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      Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

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          Abstract

          Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

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          Most cited references143

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          The global burden of IBD: from 2015 to 2025.

          Over 1 million residents in the USA and 2.5 million in Europe are estimated to have IBD, with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients. The majority of patients are diagnosed early in life and the incidence continues to rise; therefore, the effect of IBD on health-care systems will rise exponentially. Moreover, IBD has emerged in newly industrialized countries in Asia, South America and Middle East and has evolved into a global disease with rising prevalence in every continent. Understanding the worldwide epidemiological patterns of IBD will prepare us to manage the burden of IBD over time. The goal of this article is to establish the current epidemiology of IBD in the Western world, contrast it with the increase in IBD in newly industrialized countries and forecast the global effects of IBD in 2025.
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            Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

            Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy.
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              Vedolizumab as induction and maintenance therapy for ulcerative colitis.

              Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis. We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P 1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups. Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                19 February 2021
                February 2021
                : 10
                : 4
                : 853
                Affiliations
                [1 ]Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; gpp.privitera94@ 123456gmail.com (G.P.); gianludovico.rapaccini@ 123456policlinicogemelli.it (G.L.R.); antonio.gasbarrini@ 123456policlinicogemelli.it (A.G.); alessandro.armuzzi@ 123456policlinicogemelli.it (A.A.)
                [2 ]CEMAD—IBD UNIT—Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; daniela.pugliese@ 123456policlinicogemelli.it
                Author notes
                [* ]Correspondence: luisa.guidi@ 123456policlinicogemelli.it ; Tel.: +39-06-30151
                Author information
                https://orcid.org/0000-0003-1572-0118
                https://orcid.org/0000-0003-3320-7094
                Article
                jcm-10-00853
                10.3390/jcm10040853
                7922976
                33669579
                178a92d2-f900-4bb2-992a-0b0df5751951
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 January 2021
                : 11 February 2021
                Categories
                Review

                inflammatory bowel disease,biological therapy,predictors,biomarkers

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