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      Optimal Management of Refractory Crohn’s Disease: Current Landscape and Future Direction

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          Abstract

          Refractory Crohn’s disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn’s disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn’s disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.

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          Most cited references83

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          STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD

          The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD.
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            Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial.

            This study evaluated the efficacy and safety of adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn's disease (CD). Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn's Disease Activity Index > or =70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Co-primary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score <150) at weeks 26 and 56. The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug.
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              Psoriasis Pathogenesis and Treatment

              Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs.
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                Author and article information

                Journal
                Clin Exp Gastroenterol
                Clin Exp Gastroenterol
                ceg
                Clinical and Experimental Gastroenterology
                Dove
                1178-7023
                26 March 2024
                2024
                : 17
                : 75-86
                Affiliations
                [1 ]Department of Medicine, Duke University School of Medicine , Durham, NC, USA
                [2 ]Department of Gastroenterology, New York University School of Medicine , New York, NY, USA
                Author notes
                Correspondence: Adam S Faye, Medicine & Population Health, NYU Langone Division of Gastroenterology, New York University , 303 East 33rd Street, New York, NY, 10016, USA, Tel +1 (855) 698-4232, Fax +1 212-263-3096, Email adam.faye@nyulangone.org
                Author information
                http://orcid.org/0000-0002-0171-7121
                http://orcid.org/0000-0002-1724-0735
                Article
                359376
                10.2147/CEG.S359376
                10981422
                38558912
                280ba714-a18f-4c1a-9322-8a802734b6d0
                © 2024 Lee et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 24 January 2024
                : 22 March 2024
                Page count
                Figures: 1, References: 83, Pages: 12
                Funding
                Funded by: funding;
                There is no funding to report.
                Categories
                Review

                Gastroenterology & Hepatology
                crohn’s disease,surgery,advanced therapies,biologics
                Gastroenterology & Hepatology
                crohn’s disease, surgery, advanced therapies, biologics

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