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Title: Translational research and efficacy of biologics in Crohn's disease: A cautionary tale
Authors: Van Den Bogaerde, J.
Trachter, R.
Auer, K.
Sorrentino, D.
Bassaganya-Riera, J.
Issue Date: 2014
Source: February 10, (2), 2014, p. 219-229
Pages: 219-229
Journal: Expert Review of Clinical Immunology
Abstract: In the last several years many biologic agents for Crohn's disease have been developed. Due to their unique molecular specificity biologics are de facto indicators of the ultimate significance of the molecule targeted by the biologic itself. Here, we have reviewed many clinical studies that have used biologics for Crohn's disease. Their results show that despite potentially sound theoretical mechanisms of action and some initially promising data, most biologics-with few notable exceptions - have failed. Pharmacologic, study design or patient-related issues might explain these findings in some studies. However in many cases clinical failure of biologics might highlight the complexity of in vivo events and the potential deficiencies of current experimental settings. Hence, these observations call for new and efficient ways of predicting drug efficacy in clinical trials based on bench research. Conceivably, computer-based pathogenetic models could be used to simulate and predict clinical studies results in vivo. 2014 Informa UK Ltd.
Keywords: biologic agentsclinical trials;computer-based disease models;Crohn's disease;Crohn's disease pathogenesis;monoclonal antibodies;translational research;clinical trial (topic);Crohn disease;drug efficacy;drug mechanism;drug research;drug targeting;human;immune response;in vivo study;nonhuman;review;study design;systematic review (topic);Th1 cell;Th17 cell;alicaforsen;apilimod;biological product/ct [Clinical Trial];biological product/pd [Pharmacology];briakinumab/ec [Endogenous Compound];doramapimod;fontolizumab;gamma interferon/ec [Endogenous Compound];interleukin 10/ec [Endogenous Compound];interleukin 11/ec [Endogenous Compound];interleukin 12/ec [Endogenous Compound];interleukin 12 antibody;interleukin 17/ec [Endogenous Compound];interleukin 23/ec [Endogenous Compound];interleukin 6/ec [Endogenous Compound];Janus kinase inhibitor/ec [Endogenous Compound];mitogen activated protein kinase inhibitor/ec [Endogenous Compound];natalizumab;recombinant interleukin 10;recombinant interleukin 11;secukinumab;semapimod;tocilizumab;tofacitinib;tumor necrosis factor alpha/ec [Endogenous Compound];ustekinumab;vedolizumab;vidofludimus
Type: Article
Appears in Collections:Sunshine Coast

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