Alimentary Pharmacology & Therapeutics最新文献

{"title":"Inflammatory bowel disease in 2024 and beyond","authors":"Richard B. Gearry, Cynthia H. Seow, Sreedhar Subramanian","doi":"10.1111/apt.18295","DOIUrl":"10.1111/apt.18295","url":null,"abstract":"<p>In 1987, Professor Roy Pounder launched <i>Alimentary Pharmacology and Therapeutics</i> and in that very issue, he was the senior author on a retrospective study of cyclosporin for the management of Crohn's disease.<span><sup>1</sup></span> Since that time, the incidence and prevalence of inflammatory bowel disease (IBD) has risen exponentially, reaching all corners of the globe and all ethnicities. <i>Alimentary Pharmacology and Therapeutics</i> has provided gastroenterologists with a broad spectrum of clinically relevant journal articles for 37 years through 60 volumes of high-quality publications. The breadth of these is reflected in the range of journal articles that we have assembled for this special IBD edition of <i>Alimentary Pharmacology and Therapeutics</i>. Looking back through the journal listings, this is the ninth special edition focused on IBD, but the first for 16 years. As associate editors, we are proud of this collection of cutting-edge reviews written by an exceptional group of IBD experts, all with strong connections to the journal.</p><p>In 1987, the possibility of disease prevention would have seemed fanciful. However, as we learn from prevention trials in type 1 diabetes mellitus and rheumatoid arthritis, several critical steps have emerged that need to be followed if we are to advance prediction and prevention. Bronze et al. present a road map for how we can navigate a journey to IBD prevention via validated predictive biomarkers to develop a multi-dimensional predictive tool. While science advances, we must also be aware of ethical issues including the preferences of first-degree relatives of those with IBD and how we use predictive information. Finally, bringing together expertise and patients in high-risk clinics should enable appropriate prevention trials.<span><sup>2</sup></span></p><p>The question as to what comprises severe IBD has been one that has long vexed clinicians and patients with IBD. Over time, interest has moved from symptoms to both markers of inflammation (endoscopic, histologic and biomarkers) and a more holistic view (quality of life, disability and psychosocial health). Swaminathan et al. walk us through these concepts before defining disease severity and how this includes all these facets of IBD. Understanding how these interact enables clinicians to focus on specific therapeutic targets and improve outcomes for individuals with IBD.<span><sup>3</sup></span></p><p>Understanding the wider burden of disease includes a focus on the gut–brain axis in patients with IBD. Riggott et al. describe the bi-directional relationship between psychological wellbeing and adverse longitudinal disease activity outcomes, and the high prevalence of irritable bowel syndrome-type symptoms. Treatments that target the gut–brain axis include behavioural treatments, neuromodulators and dietary interventions. Proactive management of psychological health is a critical component in the overall disease management of IBD pati","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"60 9","pages":"1164-1165"},"PeriodicalIF":6.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review article: Novel therapies in inflammatory bowel disease – An update for clinicians","authors":"Nurulamin M. Noor,&nbsp;Aoibh Bourke,&nbsp;Sreedhar Subramanian","doi":"10.1111/apt.18294","DOIUrl":"10.1111/apt.18294","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Several new treatments including small molecules and biologics have been approved for the treatment of inflammatory bowel diseases in recent years. Clinicians and patients now have a wide variety of therapeutic options to choose from and these novel therapies provide several advantages including oral administration, lower immunogenicity, better selectivity and arguably better safety profiles. An increase in treatment options has increased the complexity of decision-making. Both patients and clinicians have had to become rapidly familiar with efficacy of new medications balanced against a range of pre-initiation requirements, dosing schedules and adverse event profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To provide a simple guide to practising clinicians on recently approved and emerging therapies and address key challenges around treatment strategies such as optimal sequencing and timing of treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We comprehensively searched the published literature and major conference abstracts to identify phase III placebo-controlled and active comparator trials for Crohn's disease and ulcerative colitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data for recently approved therapies including selective Janus kinase inhibitors, sphingosine-1 receptor modulators and p19 interleukin (IL)-23 inhibitors have demonstrated improved patient outcomes in both Crohn's disease and ulcerative colitis. Further comparative head-to-head studies have improved our understanding of when and how to optimally use newer therapies, specifically for IL-23 inhibitors. Data for emerging treatment options and novel treatment strategies such as early effective treatment, combinations of treatments and implications for sequencing are continuing to transform IBD care continually.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Recently approved novel therapies have expanded the range of medical options available to treat IBD. However, further data from long-term extension studies, real-world studies and head-to-head trials are warranted to better inform the long-term safety and optimal sequencing of treatments for patients living with IBD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"60 9","pages":"1244-1260"},"PeriodicalIF":6.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review article: Prevention of inflammatory bowel disease—The path forward","authors":"Sérgio Bronze,&nbsp;Manasi Agrawal,&nbsp;Jean-Frédéric Colombel,&nbsp;Joana Torres,&nbsp;Ryan C. Ungaro","doi":"10.1111/apt.18263","DOIUrl":"https://doi.org/10.1111/apt.18263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The possibility of preventing inflammatory bowel disease (IBD) is becoming more plausible due to advances in understanding preclinical disease and successful prevention trials in other immune-mediated diseases, such as type 1 diabetes and rheumatoid arthritis. However, before that possibility becomes reality, several efforts need to occur in parallel and in a coordinated way.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To propose some critical steps necessary for advancing the field of IBD prediction and prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We reviewed the current literature to identify the necessary steps toward a preventive strategy for IBD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The first step should determine the most robust predictive biomarkers and validate them across independent cohorts, creating a multidimensional predictive tool. The second step is to gain a better understanding of the preferences of first-degree relatives and people at risk for IBD, informing the implementation of screening and preventive strategies. Third, these efforts should contribute to the development of high-risk clinics and establish the necessary networks for disease prevention trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Advancing the field of IBD prediction and prevention will require a multifaceted approach, integrating biomarker discovery, understanding patient preferences, and establishing infrastructure for a collaborative network to support the practical implementation of IBD prevention strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"60 9","pages":"1166-1175"},"PeriodicalIF":6.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review article: Measuring disease severity in inflammatory bowel disease – Beyond treat to target","authors":"Akhilesh Swaminathan,&nbsp;Andrew S. Day,&nbsp;Miles P. Sparrow,&nbsp;Laurent Peyrin-Biroulet,&nbsp;Corey A. Siegel,&nbsp;Richard B. Gearry","doi":"10.1111/apt.18231","DOIUrl":"https://doi.org/10.1111/apt.18231","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To perform this narrative review, a Medline search was conducted for full-text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality-of-life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"60 9","pages":"1176-1199"},"PeriodicalIF":6.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Trial Design Considerations for Hospitalised Patients With Ulcerative Colitis Flares and Application to Study Hyperbaric Oxygen Therapy in the NIDDK HBOT-UC Consortium.","authors":"Parambir S Dulai,Lauren Balmert Bonner,Charlotte Sadler,Laura E Raffals,Gursimran Kochhar,Peter Lindholm,Jay C Buckey,Gary N Toups,Libeth Rosas,Neeraj Narula,Vipul Jairath,Sailish Honap,Laurent Peyrin-Biroulet,Bruce E Sands,Stephen B Hanauer,Denise M Scholtens,Corey A Siegel,","doi":"10.1111/apt.18326","DOIUrl":"https://doi.org/10.1111/apt.18326","url":null,"abstract":"BACKGROUNDPatients with ulcerative colitis (UC) who are hospitalised for acute severe flares represent a high-risk orphan population.AIMTo provide guidance for clinical trial design methodology in these patients.METHODSWe created a multi-centre consortium to design and conduct a clinical trial for a novel therapeutic intervention (hyperbaric oxygen therapy) in patients with UC hospitalised for moderate-severe flares. During planning, we identified and addressed specific gaps for inclusion/exclusion criteria; disease activity measures; pragmatic trial design considerations within care pathways for hospitalised patients; standardisation of care delivery; primary and secondary outcomes; and sample size and statistical analysis approaches.RESULTSThe Truelove-Witt criteria should not be used in isolation. Endoscopy is critical for defining eligible populations. Patient-reported outcomes should include rectal bleeding and stool frequency, with secondary measurement of urgency and nocturnal bowel movements. Trial design needs to be tailored to care pathways, with early intervention focused on replacing and/or optimising responsiveness to steroids and later interventions focused on testing novel rescue agents or strategies. The PRECIS-2 framework offers a means of tailoring to local populations. We provide standardisation of baseline testing, venous thromboprophylaxis, steroid dosing, discharge criteria and post-discharge follow-up to avoid confounding by usual care variability. Statistical considerations are provided given the small clinical trial nature of this population.CONCLUSIONWe provide an outline for framework decisions made for the hyperbaric oxygen trial in patients hospitalised for UC flares. Future research should focus on the remaining gaps identified.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"230 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review article: Optimisation of biologic (monoclonal antibody) therapeutic response in inflammatory bowel disease","authors":"Thanaboon Chaemsupaphan,&nbsp;Rupert W. Leong,&nbsp;Niels Vande Casteele,&nbsp;Cynthia H. Seow","doi":"10.1111/apt.18228","DOIUrl":"https://doi.org/10.1111/apt.18228","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There are a plethora of therapeutic options for the management of inflammatory bowel disease (IBD). Despite this, clinical outcomes with standard dosing often fall short of established targets. While efforts centre on developing novel therapies, there is an ongoing need to optimise the use of existing agents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To focus on strategies to optimise response to biologic (monoclonal antibody) therapies in IBD, including use of therapeutic drug monitoring (TDM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An extensive review of the published literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TDM is a strategy aimed at enhancing the effectiveness of drugs with variable exposure-response relationships by measuring serum concentrations of biologic therapies and detecting neutralising antibodies. Reactive TDM is performed when therapeutic goals have not been achieved. Tumour necrosis factor alpha (TNF) inhibitors are the treatment class most frequently associated with immunogenicity and loss of response. Immunogenicity can be reduced through avoidance of low serum drug concentrations by dose optimisation or use of concomitant immunomodulator therapy. Subtherapeutic dosing in the absence of antidrug antibodies is best managed by dose escalation or dose interval reduction. Persistent neutralising drug antibodies necessitate switching to an alternative therapy. Proactively ensuring adequate serum trough levels might help sustain treatment durability and prevent loss of response. Newer non-TNF inhibitors demonstrate less robust exposure-response relationships, and TDM may not prove as beneficial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In the treat-to-target paradigm of IBD treatment, optimising treatment effect with dose optimisation, which may involve strategies including TDM, increases the likelihood of achieving clinical remission and may accomplish deeper levels of remission beyond symptom control.</p>\u0000 </section>\u0000 </div>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"60 9","pages":"1234-1243"},"PeriodicalIF":6.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.18228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Checkpoint Inhibitor‐Induced Liver Injury—Time to Abandon CTCAE? Authors' Reply","authors":"Lina Hountondji, Lucy Meunier","doi":"10.1111/apt.18343","DOIUrl":"https://doi.org/10.1111/apt.18343","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"15 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Checkpoint Inhibitor‐Induced Liver Injury—Time to Abandon CTCAE?","authors":"Kelly Torosian, Shravan Dave","doi":"10.1111/apt.18308","DOIUrl":"https://doi.org/10.1111/apt.18308","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"17 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Hepatoprotective Effects of Medications Used in Diabetes Mellitus—Optimal Glycaemic Control Is Just the Tip of the Iceberg","authors":"Osman Cagin Buldukoglu, Serkan Ocal, Ayhan Hilmi Cekin","doi":"10.1111/apt.18342","DOIUrl":"https://doi.org/10.1111/apt.18342","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"13 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142415689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: A Positive High‐Sensitivity HBsAg Test Was Significantly Associated With Poorer Prognosis in Patients With Non‐HBV‐Related HCC—Authors' Reply","authors":"Naohiro Yasuura, Goki Suda, Masatsugu Ohara, Naoya Sakamoto","doi":"10.1111/apt.18340","DOIUrl":"https://doi.org/10.1111/apt.18340","url":null,"abstract":"LINKED CONTENTThis article is linked to Yasuura et al papers. To view these articles, visit <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"https://doi.org/10.1111/apt.18229\">https://doi.org/10.1111/apt.18229</jats:ext-link> and <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"https://doi.org/10.1111/apt.18300\">https://doi.org/10.1111/apt.18300</jats:ext-link>.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}