Ther. 2007;25:1055–1060. doi: 10.1111/j.1365-2036.2007.03300.x.
    1. Sandborn W.J., Rutgeerts P., Feagan B.G., Reinisch W., Olson A., Johanns J., Lu J., Horgan K., Rachmilewitz D., Hanauer S.B., et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology. 2009;137:1250–1260. doi: 10.1053/j.gastro.2009.06.061.
    1. Schreiber S., Colombel J.F., Bloomfield R., Nikolaus S., Scholmerich J., Panes J., Sandborn W.J., Investigators P.R.S. Increased response and remission rates in short-duration Crohn’s disease with subcutaneous certolizumab pegol: An analysis of PRECiSE 2 randomized maintenance trial data. Am. J. Gastroenterol. 2010;105:1574–1582. doi: 10.1038/ajg.2010.78.
    1. Colombel J.F., Sandborn W.J., Rutgeerts P., Enns R., Hanauer S.B., Panaccione R., Schreiber S., Byczkowski D., Li J., Kent J.D., et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: The CHARM trial. Gastroenterology. 2007;132:52–65. doi: 10.1053/j.gastro.2006.11.041.
    1. Lionetti P., Bronzini F., Salvestrini C., Bascietto C., Canani R.B., de Angelis G.L., Guariso G., Martelossi S., Papadatou B., Barabino A. Response to infliximab is related to disease duration in paediatric Crohn’s disease. Aliment. Pharmacol. Ther. 2003;18:425–431. doi: 10.1046/j.1365-2036.2003.01672.x.
    1. Hyams J., Crandall W., Kugathasan S., Griffiths A., Olson A., Johanns J., Liu G., Travers S., Heuschkel R., Markowitz J., et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132:863–873. doi: 10.1053/j.gastro.2006.12.003.
    1. Ferrante M., Vermeire S., Katsanos K.H., Noman M., van Assche G., Schnitzler F., Arijs I., de Hertogh G., Hoffman I., Geboes J.K., et al. Predictors of early response to infliximab in patients with ulcerative colitis. Inflamm. Bowel Dis. 2007;13:123–128. doi: 10.1002/ibd.20054.
    1. Park S.H., Yang S.K., Hong S.M., Park S.K., Kim J.W., Lee H.J., Yang D.H., Jung K.W., Kim K.J., Ye B.D., et al. Severe disease activity and cytomegalovirus colitis are predictive of a nonresponse to infliximab in patients with ulcerative colitis. Dig. Dis. Sci. 2013;58:3592–3599. doi: 10.1007/s10620-013-2828-1.
    1. Jurgens M., Laubender R.P., Hartl F., Weidinger M., Seiderer J., Wagner J., Wetzke M., Beigel F., Pfennig S., Stallhofer J., et al. Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis. Am. J. Gastroenterol. 2010;105:1811–1819. doi: 10.1038/ajg.2010.95.
    1. Detrez I., Dreesen E., van Stappen T., de Vries A., Brouwers E., van Assche G., Vermeire S., Ferrante M., Gils A. Variability in golimumab exposure: A “real-life” observational study in active ulcerative colitis. J. Crohn’s Colitis. 2016;10:575–581. doi: 10.1093/ecco-jcc/jjv241.
    1. Moran G.W., Dubeau M.F., Kaplan G.G., Yang H., Seow C.H., Fedorak R.N., Dieleman L.A., Barkema H.W., Ghosh S., Panaccione R. Phenotypic features of Crohn’s disease associated with failure of medical treatment. Clin. Gastroenterol. Hepatol. 2014;12:434–442. doi: 10.1016/j.cgh.2013.08.026.
    1. Colombel J.F., Sandborn W.J., Allez M., Dupas J.L., Dewit O., D’Haens G., Bouhnik Y., Parker G., Pierre-Louis B., Hebuterne X. Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn’s disease. Clin. Gastroenterol. Hepatol. 2014;12:423–431. doi: 10.1016/j.cgh.2013.10.025.
    1. Ding N.S., Hart A., de Cruz P. Systematic review: Predicting and optimising response to anti-TNF therapy in Crohn’s disease—Algorithm for practical management. Aliment. Pharmacol. Ther. 2016;43:30–51. doi: 10.1111/apt.13445.
    1. Brandse J.F., van den Brink G.R., Wildenberg M.E., van der Kleij D., Rispens T., Jansen J.M., Mathot R.A., Ponsioen C.Y., Lowenberg M., D’Haens G.R. Loss of infliximab into feces is associated with lack of response to therapy in patients with severe ulcerative colitis. Gastroenterology. 2015;149:350–355. doi: 10.1053/j.gastro.2015.04.016.
    1. Lopetuso L.R., Petito V., Cufino V., Arena V., Stigliano E., Gerardi V., Gaetani E., Poscia A., Amato A., Cammarota G., et al. Locally injected infliximab ameliorates murine DSS colitis: Differences in serum and intestinal levels of drug between healthy and colitic mice. Dig. Liver Dis. 2013;45:1017–1021. doi: 10.1016/j.dld.2013.06.007.
    1. Silverberg M.S., Satsangi J., Ahmad T., Arnott I.D., Bernstein C.N., Brant S.R., Caprilli R., Colombel J.F., Gasche C., Geboes K., et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a working party of the 2005 Montreal World Congress of Gastroenterology. Can. J. Gastroenterol. 2005;19:5A–36A. doi: 10.1155/2005/269076.
    1. Kiss L.S., Szamosi T., Molnar T., Miheller P., Lakatos L., Vincze A., Palatka K., Barta Z., Gasztonyi B., Salamon A., et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn’s disease. Aliment. Pharmacol. Ther. 2011;34:911–922. doi: 10.1111/j.1365-2036.2011.04827.x.
    1. Lee K.M., Jeen Y.T., Cho J.Y., Lee C.K., Koo J.S., Park D.I., Im J.P., Park S.J., Kim Y.S., Kim T.O., et al. Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis: A Korean multicenter retrospective study. J. Gastroenterol. Hepatol. 2013;28:1829–1833. doi: 10.1111/jgh.12324.
    1. Louis E., Vermeire S., Rutgeerts P., de Vos M., van Gossum A., Pescatore P., Fiasse R., Pelckmans P., Reynaert H., D’Haens G., et al. Inflammatory Bowel Disease a positive response to infliximab in Crohn disease: Association with a higher systemic inflammation before treatment but not with-308 TNF gene polymorphism. Scand. J. Gastroenterol. 2002;37:818–824. doi: 10.1080/gas.37.7.818.824.
    1. Schreiber S., Rutgeerts P., Fedorak R.N., Khaliq-Kareemi M., Kamm M.A., Boivin M., Bernstein C.N., Staun M., Thomsen O.O., Innes A. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease. Gastroenterology. 2005;129:807–818. doi: 10.1053/j.gastro.2005.06.064.
    1. Jurgens M., Mahachie John J.M., Cleynen I., Schnitzler F., Fidder H., van Moerkercke W., Ballet V., Noman M., Hoffman I., van Assche G., et al. Levels of C-reactive protein are associated with response to infliximab therapy in patients with Crohn’s disease. Clin. Gastroenterol. Hepatol. 2011;9:421–427. doi: 10.1016/j.cgh.2011.02.008.
    1. Baert F., Glorieus E., Reenaers C., D’Haens G., Peeters H., Franchimont D., Dewit O., Caenepeel P., Louis E., van Assche G., et al. Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn’s patients. J. Crohn’s Colitis. 2013;7:154–160. doi: 10.1016/j.crohns.2012.03.018.
    1. Oussalah A., Evesque L., Laharie D., Roblin X., Boschetti G., Nancey S., Filippi J., Flourie B., Hebuterne X., Bigard M.A., et al. A multicenter experience with infliximab for ulcerative colitis: Outcomes and predictors of response, optimization, colectomy, and hospitalization. Am. J. Gastroenterol. 2010;105:2617–2625. doi: 10.1038/ajg.2010.345.
    1. Fasanmade A.A., Adedokun O.J., Olson A., Strauss R., Davis H.M. 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. doi: 10.5414/CPP48297.
    1. Esters N., Vermeire S., Joossens S., Noman M., Louis E., Belaiche J., de Vos M., van Gossum A., Pescatore P., Fiasse R., et al. Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn’s disease. Am. J. Gastroenterol. 2002;97:1458–1462. doi: 10.1111/j.1572-0241.2002.05689.x.
    1. Taylor K.D., Plevy S.E., Yang H., Landers C.J., Barry M.J., Rotter J.I., Targan S.R. ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn’s disease. Gastroenterology. 2001;120:1347–1355. doi: 10.1053/gast.2001.23966.
    1. Taxonera C., Estelles J., Fernandez-Blanco I., Merino O., Marin-Jimenez I., Barreiro-de Acosta M., Saro C., Garcia-Sanchez V., Gento E., Bastida G., et al. Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab. Aliment. Pharmacol. Ther. 2011;33:340–348. doi: 10.1111/j.1365-2036.2010.04531.x.
    1. Garcia-Bosch O., Gisbert J.P., Canas-Ventura A., Merino O., Cabriada J.L., Garcia-Sanchez V., Gutierrez A., Nos P., Penalva M., Hinojosa J., et al. Observational study on the efficacy of adalimumab for the treatment of ulcerative colitis and predictors of outcome. J.Crohn’s Colitis. 2013;7:717–722. doi: 10.1016/j.crohns.2012.10.004.
    1. McDermott E., Murphy S., Keegan D., O’Donoghue D., Mulcahy H., Doherty G. Efficacy of adalimumab as a long term maintenance therapy in ulcerative colitis. J. Crohn’s Colitis. 2013;7:150–153. doi: 10.1016/j.crohns.2012.03.016.
    1. Armuzzi A., Biancone L., Daperno M., Coli A., Pugliese D., Annese V., Aratari A., Ardizzone S., Balestrieri P., Bossa F., et al. Adalimumab in active ulcerative colitis: A “real-life” observational study. Dig. Liver Dis. 2013;45:738–743. doi: 10.1016/j.dld.2013.03.018.
    1. Neurath M.F., Travis S.P. Mucosal healing in inflammatory bowel diseases: A systematic review. Gut. 2012;61:1619–1635. doi: 10.1136/gutjnl-2012-302830.
    1. Colombel J.F., Rutgeerts P., Reinisch W., Esser D., Wang Y., Lang Y., Marano C.W., Strauss R., Oddens B.J., Feagan B.G., et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141:1194–1201. doi: 10.1053/j.gastro.2011.06.054.
    1. Gustavsson A., Jarnerot G., Hertervig E., Friis-Liby I., Blomquist L., Karlen P., Granno C., Vilien M., Strom M., Verbaan H., et al. Clinical trial: Colectomy after rescue therapy in ulcerative colitis—3-Year follow-up of the Swedish-Danish controlled infliximab study. Aliment. Pharmacol. Ther. 2010;32:984–989. doi: 10.1111/j.1365-2036.2010.04435.x.
    1. Schnitzler F., Fidder H., Ferrante M., Noman M., Arijs I., van Assche G., Hoffman I., van Steen K., Vermeire S., Rutgeerts P. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm. Bowel Dis. 2009;15:1295–1301. doi: 10.1002/ibd.20927.
    1. Baert F., Moortgat L., van Assche G., Caenepeel P., Vergauwe P., de Vos M., Stokkers P., Hommes D., Rutgeerts P., Vermeire S., et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–468. doi: 10.1053/j.gastro.2009.09.056.
    1. Af Bjorkesten C.G., Nieminen U., Turunen U., Arkkila P.E., Sipponen T., Farkkila M.A. Endoscopic monitoring of infliximab therapy in Crohn’s disease. Inflamm. Bowel Dis. 2011;17:947–953. doi: 10.1002/ibd.21439.
    1. Af Bjorkesten C.G., Nieminen U., Sipponen T., Turunen U., Arkkila P., Farkkila M. Mucosal healing at 3 months predicts long-term endoscopic remission in anti-TNF-treated luminal Crohn’s disease. Scand. J. Gastroenterol. 2013;48:543–551. doi: 10.3109/00365521.2013.772230.
    1. Vande Casteele N., Gils A., Singh S., Ohrmund L., Hauenstein S., Rutgeerts P., Vermeire S. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am. J. Gastroenterol. 2013;108:962–971. doi: 10.1038/ajg.2013.12.
    1. Morita Y., Bamba S., Takahashi K., Imaeda H., Nishida A., Inatomi O., Sasaki M., Tsujikawa T., Sugimoto M., Andoh A. Prediction of clinical and endoscopic responses to anti-tumor necrosis factor-α antibodies in ulcerative colitis. Scand. J. Gastroenterol. 2016;51:934–941. doi: 10.3109/00365521.2016.1144781.
    1. Baert F., Vande Casteele N., Tops S., Noman M., van Assche G., Rutgeerts P., Gils A., Vermeire S., Ferrante M. Prior response to infliximab and early serum drug concentrations predict effects of adalimumab in ulcerative colitis. Aliment. Pharmacol. Ther. 2014;40:1324–1332. doi: 10.1111/apt.12968.
    1. Sandborn W.J., Feagan B.G., Marano C., Zhang H., Strauss R., Johanns J., Adedokun O.J., Guzzo C., Colombel J.F., Reinisch W., et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:85–95. doi: 10.1053/j.gastro.2013.05.048.
    1. Sandborn W.J., Feagan B.G., Marano C., Zhang H., Strauss R., Johanns J., Adedokun O.J., Guzzo C., Colombel J.F., Reinisch W., et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96–109. doi: 10.1053/j.gastro.2013.06.010.
    1. Adedokun O.J., Xu Z., Marano C.W., Strauss R., Zhang H., Johanns J., Zhou H., Davis H.M., Reinisch W., Feagan B.G., et al. Pharmacokinetics and exposure-response relationship of golimumab in patients with moderately-to-severely active ulcerative colitis: Results from phase 2/3 PURSUIT induction and maintenance studies. J. Crohn’s Colitis. 2017;11:35–46. doi: 10.1093/ecco-jcc/jjw133.
    1. Drabik A., Sturm A., Blomacher M., Helwig U. Early monitoring of response (MORE) to golimumab therapy based on fecal calprotectin and trough serum levels in patients with ulcerative colitis: A multicenter prospective study. JMIR Res. Protoc. 2016;5:e124. doi: 10.2196/resprot.5791.
    1. Vande Casteele N., Khanna R., Levesque B.G., Stitt L., Zou G.Y., Singh S., Lockton S., Hauenstein S., Ohrmund L., Greenberg G.R., et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn’s disease. Gut. 2015;64:1539–1545. doi: 10.1136/gutjnl-2014-307883.
    1. Bortlik M., Duricova D., Malickova K., Machkova N., Bouzkova E., Hrdlicka L., Komarek A., Lukas M. Infliximab trough levels may predict sustained response to infliximab in patients with Crohn’s disease. J. Crohn’s Colitis. 2013;7:736–743. doi: 10.1016/j.crohns.2012.10.019.
    1. Karmiris K., Paintaud G., Noman M., Magdelaine-Beuzelin C., Ferrante M., Degenne D., Claes K., Coopman T., van Schuerbeek N., van Assche G., et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn’s disease. Gastroenterology. 2009;137:1628–1640. doi: 10.1053/j.gastro.2009.07.062.
    1. Mazor Y., Almog R., Kopylov U., Ben Hur D., Blatt A., Dahan A., Waterman M., Ben-Horin S., Chowers Y. Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn’s disease. Aliment. Pharmacol. Ther. 2014;40:620–628. doi: 10.1111/apt.12869.
    1. Roblin X., Marotte H., Rinaudo M., del Tedesco E., Moreau A., Phelip J.M., Genin C., Peyrin-Biroulet L., Paul S. Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases. Clin. Gastroenterol. Hepatol. 2014;12:80–84. doi: 10.1016/j.cgh.2013.07.010.
    1. Seow C.H., Newman A., Irwin S.P., Steinhart A.H., Silverberg M.S., Greenberg G.R. Trough serum infliximab: A predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59:49–54. doi: 10.1136/gut.2009.183095.
    1. Steenholdt C., Bendtzen K., Brynskov J., Thomsen O.O., Ainsworth M.A. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn’s disease. Scand. J. Gastroenterol. 2011;46:310–318. doi: 10.3109/00365521.2010.536254.
    1. Ben-Horin S., Yavzori M., Katz L., Kopylov U., Picard O., Fudim E., Coscas D., Bar-Meir S., Goldstein I., Chowers Y. The immunogenic part of infliximab is the F(ab’)2, but measuring antibodies to the intact infliximab molecule is more clinically useful. Gut. 2011;60:41–48. doi: 10.1136/gut.2009.201533.
    1. Hanauer S.B., Wagner C.L., Bala M., Mayer L., Travers S., Diamond R.H., Olson A., Bao W., Rutgeerts P. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin. Gastroenterol. Hepatol. 2004;2:542–553. doi: 10.1016/S1542-3565(04)00238-1.
    1. Toedter G., Li K., Marano C., Ma K., Sague S., Huang C.C., Song X.Y., Rutgeerts P., Baribaud F. Gene expression profiling and response signatures associated with differential responses to infliximab treatment in ulcerative colitis. Am. J. Gastroenterol. 2011;106:1272–1280. doi: 10.1038/ajg.2011.83.
    1. Arijs I., Li K., Toedter G., Quintens R., van Lommel L., van Steen K., Leemans P., de Hertogh G., Lemaire K., Ferrante M., et al. Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis. Gut. 2009;58:1612–1619. doi: 10.1136/gut.2009.178665.
    1. Li Z., Arijs I., de Hertogh G., Vermeire S., Noman M., Bullens D., Coorevits L., Sagaert X., Schuit F., Rutgeerts P., et al. Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab. Inflamm. Bowel Dis. 2010;16:1299–1310. doi: 10.1002/ibd.21229.
    1. Olsen T., Goll R., Cui G., Christiansen I., Florholmen J. TNF-α gene expression in colorectal mucosa as a predictor of remission after induction therapy with infliximab in ulcerative colitis. Cytokine. 2009;46:222–227. doi: 10.1016/j.cyto.2009.02.001.
    1. Rismo R., Olsen T., Cui G., Christiansen I., Florholmen J., Goll R. Mucosal cytokine gene expression profiles as biomarkers of response to infliximab in ulcerative colitis. Scand. J. Gastroenterol. 2012;47:538–547. doi: 10.3109/00365521.2012.667146.
    1. Urcelay E., Mendoza J.L., Martinez A., Fernandez L., Taxonera C., Diaz-Rubio M., de la Concha E.G. IBD5 polymorphisms in inflammatory bowel disease: Association with response to infliximab. World J. Gastroenterol. WJG. 2005;11:1187–1192. doi: 10.3748/wjg.v11.i8.1187.
    1. Louis E., el Ghoul Z., Vermeire S., Dall’Ozzo S., Rutgeerts P., Paintaud G., Belaiche J., de Vos M., van Gossum A., Colombel J.F., et al. Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn’s disease. Aliment. Pharmacol. Ther. 2004;19:511–519. doi: 10.1111/j.1365-2036.2004.01871.x.
    1. Pierik M., Vermeire S., Steen K.V., Joossens S., Claessens G., Vlietinck R., Rutgeerts P. Tumour necrosis factor-α receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab. Aliment. Pharmacol. Ther. 2004;20:303–310. doi: 10.1111/j.1365-2036.2004.01946.x.
    1. Mascheretti S., Hampe J., Kuhbacher T., Herfarth H., Krawczak M., Folsch U.R., Schreiber S. Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with chronic active Crohn’s disease treated with infliximab. Pharmacogenom. J. 2002;2:127–136. doi: 10.1038/sj.tpj.6500091.
    1. Mascheretti S., Hampe J., Croucher P.J., Nikolaus S., Andus T., Schubert S., Olson A., Bao W., Folsch U.R., Schreiber S. Response to infliximab treatment in Crohn’s disease is not associated with mutations in the CARD15 (NOD2) gene: An analysis in 534 patients from two multicenter, prospective GCP-level trials. Pharmacogenetics. 2002;12:509–515. doi: 10.1097/00008571-200210000-00002.
    1. Vermeire S., Louis E., Rutgeerts P., de Vos M., van Gossum A., Belaiche J., Pescatore P., Fiasse R., Pelckmans P., Vlietinck R., et al. NOD2/CARD15 does not influence response to infliximab in Crohn’s disease. Gastroenterology. 2002;123:106–111. doi: 10.1053/gast.2002.34172.
    1. Hlavaty T., Pierik M., Henckaerts L., Ferrante M., Joossens S., van Schuerbeek N., Noman M., Rutgeerts P., Vermeire S. Polymorphisms in apoptosis genes predict response to infliximab therapy in luminal and fistulizing Crohn’s disease. Aliment. Pharmacol. Ther. 2005;22:613–626. doi: 10.1111/j.1365-2036.2005.02635.x.
    1. Hlavaty T., Ferrante M., Henckaerts L., Pierik M., Rutgeerts P., Vermeire S. Predictive model for the outcome of infliximab therapy in Crohn’s disease based on apoptotic pharmacogenetic index and clinical predictors. Inflamm. Bowel Dis. 2007;13:372–379. doi: 10.1002/ibd.20024.

Source: PubMed

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