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Neri B, Mancone R, Fiorillo M, Schiavone SC, Migliozzi S, Biancone L. Efficacy and Safety of Janus Kinase-Inhibitors in Ulcerative Colitis. J Clin Med 2024; 13:7186. [PMID: 39685645 DOI: 10.3390/jcm13237186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/17/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
Background: Janus kinase-inhibitors (JAK-i) have recently been approved for treating patients with Ulcerative Colitis (UC); therefore, further information is needed, particularly regarding efficacy and safety. Objectives: To provide a comprehensive review regarding the efficacy and safety of currently available JAK-i in UC. Methods: The PubMed and Scopus databases were considered, searching for 'JAK', 'JAK-inhibitor', 'Janus Kinases', 'Tofacitinib', 'Filgotinib', 'Upadacitinib', individually or in combination with 'IBD', 'Ulcerative Colitis', 'safety', 'efficacy', 'study' and 'trial'. The search was focused on full-text papers published in English, with no publication date restrictions. Results: The efficacy and safety of JAK-i approved for treating patients with UC have been summarized. These included Tofacitinib, Filgotinib and Upadacitinib. Findings from both clinical trials and real-life studies in UC were reported, with particular regard to their efficacy in inducing clinical response and remission, steroid-free remission and endoscopic and histological healing. Overall, JAK-i proved to be effective and safe in selected subgroups of patients with UC. The rapid onset of action and the oral route of administration represent the most relevant characteristics of these drugs. Safety concerns using Tofacitinib in subgroups of patients (infections, hypercholesterolemia, venous thromboembolism and cardiovascular events) were initially raised. More recently, all JAK-i for UC showed an overall satisfactory safety profile. However, indication should be carefully given. Conclusions: The use of JAK-i UC is promising, although no predictive markers of response are currently available. Optimizing their use, as monotherapy or combined with other immunomodulators, may increase their efficacy in appropriately selected subgroups of patients with UC.
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Affiliation(s)
- Benedetto Neri
- Gastroenterology Unit, Department of Systems Medicine, University "Tor Vergata" of Rome, 00133 Rome, Italy
| | - Roberto Mancone
- Gastroenterology Unit, Department of Systems Medicine, University "Tor Vergata" of Rome, 00133 Rome, Italy
| | - Mariasofia Fiorillo
- Gastroenterology Unit, Department of Systems Medicine, University "Tor Vergata" of Rome, 00133 Rome, Italy
| | - Sara Concetta Schiavone
- Gastroenterology Unit, Department of Systems Medicine, University "Tor Vergata" of Rome, 00133 Rome, Italy
| | - Stefano Migliozzi
- Gastroenterology Unit, Department of Systems Medicine, University "Tor Vergata" of Rome, 00133 Rome, Italy
| | - Livia Biancone
- Gastroenterology Unit, Department of Systems Medicine, University "Tor Vergata" of Rome, 00133 Rome, Italy
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Changela M, Pandey S, Bahirwani J, Patel N, Kaneriya M, Basida SD, Shah A, Thakur R, Bodrya K, Jai Kumar Ahuja S, Schneider Y. Protective effects of long term antiplatelet and anticoagulant therapy in hospitalized patients with inflammatory bowel disease. World J Gastrointest Pharmacol Ther 2024; 15:95532. [PMID: 39534521 PMCID: PMC11551617 DOI: 10.4292/wjgpt.v15.i6.95532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 08/25/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD), with its rising prevalence rates is associated with an increased risk of cardiovascular and thromboembolic events. Antiplatelets and/or anticoagulants agents are often prescribed but the literature on the impact of long-term anticoagulation and/or antiplatelet use among patients hospitalized with IBD is scarce. The aim of this study is to assess the outcomes of patients hospitalized with IBD on antiplatelet and/or anticoagulant agents. AIM To investigate the effects of long-term use of antiplatelets/anticoagulants on clinical outcomes in patients hospitalized with IBD. METHODS We conducted a retrospective cohort study using the Nationwide Inpatient Sample database, including all adult IBD patients hospitalized in the United States from 2016 to 2019. Patient cohorts were stratified based on antiplatelet/anticoagulant therapy status. Multivariate regression analysis was done to assess outcomes, adjusting for potential confounders. The primary outcome was mortality, whereas length of stay (LOS), total parenteral nutrition, acute kidney injury, sepsis, shock, gastrointestinal bleeding, need for colonoscopy/sigmoidoscopy, abdominal surgery and total hospitalization charges were secondary outcomes. RESULTS Among 374744 hospitalized IBD patients, antiplatelet or anticoagulant therapy alone was associated with significantly lower in-hospital mortality and reduced healthcare utilization, including shorter LOS and decreased hospitalization costs. Combined therapy was associated with a protective effect on mortality, but did not reach statistical significance. Notably, therapy did not exacerbate disease severity or complications, although higher odds of gastrointestinal bleeding were observed. CONCLUSION Our study highlights the potential benefits of long-term anticoagulation/antiplatelet therapy in hospitalized IBD patients, with improved mortality outcomes and healthcare utilization. While concerns regarding gastrointestinal bleeding exist, the overall safety profile suggests a role for these agents in mitigating thromboembolic risks without exacerbating disease severity. Further research is needed to look at optimal treatment strategies and addressing limitations to guide clinical decision-making in this population.
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Affiliation(s)
- Madhav Changela
- Department of Internal Medicine, One Brooklyn Health System/Interfaith Medical Center, Brooklyn, NY 11213, United States
| | - Sagar Pandey
- Department of Internal Medicine, One Brooklyn Health System/Interfaith Medical Center, Brooklyn, NY 11213, United States
| | - Janak Bahirwani
- Department of Gastroenterology, St. Luke's University Health Network, Bethlehem, PA 18015, United States
| | - Nishit Patel
- Department of Gastroenterology, St. Luke's University Health Network, Bethlehem, PA 18015, United States
| | - Maulik Kaneriya
- Department of Internal Medicine, One Brooklyn Health System/Interfaith Medical Center, Brooklyn, NY 11213, United States
| | - Sanket D Basida
- Department of Internal Medicine, University of Missouri, Columbia, MO 65212, United States
| | - Anish Shah
- Department of Internal Medicine, Bronxcare Health System, Bronx, NY 10457, United States
| | - Rahul Thakur
- Department of Internal Medicine, Albert Einstein College of Medicine/Jacobi Medical Center, Bronx, NY 10461, United States
| | - Krishna Bodrya
- Department of Internal Medicine, Lehigh Valley Health Network, Easton, PA 18045, United States
| | | | - Yecheskel Schneider
- Department of Gastroenterology, St. Luke's University Health Network, Bethlehem, PA 18015, United States
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Meng MJ, Chung CS, Chang CW, Pan YB, Kuo CJ, Chiu CT, Le PH. The Incidence and Predictive Factors of Thromboembolism During Hospitalizations for Inflammatory Bowel Disease Flare-Ups: A Retrospective Cohort Study in Taiwan. J Eval Clin Pract 2024. [PMID: 39494705 DOI: 10.1111/jep.14231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 08/17/2024] [Accepted: 10/17/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND/AIMS Thromboembolism (TE) notably increase morbidity and mortality among inflammatory bowel disease (IBD) patients. Despite ECCO's 2024 guidelines advocating routine anticoagulant prophylaxis, its application in Asia remains inconsistent due to a lack of regional studies. This research investigates the incidence and predictors of TE during IBD-related hospitalizations in Taiwan, aiming to improve prevention strategies. MATERIALS AND METHODS Our retrospective cohort study included 282 adult IBD patients, accounting for 515 flare-up related hospitalizations at Linkou Chang Gung Memorial Hospital from January 2001 to March 2024. Patients were classified into two groups based on the occurrence of TE. RESULTS The incidence of TE was 1.55%. The TE group had significantly lower body weight, body mass index (BMI), hemoglobin and albumin levels but higher rate of sepsis and concurrent autoimmune diseases compared to the non-TE group. Multivariate analysis indicated that concurrent autoimmune diseases and hypoalbuminemia were independent predictors of TE. The optimal serum albumin cutoff was established at 3.01 g/dL, with sensitivities and specificities of 87.5% and 77.3%, respectively. CONCLUSIONS This pioneering Asian study identifies concurrent autoimmune diseases and low serum albumin as key predictors of TE in hospitalized IBD patients. We recommend targeted anticoagulant prophylaxis for IBD patients with these risk factors, especially when serum albumin falls below 3.01 g/dL.
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Affiliation(s)
- Ming-Jung Meng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chen-Shuan Chung
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Chen-Wang Chang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
| | - Yu-Bin Pan
- Biostatistical Section, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chia-Jung Kuo
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan
- Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan
| | - Cheng-Tang Chiu
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan
- Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan
| | - Puo-Hsien Le
- Chang Gung Inflammatory Bowel Disease Center, Linkou, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Linkou, Taoyuan, Taiwan
- Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taoyuan, Taiwan
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Sharma N, Tewatia P, Harvey PR, Kumar A. Controversies in Venous Thromboembolism Risk Assessment in Inflammatory Bowel Disease: A Narrative Review. Diagnostics (Basel) 2024; 14:2112. [PMID: 39410515 PMCID: PMC11476391 DOI: 10.3390/diagnostics14192112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 09/10/2024] [Accepted: 09/20/2024] [Indexed: 10/20/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract with increasing rates of incidence and prevalence across the world. Complex inflammatory and prothrombotic pathophysiology in IBD makes venous thromboembolism (VTE) a common complication with significant morbidity and mortality. This risk is increased in pregnancy. As we continue to understand the pathogenesis of IBD, this article highlights the continued risk of VTE following discharge, for which there is currently no clear guidance, yet the risk of VTE remains high. Furthermore, we discuss this increased VTE risk in the context of pregnant IBD patients and the relevant current guidelines. Alongside this, medications that are used to manage IBD carry their own thrombotic risk, which clinicians should be aware of. Assessing VTE risks in IBD populations using newer medications should be a focus of future research.
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Affiliation(s)
| | | | - Philip R. Harvey
- Department of Gastroenterology, The Royal Wolverhampton NHS Trust, Wolverhampton WV10 0QP, UK; (N.S.); (P.T.); (A.K.)
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Faggiani I, Fanizza J, D’Amico F, Allocca M, Zilli A, Parigi TL, Barchi A, Danese S, Furfaro F. Extraintestinal Manifestations in Inflammatory Bowel Disease: From Pathophysiology to Treatment. Biomedicines 2024; 12:1839. [PMID: 39200303 PMCID: PMC11351332 DOI: 10.3390/biomedicines12081839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/02/2024] [Accepted: 08/09/2024] [Indexed: 09/02/2024] Open
Abstract
The inflammatory bowel diseases (IBDs) are systemic conditions that affect not only the gastrointestinal tract but also other parts of the body. The presence of extraintestinal manifestations can significantly impact the quality of life in IBD patients. Peripheral arthritis, episcleritis, and erythema nodosum are frequently associated with active intestinal inflammation and often improve with standard treatment targeting intestinal inflammation. In contrast, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis typically occur independently of disease flares. The incidence of these conditions in individuals with IBD can reach up to 50% of patients over the course of their lifetime. In addition, some advanced therapies utilized for the treatment of IBD potentially result in side effects that may resemble extraintestinal manifestations. This review provides a thorough analysis of the pathophysiology and treatment of extraintestinal manifestations associated with Crohn's disease and ulcerative colitis.
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Affiliation(s)
- Ilaria Faggiani
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Jacopo Fanizza
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Alberto Barchi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
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Neri B, Mancone R, Fiorillo M, Schiavone SC, De Cristofaro E, Migliozzi S, Biancone L. Comprehensive overview of novel chemical drugs for ulcerative colitis: focusing on phase 3 and beyond. Expert Opin Pharmacother 2024; 25:485-499. [PMID: 38591242 DOI: 10.1080/14656566.2024.2339926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 04/03/2024] [Indexed: 04/10/2024]
Abstract
INTRODUCTION Despite the growing number of highly efficacious biologics and chemical drugs for ulcerative colitis (UC), steroid-free disease control is still difficult to achieve in subgroups of patients due to refractoriness, adverse events, primary or secondary failure. New treatments are therefore still required in order to optimize clinical management of patients with UC. AREAS COVERED The efficacy and safety of both currently available and newly developed small molecules have been summarized. The PubMed database and clinicaltrials.gov were considered in order to search for phase 2b and 3 trials on new chemical drugs for UC. The study drugs reviewed included Janus kinases (JAK) and sphingosine-1-phosphate receptor (S1Pr) inhibitors, α4 integrin antagonist, and micro-RNA-124 upregulators. EXPERT OPINION Rapidity of onset, low immunogenicity, and safety are the main characteristics of small molecules currently available or under evaluation for treatment patients with UC. Among the currently available chemical drugs, the selective JAK and the S1Pr inhibitors are characterized by a good safety profile combined with the ability to induce clinical remission in UC. A relatively low frequency of endoscopic improvement and healing currently appears associated with their use, being higher in UC patients treated with S1Pr inhibitor Etrasimod. Overall, additional new safe and effective drugs are still required in order to optimize disease control in a larger majority of UC patients.
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Affiliation(s)
- Benedetto Neri
- Department of Systems Medicine, Gastroenterological Unit, University "Tor Vergata" of Rome, Rome, Italy
| | - Roberto Mancone
- Department of Systems Medicine, Gastroenterological Unit, University "Tor Vergata" of Rome, Rome, Italy
| | - Mariasofia Fiorillo
- Department of Systems Medicine, Gastroenterological Unit, University "Tor Vergata" of Rome, Rome, Italy
| | - Sara Concetta Schiavone
- Department of Systems Medicine, Gastroenterological Unit, University "Tor Vergata" of Rome, Rome, Italy
| | - Elena De Cristofaro
- Department of Systems Medicine, Gastroenterological Unit, University "Tor Vergata" of Rome, Rome, Italy
| | - Stefano Migliozzi
- Department of Systems Medicine, Gastroenterological Unit, University "Tor Vergata" of Rome, Rome, Italy
| | - Livia Biancone
- Department of Systems Medicine, Gastroenterological Unit, University "Tor Vergata" of Rome, Rome, Italy
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Sinha T, Zain Z, Bokhari SFH, Waheed S, Reza T, Eze-Odurukwe A, Patel M, Almadhoun MKIK, Hussain A, Reyaz I. Navigating the Gut-Cardiac Axis: Understanding Cardiovascular Complications in Inflammatory Bowel Disease. Cureus 2024; 16:e55268. [PMID: 38558708 PMCID: PMC10981543 DOI: 10.7759/cureus.55268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/29/2024] [Indexed: 04/04/2024] Open
Abstract
Inflammatory bowel disease (IBD) presents a complex interplay of chronic inflammation in the gastrointestinal tract and is associated with various extraintestinal manifestations, including cardiovascular complications (CVCs). IBD patients face an elevated risk of CVCs, including coronary artery disease, heart failure, arrhythmias, stroke, peripheral artery disease, venous thromboembolism, and mesenteric ischemia, necessitating comprehensive cardiovascular risk assessment and management. The intricate interplay between chronic inflammation, genetic predisposition, environmental factors, and immune dysregulation likely contributes to the development of CVCs in IBD patients. While the exact mechanisms linking IBD and CVCs remain speculative, potential pathways may involve shared inflammatory pathways, endothelial dysfunction, dysbiosis of the gut microbiome, and traditional cardiovascular risk factors exacerbated by the chronic inflammatory state. Moreover, IBD medications, particularly corticosteroids, may impact cardiovascular health by inducing hypertension, insulin resistance, and dyslipidemia, further amplifying the overall CVC risk. Lifestyle factors such as smoking, obesity, and dietary habits may also exacerbate cardiovascular risks in individuals with IBD. Lifestyle modifications, including smoking cessation, adoption of a heart-healthy diet, regular exercise, and optimization of traditional cardiovascular risk factors, play a fundamental role in mitigating CVC risk. Emerging preventive strategies targeting inflammation modulation and gut microbiome interventions hold promise for future interventions, although further research is warranted to elucidate their efficacy and safety profiles in the context of IBD. Continued interdisciplinary collaboration, advanced research methodologies, and innovative interventions are essential to address the growing burden of CVCs in individuals living with IBD and to improve their long-term cardiovascular outcomes.
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Affiliation(s)
- Tanya Sinha
- Medical Education, Tribhuvan University, Kirtipur, NPL
| | - Zukhruf Zain
- Family Medicine, Aga Khan University Hospital, Karachi, PAK
| | | | - Sarosh Waheed
- Medicine, Gujranwala Medical College, Gujranwala, PAK
| | - Taufiqa Reza
- Medicine, Avalon University School of Medicine, Youngstown, USA
| | | | - Mitwa Patel
- Medicine, David Tvildiani Medical University, Tbilisi, GEO
| | | | | | - Ibrahim Reyaz
- Internal Medicine, Christian Medical College and Hospital, Ludhiana, IND
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