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Hisamatsu T, Kobayashi T, Motoya S, Fujii T, Kunisaki R, Shibuya T, Matsuura M, Hiraoka S, Takeuchi K, Yasuda H, Yokoyama K, Takatsu N, Maemoto A, Tahara T, Tominaga K, Shimada M, Kuno N, Fernandez JL, Hirose L, Ishiguro K, Cavaliere M, Hibi T. Real-World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study. J Gastroenterol Hepatol 2025. [PMID: 40370285 DOI: 10.1111/jgh.16936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/31/2025] [Accepted: 03/01/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND AND AIM Vedolizumab (VDZ) is often used in older patients with ulcerative colitis (UC) in clinical practice; however, real-world evidence is still limited, including in those with late-onset UC. METHODS This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late-onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]). RESULTS There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.5% vs. 47.6%, p = 0.9174; week 14: 62.5% vs. 54.8%, p = 0.1317; week 54: 47.5% vs. 46.4%, p = 0.8149), primary nonresponse (10.0% vs. 15.5%, p = 0.6248), loss of response (12.5% vs. 9.4%, p = 0.5675), or overall safety. Among patients ≥ 70 years, the incidence of adverse drug reactions was numerically greater in those with concomitant corticosteroids than in those without. For older patients with and without late-onset UC, week 54 remission rates were 23.1% versus 57.7% (p = 0.0544); surgery was reported in 3/13 versus 2/26 patients and hospitalization in 5/13 versus 6/26 patients. One death was reported in patients with late-onset UC. CONCLUSIONS VDZ effectiveness and safety were similar in patients ≥ 70 and < 70 years; VDZ may be a suitable treatment option for patients ≥ 70 years with UC. Patients with late-onset UC tended to have more frequent surgery/hospitalization and lower effectiveness than those without, possibly necessitating greater caution when using VDZ. TRIAL REGISTRATION Japanese Registry of Clinical Trials registration number: jRCT-1080225363.
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Affiliation(s)
- Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Satoshi Motoya
- Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Sakiko Hiraoka
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Ken Takeuchi
- Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha, Kashiwa, Chiba, Japan
| | - Hiroshi Yasuda
- Department of Gastroenterology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Kaoru Yokoyama
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Noritaka Takatsu
- Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan
| | - Atsuo Maemoto
- Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
| | - Toshiyuki Tahara
- Department of Gastroenterology, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan
| | - Keiichi Tominaga
- Department of Gastroenterology, Dokkyo Medical University, Mibu, Tochigi, Japan
| | - Masaaki Shimada
- Department of Gastroenterology, NHO Nagoya Medical Center, Nagoya, Japan
| | - Nobuaki Kuno
- Department of Gastroenterology and Medicine, Fukuoka University Hospital, Fukuoka, Japan
| | | | - Lisa Hirose
- Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan
| | - Kaori Ishiguro
- Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan
| | - Mary Cavaliere
- Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
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Wewer MD, Letnar G, Andersen KK, Malham M, Wewer V, Seidelin JB, Bendtsen F, Burisch J. Thiopurines and the Risk of Cancer in Patients With Inflammatory Bowel Disease and Reference Individuals Without Inflammatory Bowel Disease: A Danish Nationwide Cohort Study (1996-2018). Clin Gastroenterol Hepatol 2025; 23:1030-1038. [PMID: 39209201 DOI: 10.1016/j.cgh.2024.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 08/14/2024] [Accepted: 08/15/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND & AIMS Thiopurine therapy is a cornerstone in the treatment of inflammatory bowel disease (IBD). We aimed to assess the effect of thiopurines on cancer risk in IBD according to drug exposure and age. METHODS Danish national registers were used to identify incident IBD patients, exposure to drugs, and status of cancers, in 1996 to 2018. Cox regressions were used to compare cancer risks in IBD and non-IBD individuals and to assess IBD patients' cumulative drug exposure and the association to first cancer, excluding non-melanoma skin cancer. RESULTS We followed 43,419 patients with IBD for a median of 8.2 years (interquartile range, 3.7-14.2 years) after IBD diagnosis. Cancer was reported in 3128 (7.2%) patients with IBD. The risk of cancer was increased in patients with IBD in all age categories compared with non-IBD individuals (<50 years: adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.43-1.77; 50-65 years: aHR, 1.31; 95% CI, 1.19-1.44; and >65 years: aHR, 1.14; 95% CI, 1.05-1.24). Monotherapy (aHR, 1.36; 95% CI, 1.17-1.57) and combination therapy (aHR, 2.49; 95% CI, 1.64-3.78) were associated with an increased risk of cancer compared to unexposed patients with IBD. Among elderly patients (>65 years), the aHR was 2.79 (95% CI, 1.24-6.28) in those receiving combination therapy. In patients discontinuing thiopurines, aHRs returned to the level of unexposed (aHR, 0.89; 95% CI, 0.78-1.01). The aHR was positively associated with cumulative thiopurine exposure and in patients with >5 years of exposure, reaching an aHR of 1.36 (95% CI, 1.15-1.61). CONCLUSIONS Thiopurines were associated with increased hazard of cancer, especially when used in combination therapy in the elderly. The hazard increased by 36% when patients were exposed to thiopurines for more than 5 years. Reassuringly, the hazard returned to baseline after discontinuation of thiopurines.
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Affiliation(s)
- Mads Damsgaard Wewer
- Gastro Unit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark.
| | | | | | - Mikkel Malham
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark; The Department of Paediatrics and Adolescent Medicine, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Vibeke Wewer
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark; The Department of Paediatrics and Adolescent Medicine, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Benedict Seidelin
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Gastro Unit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Wang S, Wu Y, Fei B, Zhang M. Fluorescent Nanocomposite Materials with Synergistic Effects for Enhanced Fenelidone Delivery in Diabetic Nephropathy Treatment. J Fluoresc 2025:10.1007/s10895-025-04195-0. [PMID: 39985616 DOI: 10.1007/s10895-025-04195-0] [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: 01/05/2025] [Accepted: 02/09/2025] [Indexed: 02/24/2025]
Abstract
In this study, we designed and synthesized a novel thio-purine analog, compound 1, which exhibits significant fluorescence properties due to its extended conjugated system, heteroatom incorporation (O, S, N), and rigid three-dimensional molecular framework, enabling its use as a fluorescence probe for real-time drug tracking and release monitoring. To enhance the solubility, biocompatibility, and therapeutic efficacy of compound 1, we synthesized a copper(II)-based coordination polymer (CP1) via hydrothermal methods, featuring a three-dimensional framework formed by 1,4-ttb and auxiliary ligand 4,4'-bpdc, as confirmed by comprehensive characterization techniques. Leveraging the synergistic therapeutic effects of compound 1 and fenelidone, we developed a composite drug delivery system, mPEG-PSU@CP1@1@fenelidone, which combines an amphiphilic mPEG-PSU shell with a CP1 core co-encapsulating both drugs. Notably, the fluorescence properties of compound 1 allow for real-time monitoring of drug release, as its fluorescence is quenched when encapsulated in CP1 and restored upon release. This system optimizes controlled drug release while enhancing the synergistic effects of compound 1 and fenelidone in reducing inflammation and renal fibrosis, as demonstrated in diabetic nephropathy (DN) model mice. Overall, the composite system integrates real-time fluorescence monitoring with improved therapeutic efficacy, offering a promising strategy for diabetic nephropathy treatment.
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Affiliation(s)
- Suyu Wang
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yanyan Wu
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Bingru Fei
- Department of Nephrology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, China
| | - Mei Zhang
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
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Garcia JL, Rosa I, da Silva JP, Moleiro J, Claro I. Incidence and risk factors for neoplasia in inflammatory bowel disease. Asia Pac J Clin Oncol 2024; 20:559-564. [PMID: 36915954 DOI: 10.1111/ajco.13908] [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: 04/28/2022] [Revised: 10/22/2022] [Accepted: 11/24/2022] [Indexed: 03/15/2023]
Abstract
INTRODUCTION Inflammatory Bowel Disease (IBD) patients may have an increased risk of neoplasia. The aim was to evaluate the incidence of malignant neoplasia in IBD patients, associated risk factors and therapy adjustments. METHODS Unicentric retrospective cohort study. All patients followed for IBD in a tertiary portuguese hospital and oncological centre during 2015-2020 were included. RESULTS 318 patients were included female 55.0%, age at diagnosis = 37.24(±15,28), Crohn's disease 52.5%, Primary Sclerosing Cholangitis n = 7, family history of cancer n = 12, previous diagnosis of neoplasia n = 23(7.2%). 42 cancers were diagnosed in 35 patients (11.0%) - median of 12.0(IQR = 7.5-21.0) years after IBD diagnosis. Most affected organs were the skin (n = 15 in 11 patients; melanoma = 1), colon/rectum (n = 8 in 6 patients), prostate (n = 4), breast (n = 3) and anal canal (n = 2). In those with non-melanoma skin cancer, 6 were under active treatment with azathioprine and 2 had stopped it for more than two years. In the univariate analysis, the occurrence of neoplasia was positively associated with tobacco exposure (p = 0.022), age at IBD diagnosis (p = 0.021), and negatively with infliximab exposure (p = 0.046). In 9 cases, cancer treatment was different because of the IBD, while IBD treatment was changed in 9 patients. In those affected by cancer, in the univariate analysis, its cure/remission was negatively associated with tobacco exposure (p = 0.004) and positively with salicylates use (p = 0.007). CONCLUSION In IBD patients, cancer mostly affected the skin and the lower digestive system. As in the general population, tobacco exposure was a risk factor for the development of neoplasia.
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Affiliation(s)
- Joana Lemos Garcia
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
| | - Isadora Rosa
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
| | | | - Joana Moleiro
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
| | - Isabel Claro
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
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Singh A, Khanna T, Mahendru D, Kahlon J, Kumar V, Sohal A, Yang J. Insights into renal and urological complications of inflammatory bowel disease. World J Nephrol 2024; 13:96574. [PMID: 39351187 PMCID: PMC11439091 DOI: 10.5527/wjn.v13.i3.96574] [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: 05/13/2024] [Revised: 07/01/2024] [Accepted: 07/15/2024] [Indexed: 09/19/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract, which follows a relapsing and remitting course. Apart from affecting the gastrointestinal tract, IBD also has extra-intestinal manifestations (EIMs). While the etiology of extraintestinal manifestation remains unclear, it is theorized to be based on immunological responses influenced by genetic factors. Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn's disease. The renal manifestations in IBD patients encompass a range of conditions including nephrolithiasis, amyloidosis, tubulointerstitial nephritis, glomerulonephritis (GN), obstructive pathologies, and chronic kidney disease (CKD). The incidence of CKD in IBD patients varies from 5%-15%. The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury, or from complications like recurrent stones, amyloidosis, or GN. Additionally, nephrotoxic medications used in treating IBD, such as TNF-α inhibitors, calcineurin inhibitors, and aminosalicylates, can exacerbate the decline in renal function. Currently, there is a lack of consensus regarding these patients' screening and renal function monitoring. This review aims to assess the existing literature on the different renal complications among individuals with IBD, shedding light on their pathophysiology and management.
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Affiliation(s)
- Anmol Singh
- Department of Medicine, Tristar Centennial Medical Center, Nashville, TN 37203, United States
| | - Tejasvini Khanna
- Department of Medicine, Maulana Azad Medical College, New Delhi 110002, India
| | - Diksha Mahendru
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Jasraj Kahlon
- Department of Internal Medicine, Abrazo Medical Center, Phoenix, AZ 85015, United States
| | - Vikash Kumar
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Juliana Yang
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX 77555, United States
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Strigáč A, Caban M, Małecka-Wojciesko E, Talar-Wojnarowska R. Safety and Effectiveness of Thiopurines and Small Molecules in Elderly Patients with Inflammatory Bowel Diseases. J Clin Med 2024; 13:4678. [PMID: 39200823 PMCID: PMC11355586 DOI: 10.3390/jcm13164678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 08/02/2024] [Accepted: 08/05/2024] [Indexed: 09/02/2024] Open
Abstract
The management of inflammatory bowel diseases (IBD) requires weighing an individual patient's therapeutic benefits and therapy-related complication risks. The immunomodulators that have been commonly used so far in IBD therapy are thiopurines, including 6-mercaptopurine and azathioprine. As our understanding of the IBD pathomechanisms is widening, new therapeutic approaches are being introduced, including the Janus kinase (JAK) inhibitors and Sphingosine 1-phosphate receptor (S1PR) modulators' development. Non-selective JAK inhibitors are represented by tofacitinib, while selective JAK inhibitors comprise filgotinib and upadacitinib. As for the S1PR modulators, ozanimod and etrasimod are approved for UC therapy. The number of elderly patients with IBD is growing; therefore, this review aimed to evaluate the effectiveness and safety of the oral immunomodulators among the subjects aged ≥60. Possible complications limit the use of thiopurines in senior patients. Likewise, the promising effectiveness of new drugs in IBD therapy in those with additional risk factors might be confined by the risk of serious adverse events. However, the data regarding this issue are limited.
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Affiliation(s)
- Aleksandra Strigáč
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (M.C.); (E.M.-W.); (R.T.-W.)
| | - Miłosz Caban
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (M.C.); (E.M.-W.); (R.T.-W.)
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland
| | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (M.C.); (E.M.-W.); (R.T.-W.)
| | - Renata Talar-Wojnarowska
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (M.C.); (E.M.-W.); (R.T.-W.)
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Axelrad JE, Hashash JG, Itzkowitz SH. AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Patients With Malignancy: Commentary. Clin Gastroenterol Hepatol 2024; 22:1365-1372. [PMID: 38752967 DOI: 10.1016/j.cgh.2024.03.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/16/2024] [Accepted: 03/25/2024] [Indexed: 06/23/2024]
Abstract
DESCRIPTION The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) Commentary is to discuss the risks of various malignancies in patients with inflammatory bowel diseases (IBD) and the impact of the available medical therapies on these risks. The CPU will also guide the approach to the patient with IBD who develops a malignancy or the patient with a history of cancer in terms of IBD medication management. METHODS This CPU was commissioned and approved by the AGA Institute CPU committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This communication incorporates important and recently published studies in the field, and it reflects the experiences of the authors who are experts in the diagnosis and management of IBD.
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Affiliation(s)
- Jordan E Axelrad
- Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, NYU Grossman School of Medicine, New York, New York.
| | - Jana G Hashash
- Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida
| | - Steven H Itzkowitz
- Division of Gastroenterology, the Icahn School of Medicine at Mount Sinai, New York, New York
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Moon W, Park JJ. [Risks of Cancer Associated with Therapeutic Drugs for Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 83:233-242. [PMID: 38918036 DOI: 10.4166/kjg.2024.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/21/2024] [Accepted: 06/21/2024] [Indexed: 06/27/2024]
Abstract
Crohn's disease and ulcerative colitis are lifelong chronic inflammatory conditions, with many patients requiring ongoing immunomodulatory drug therapy for maintenance treatment. Recent therapeutic goals in inflammatory bowel disease (IBD) are not only aimed at symptomatic remission but also at achieving mucosal healing to improve the natural course of the disease. In this context, therapeutic approaches are being applied in clinical settings that involve early and appropriate use of drugs, such as immunomodulators or biologics, that have the potential to induce healing of the inflamed intestine before irreversible intestinal damage occurs. All drugs that continuously control intestinal inflammation in IBD can heal the mucosa and potentially reduce the incidence of colitis-associated bowel cancer; however, the continuous use of immunosuppressants can potentially increase the risk of malignancies. The safety issues of the drugs used in clinical practice are partly confirmed during their development processes or shortly after initial marketing, but in other cases, they are estimated through post-marketing case reports or epidemiological studies, sometimes decades after drug approval. This review explores the risks associated with malignancies related to the treatment of IBD, focusing on drugs currently approved in Republic of Korea.
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Affiliation(s)
- Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Jae Jun Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Yuan Z, Ye J, Liu B, Zhang L. Unraveling the role of autophagy regulation in Crohn's disease: from genetic mechanisms to potential therapeutics. ADVANCED BIOTECHNOLOGY 2024; 2:14. [PMID: 39883213 PMCID: PMC11740883 DOI: 10.1007/s44307-024-00021-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 02/29/2024] [Accepted: 03/10/2024] [Indexed: 01/31/2025]
Abstract
Autophagy serves as the primary intracellular degradation mechanism in which damaged organelles and self-cytoplasmic proteins are transported to the lysosome for degradation. Crohn's disease, an idiopathic chronic inflammatory disorder of the gastrointestinal tract, manifests in diverse regions of the digestive system. Recent research suggests that autophagy modulation may be a new avenue for treating Crohn's disease, and several promising small-molecule modulators of autophagy have been reported as therapeutic options. In this review, we discuss in detail how mutations in autophagy-related genes function in Crohn's disease and summarize the modulatory effects on autophagy of small-molecule drugs currently used for Crohn's disease treatment. Furthermore, we delve into the therapeutic potential of small-molecule autophagy inducers on Crohn's disease, emphasizing the prospects for development in this field. We aim to highlight the significance of autophagy modulation in Crohn's disease, with the aspiration of contributing to the development of more efficacious treatments that can alleviate their suffering, and improve their quality of life.
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Affiliation(s)
- Ziyue Yuan
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
| | - Jing Ye
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Bo Liu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Lan Zhang
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.
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Ingrasciotta Y, Grova M, Crispino F, Isgrò V, Calapai F, Macaluso FS, Mattace-Raso F, Trifirò G, Orlando A. Safety and potential interaction of immunosuppressive drugs for the treatment of inflammatory bowel disease in elderly patients. Minerva Gastroenterol (Torino) 2024; 70:98-108. [PMID: 34057333 DOI: 10.23736/s2724-5985.21.02919-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are chronic diseases associated with increased morbidity and reduced quality of life. Age may represent a risk factor for adverse events, due to the multimorbidity and polypharmacy, common in elderly patients. Elderly are often not included in clinical trials evaluating efficacy and safety of study drugs for the treatment of inflammatory bowel diseases. Several drugs, such as aminosalicylates, systemic corticosteroids, immunosuppressant drugs, biological drugs and Janus Kinase inhibitors, are available for the management of inflammatory bowel diseases. Therefore, with the increasing spectrum of therapeutic options it is important to analyze the evidence regarding the safety of the use of these agents in elderly patients. Selection of immunosuppressive therapy is a challenge in the management of elderly patients with inflammatory bowel diseases, for whom biologics with a lower risk of infection or cancer, such as vedolizumab and ustekinumab, may be preferred in elderly patients. Concomitant therapies and comorbidities must be thoroughly investigated before initiating any immunosuppressive or biological therapy in order to minimize the risk of drug-drug interactions. This review aimed to provide an overview of the safety of thiopurines, methotrexate and target therapies as well as their drug-drug interactions in patients with inflammatory bowel diseases.
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Affiliation(s)
- Ylenia Ingrasciotta
- Department of Internal Medicine, Erasmus MC University-Medical Center, Rotterdam, the Netherlands -
- Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy -
| | - Mauro Grova
- Unit of Inflammatory Bowel Disease, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
- Section of Gastroenterology and Hepatology, Internal Medicine and Medical Specialties, Department of Health Promotion Sciences Maternal and Infant Care (PROMISE), University of Palermo, Palermo, Italy
| | - Federica Crispino
- Unit of Inflammatory Bowel Disease, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
- Section of Gastroenterology and Hepatology, Internal Medicine and Medical Specialties, Department of Health Promotion Sciences Maternal and Infant Care (PROMISE), University of Palermo, Palermo, Italy
| | - Valentina Isgrò
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Fabrizio Calapai
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Fabio S Macaluso
- Unit of Inflammatory Bowel Disease, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
| | - Francesco Mattace-Raso
- Department of Internal Medicine, Erasmus MC University-Medical Center, Rotterdam, the Netherlands
| | - Gianluca Trifirò
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Ambrogio Orlando
- Unit of Inflammatory Bowel Disease, A.O.O.R. Villa Sofia-Cervello, Palermo, Italy
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11
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Kim N. Colorectal Diseases and Gut Microbiome. SEX/GENDER-SPECIFIC MEDICINE IN CLINICAL AREAS 2024:137-208. [DOI: 10.1007/978-981-97-0130-8_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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12
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Zhang H, Hu C, Zhang Z, Li P, Shen G, Sun J. Two-sample Mendelian randomization study reveals no causal relationship between inflammatory bowel disease and urological cancers. Front Genet 2023; 14:1275247. [PMID: 38188502 PMCID: PMC10771298 DOI: 10.3389/fgene.2023.1275247] [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: 08/09/2023] [Accepted: 12/06/2023] [Indexed: 01/09/2024] Open
Abstract
Background: The relationship between inflammatory bowel disease (IBD) and urological cancers has been identified in epidemiological and observational studies, while the causality remains uncertain. We examined whether IBD is causally associated with urological cancers in a Mendelian randomization (MR) study. Methods: The causal relationship between IBD, its main subtypes, and urological cancers was investigated using genome-wide association study data. To obtain more reliable conclusions, all outcomes were divided into training and validation sets. Eligible single-nucleotide polymorphisms were selected as instrumental variables based on MR analysis assumptions. The inverse variance-weighted (IVW) method was employed as the main method along with four other complementary methods. Results: In this two-sample MR study, no genetic evidence for the causal effect of IBD on urological cancers was found in either the training or validation sets using the IVW method. Similarly, we did not observe any significant association between Crohn's disease or ulcerative colitis and urological cancers. The results of the other methods are in accordance with those obtained using the IVW method. Conclusion: In this study, we confirmed that IBD is not a causal genetic risk factor for urological cancer in a European population.
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Affiliation(s)
- Haoyang Zhang
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Can Hu
- Department of Urology, Suzhou Xiangcheng People’s Hospital, Suzhou, China
| | - Zhiyu Zhang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Peng Li
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Gang Shen
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Jiale Sun
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
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13
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Liu J, Wu P, Lai S, Wang J, Wang J, Zhang Y. Identifying possible hub genes and biological mechanisms shared between bladder cancer and inflammatory bowel disease using machine learning and integrated bioinformatics. J Cancer Res Clin Oncol 2023; 149:16885-16904. [PMID: 37740761 DOI: 10.1007/s00432-023-05266-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 08/08/2023] [Indexed: 09/25/2023]
Abstract
BACKGROUND Recent studies have shown that inflammatory bowel disease (IBD) is associated with bladder cancer (BC) incidence. But there is still a lack of understanding regarding its pathogenesis. Thus, this study aimed to identify potential hub genes and their important pathways and pathological mechanisms of interactions between IBD and BC using bioinformatics methods. METHODS The data from Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) were analyzed to screen common differentially expressed genes (DEGs) between IBD and BC. The "clusterProfiler" package was used to analyze GO term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment in DEGs. After that, we conducted a weighted gene co-expression network analysis (WGCNA) on these DEGs to determine the vital modules and genes significantly related to BC. Protein-protein interaction (PPI) networks was used to identify hub genes. Further, the hub genes were used to develop a prognostic signature by Cox analysis. The validity of the ten hub DEGs was tested using three classification algorithms. Finally, we analyzed the microRNAs (miRNA)-mRNA, transcription factors (TFs)-mRNA regulatory network. RESULTS Positive regulation of organelle fission, chromosomal region, tubulin binding, and cell cycle signaling pathway were the major enriched pathways for the common DEGs. PPI networks identified three hub proteins (AURKB, CDK1, and CCNA2) with high connectivity. Three machine-learning classification algorithms based on ten hub genes performed well for IBD and BC (accuracy > 0.80). The robust predictive model based on the ten hub genes could accurately classify BC cases with various clinical outcomes. Based on the gene-TFs and gene-miRNAs network construction, 9 TFs and 6 miRNAs were identified as potential critical TFs and miRNAs. There are 13 drugs that interact with the hub gene based on gene-drug interaction analysis. CONCLUSIONS This study explored common gene signatures and the potential pathogenesis of IBD and BC. We revealed that an unbalanced immune response, cell cycle pathway, and neutrophil infiltration might be the common pathogenesis of IBD and BC. Molecular mechanisms for the treatment of IBD and CC still require further investigation.
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Affiliation(s)
- Jianyong Liu
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Beijing Hospital Continence Center, Beijing, People's Republic of China
| | - Pengjie Wu
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Beijing Hospital Continence Center, Beijing, People's Republic of China
| | - Shicong Lai
- Department of Urology, Peking University People's Hospital, Beijing, 100044, People's Republic of China
| | - Jianye Wang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
| | - Jianlong Wang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
| | - Yaoguang Zhang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
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14
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Wang L, Deng JY, Li KP, Shan-Yin, Zhu PY. Inflammatory bowel disease and bladder cancer risk: based on a Mendelian randomization study. BMC Urol 2023; 23:195. [PMID: 38012665 PMCID: PMC10683281 DOI: 10.1186/s12894-023-01346-y] [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: 06/28/2023] [Accepted: 10/20/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Prior epidemiological observational studies have duly documented a correlative link between inflammatory bowel disease (IBD) and bladder cancer (BC); however, the establishment of a definitive causal relationship has remained elusive. The principal objective of this meticulous investigation was to rigorously evaluate the causal nexus between IBD and BC, employing the robust methodology of Mendelian randomization (MR) analysis. METHODS We meticulously performed both univariate and multivariate Mendelian randomization (MVMR) analyses employing publicly accessible genome-wide association study (GWAS) data. The central approach employed for our investigations was inverse variance weighting (IVW) method, while diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger. RESULTS In the univariate MR analysis, no causal link was observed between genetic prediction of IBD and BC. Furthermore, both Crohn's disease (CD) and ulcerative colitis (UC) showed no causal association with BC. The consistent association between CD and UC in the MVMR analysis supports this finding. CONCLUSION This study found no genetic basis for the causative association of IBD and BC. It is crucial to emphasize that further comprehensive investigations are warranted to delve into the intricate underlying mechanisms that may contribute to these associations.
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Affiliation(s)
- Li Wang
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Jing-Ya Deng
- Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Kun-Peng Li
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China
| | - Shan-Yin
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Ping-Yu Zhu
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
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15
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Massano A, Bertin L, Zingone F, Buda A, Visaggi P, Bertani L, de Bortoli N, Fassan M, Scarpa M, Ruffolo C, Angriman I, Bezzio C, Casini V, Ribaldone DG, Savarino EV, Barberio B. Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review. Cancers (Basel) 2023; 15:3824. [PMID: 37568640 PMCID: PMC10417189 DOI: 10.3390/cancers15153824] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. AIMS The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. RESULTS IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. CONCLUSIONS Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.
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Affiliation(s)
- Alessandro Massano
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Luisa Bertin
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Andrea Buda
- Gastroenterology Unit, Department of Gastrointestinal Oncological Surgery, S. Maria del Prato Hospital, 32032 Feltre, Italy;
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Lorenzo Bertani
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine, University of Padova, 35138 Padova, Italy;
| | - Marco Scarpa
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Cesare Ruffolo
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Imerio Angriman
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Cristina Bezzio
- IBD Center, Gastroenterology Unit, Rho Hospital, ASST Rhodense, 20017 Rho, Italy;
| | | | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10126 Turin, Italy;
| | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
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16
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Sharip MT, Subramanian S. IBD in the elderly - beware of pitfalls! Saudi J Gastroenterol 2023; 29:201-203. [PMID: 37470664 PMCID: PMC10445498 DOI: 10.4103/sjg.sjg_185_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/15/2023] Open
Affiliation(s)
- Mohmmed T. Sharip
- Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
| | - Sreedhar Subramanian
- Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
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17
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Wetwittayakhlang P, Tselekouni P, Al-Jabri R, Bessissow T, Lakatos PL. The Optimal Management of Inflammatory Bowel Disease in Patients with Cancer. J Clin Med 2023; 12:2432. [PMID: 36983432 PMCID: PMC10056442 DOI: 10.3390/jcm12062432] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/11/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern about the impact of IBD therapy on cancer risk and survival, as well as the effects of cancer therapies on the disease course of IBD. Managing IBD in patients with current or previous cancer is challenging since clinical guidelines are based mainly on expert consensus. Evidence is rare and mainly available from registries or observational studies. In contrast, excluding patients with previous/or active cancer from clinical trials and short-term follow-up can lead to an underestimation of the cancer or cancer recurrence risk of approved medications. The present narrative review aims to summarize the current evidence and provide practical guidance on the management of IBD patients with cancer.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand
| | - Paraskevi Tselekouni
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Reem Al-Jabri
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Peter L. Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- Department of Internal Medicine and Oncology, Semmelweis University, 1085 Budapest, Hungary
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18
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Stallhofer J, Guse J, Kesselmeier M, Grunert PC, Lange K, Stalmann R, Eckardt V, Stallmach A. Immunomodulator comedication promotes the reversal of anti-drug antibody-mediated loss of response to anti-TNF therapy in inflammatory bowel disease. Int J Colorectal Dis 2023; 38:54. [PMID: 36840779 PMCID: PMC9968255 DOI: 10.1007/s00384-023-04349-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/13/2023] [Indexed: 02/26/2023]
Abstract
PURPOSE Loss of therapeutic response (LOR) due to anti-drug antibodies (ADA) against tumor necrosis factor (TNF) inhibitors is common in patients with inflammatory bowel disease (IBD). We aimed to investigate whether immunomodulator comedication can reverse the immunogenic LOR to TNF inhibitors in IBD. METHODS In this real-world retrospective cohort study, 123 IBD patients with neutralizing ADA to infliximab or adalimumab and concomitant subtherapeutic trough levels were screened for clinical LOR. Subsequent ADA and trough level measurements and clinical outcomes were analyzed for patients who received either immunomodulator comedication or dose intensification of infliximab or adalimumab to overcome LOR. RESULTS Following immunogenic LOR, the initial anti-TNF regimen was optimized in 33 patients. In univariable and multivariable logistic regression analyses, immunomodulator comedication was identified as the crucial factor for regaining clinical remission and ADA clearance. Detectable trough levels (≥ 0.98 or ≥ 1.00 mg/L, respectively) had optimal predictive performance for both endpoints in receiver operating characteristics curves [area under the curve 0.86 (95% confidence interval 0.68-1.00) for regaining clinical remission, 0.87 (0.71-1.00) for ADA clearance]. Furthermore, 11/20 patients (55%) on a comedication with azathioprine or methotrexate and 2/13 patients (15%) receiving anti-TNF dose intensification exclusively (P = 0.032) exhibited ADA elimination, regain of therapeutic trough levels, and clinical remission. Regain of clinical remission alone was achieved in 17/20 (85%) patients receiving comedication and 2/13 (15%) patients receiving anti-TNF dose intensification (P = 1.6 × 10-4). CONCLUSION Immunogenic LOR to infliximab or adalimumab in IBD can be successfully reversed using immunomodulator comedication.
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Affiliation(s)
- Johannes Stallhofer
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany.
| | - Jan Guse
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany
| | - Miriam Kesselmeier
- Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany
| | - Philip Christian Grunert
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany
| | - Kathleen Lange
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany
| | - Robert Stalmann
- Institute of Clinical Chemistry and Laboratory Diagnostics, Centralized Diagnostic Laboratory Services, Jena University Hospital, Jena, Germany
| | - Verena Eckardt
- Institute of Clinical Chemistry and Laboratory Diagnostics, Centralized Diagnostic Laboratory Services, Jena University Hospital, Jena, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany
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19
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Poullenot F, Laharie D. Management of Inflammatory Bowel Disease in Patients with Current or Past Malignancy. Cancers (Basel) 2023; 15:cancers15041083. [PMID: 36831424 PMCID: PMC9954488 DOI: 10.3390/cancers15041083] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/02/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Immunomodulators, conventional immunosuppressants, and/or biologics are used more often, earlier, and longer than before in patients with inflammatory bowel disease (IBD). Along with this, the lifetime risk for cancer is estimated to be 33% in the general population in Europe. Thus, physicians face therapeutic choices in an increasing number of IBD patients with current or past malignancy. Few data are available so far for managing this IBD subpopulation and this clinical concern still remains a critical situation for four reasons: (i) risk of reactivation of dormant micrometastasis with immunomodulators is of major concern, (ii) there is a knowledge gap about the safety of the most recent molecules, (iii) current guidelines do not recommend the use of immunomodulators within 2-5 years after a diagnosis of cancer, (iv) patients with previous cancers are excluded from clinical trials. There is a lack of scientific evidence supporting the non-use of immunomodulators in IBD patients with previous cancer. Indeed, accumulative data suggest that the risk for recurrent and new cancer in patients with a history of cancer is not increased by thiopurines and anti-TNF agents. Most recently, cohort studies have found no differences in incident cancer rates in IBD patients with prior malignancy treated with vedolizumab or ustekinumab compared to those treated with anti-TNF agents. Therefore, decisions should be shared by the oncologist and the patient, considering the natural history of cancer, the time elapsed since cancer diagnosis, and IBD prognosis.
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Affiliation(s)
- Florian Poullenot
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-Gastroentérologie et Oncologie Digestive, Université de Bordeaux, F-33000 Bordeaux, France
| | - David Laharie
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-Gastroentérologie et Oncologie Digestive, Université de Bordeaux, F-33000 Bordeaux, France
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20
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Laredo V, García-Mateo S, Martínez-Domínguez SJ, López de la Cruz J, Gargallo-Puyuelo CJ, Gomollón F. Risk of Cancer in Patients with Inflammatory Bowel Diseases and Keys for Patient Management. Cancers (Basel) 2023; 15:871. [PMID: 36765829 PMCID: PMC9913122 DOI: 10.3390/cancers15030871] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 01/26/2023] [Accepted: 01/27/2023] [Indexed: 02/01/2023] Open
Abstract
Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.
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Affiliation(s)
- Viviana Laredo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Sandra García-Mateo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Samuel J. Martínez-Domínguez
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Julia López de la Cruz
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
| | - Carla J. Gargallo-Puyuelo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Fernando Gomollón
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
- CIBER for Liver and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
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21
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Therapeutic Management of Adults with Inflammatory Bowel Disease and Malignancies: A Clinical Challenge. Cancers (Basel) 2023; 15:cancers15020542. [PMID: 36672491 PMCID: PMC9856548 DOI: 10.3390/cancers15020542] [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: 12/13/2022] [Revised: 01/11/2023] [Accepted: 01/14/2023] [Indexed: 01/19/2023] Open
Abstract
Patients with chronic inflammatory bowel diseases (IBD) have increased risk of developing intestinal and extraintestinal cancers. However, once a diagnosis of malignancy is made, the therapeutic management of Crohn's disease (CD) and ulcerative colitis (UC) can be challenging as major guidelines suggest discontinuing the ongoing immunosuppressant and biological therapies for at least 2-5 years after the end of cancer treatment. Recently, new molecules such as vedolizumab and ustekinumab have been approved for IBD and limited data exist on the real risk of new or recurrent cancer in IBD patients with prior cancer, exposed to immunosuppressants and biologic agents. Thus, a multidisciplinary approach and case-by-case management is the preferred choice. The primary aim of our review was to summarize the current evidence about the safety of reintroducing an immunosuppressant or biologic agent in patients with a history of malignancy and to compare the different available therapies, including gut-selective agents. The secondary aim was to evaluate the clinical course of the IBD patients under cancer treatment who do not receive any specific immunosuppressant treatment after the diagnosis of cancer.
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22
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Sleiman J, Bassi M, Tsipotis E, Charabaty A. Medical Treatment Options for Ulcerative Colitis. Clin Colon Rectal Surg 2022; 35:428-436. [PMID: 36591395 PMCID: PMC9797279 DOI: 10.1055/s-0042-1758048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The landscape of management of ulcerative colitis, a type of inflammatory bowel disease, continues to change with advancement in pharmaceutical options as well as clinical treatment targets. Ulcerative colitis primarily involves the superficial layers of the large bowel, and cause active inflammation that can affect the colon from the rectum to the cecum in a relapsing and a remitting course. In this review, we provide evidence-based guidance on the selection of appropriate medical therapies based on individual patient and disease characteristics, with a focus on biologics and small molecules. We also review the role of surgery and management of acute severe ulcerative colitis.
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Affiliation(s)
- Joseph Sleiman
- Department of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Mehak Bassi
- Division of Gastroenterology and Hepatology, Saint Peter's University Hospital, Rutgers University, New Brunswick, New Jersey
| | - Evangelos Tsipotis
- Division of Gastroenterology and Hepatology, Augusta University, Augusta, Georgia
| | - Aline Charabaty
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland,Address for correspondence Aline Charabaty, MD Department of Gastroenterology, Johns Hopkins School of Medicine, Sibley Memorial Hospital5255 Loughboro Rd NW, Washington, DC, 20007
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Ustekinumab and Vedolizumab Are Equally Safe and Effective in Elderly Crohn's Disease Patients. Dig Dis Sci 2022; 68:1983-1994. [PMID: 36436155 PMCID: PMC9702964 DOI: 10.1007/s10620-022-07770-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/14/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Anti-tumour necrosis factor (anti-TNF) agents are associated with increased infection risk among elderly inflammatory bowel disease (IBD) patients, and thus, alternative biologics may be preferable. However, little comparative data exist on the safety and efficacy of vedolizumab and ustekinumab in elderly IBD patients. AIMS To compare the safety and effectiveness of ustekinumab and vedolizumab in elderly Crohn's disease patients. METHODS Patients ≥ 60 years old who commenced ustekinumab or vedolizumab for Crohn's disease (CD) were included. Primary outcome was serious infections, defined as requiring hospitalisation. Efficacy was assessed by treatment persistence and clinical response rates. We appropriately adjusted for confounders using propensity score-matched analysis weighted by the inverse predicted probability of treatment weighing and performed a logistic regression analysis to assess factors associated with serious infections and treatment persistence. RESULTS Eighty-three patients commencing ustekinumab and 42 commencing vedolizumab therapy were included. In a propensity adjusted cohort, the rate of serious infection and treatment persistence were comparable between ustekinumab and vedolizumab. There was a significant reduction in HBI at 6 and 12 months compared to baseline in both groups. Male gender was positively associated with serious infection risk at 12 months, and penetrating disease behaviour was positively associated with 12-month treatment persistence. Baseline HBI score was negatively associated with 12-month treatment persistence. Cox regression analysis showed no overall difference in treatment discontinuation-free and serious infection-free survival by 12 months. CONCLUSIONS We observed comparable safety and effectiveness for ustekinumab and vedolizumab in treating elderly CD patients.
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Fiske J, Liu E, Limdi JK, Conley TE, Townsend T, Davies M, Brockwell R, Baig D, Abdelbadiee S, Uney A, Liaros A, Gaba W, Smith PJ, Flanagan PK, Subramanian S. Safety and effectiveness of ustekinumab in elderly Crohn's disease patients. Eur J Gastroenterol Hepatol 2022; 34:1132-1139. [PMID: 36170682 DOI: 10.1097/meg.0000000000002436] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Anti-tumour necrosis factor (TNF) agents are associated with increased infection risk among elderly IBD patients, but little is known about non anti-TNF biologics in this cohort. We examined the safety and effectiveness of ustekinumab in elderly Crohn's patients. METHODS This retrospective multi-centre cohort study included Crohn's patients ≥60-years old who commenced ustekinumab. We recorded Harvey-Bradshaw index (HBI), concomitant steroid therapy, treatment persistence and new infections or malignancies. Primary outcome was serious infections requiring hospitalisation. RESULTS Seventy patients were included, with median age of 68 years. 43 (61.4%) had prior anti-TNF exposure, and 15 (21.4%) vedolizumab. Median treatment duration was 12 months, totalling 84 patient-years. Nine serious infections were reported, incidence 106.7/1000 patient-years. Systemic steroids were associated with increased risk of serious infections [odds ratio (OR) 7.83, 95% confidence interval (CI): 1.44-44.32, P = 0.02]. There were 27 "non-serious" infections; 321.4/1000 patient-years. Charlson co-morbidity index (OR 1.49, 95% CI: 1.05-2.12, P = 0.03) and steroid exposure (OR 44.10, 95% CI: 1.75-1112.10, P = 0.02) increased non-serious infection risk (P < 0.05). Mean HBI improved from 8.13 to 4.64 at 6 months and 4.10 at last follow up (P < 0.0001). 12-month treatment persistence was 55.7% (N = 39); 34 (48.6%) were steroid-free. CONCLUSION Ustekinumab was safe and effective in a cohort of elderly Crohn's disease patients. Infections were mostly mild, not resulting in therapy discontinuation. Serious infection risk was comparable to previously reported rates with anti-TNF agents. Steroid exposure was associated with an increased serious infection risk.
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Affiliation(s)
- Joseph Fiske
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Eleanor Liu
- Department of Gastroenterology, Pennine Acute Hospital NHS Trust
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospital NHS Trust
- Manchester Academic Health Sciences; Faculty of Medicine, Biology &Health, University of Manchester, Manchester
| | - Thomas E Conley
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Tristan Townsend
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Mike Davies
- Department of Gastroenterology, Arrowe Park Hospital, Wirral
| | | | - Daniyal Baig
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Sherif Abdelbadiee
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Anastasia Uney
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Angela Liaros
- Department of Gastroenterology, Whiston Hospital, Whiston
| | - Waqas Gaba
- Department of Gastroenterology, Warrington Hospital, Warrington
| | - Philip J Smith
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Paul K Flanagan
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
| | - Sreedhar Subramanian
- Department of Gastroenterology, Liverpool University Hospital NHS Foundation Trust, Liverpool
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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25
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Rezazadeh Ardabili A, Jeuring S, Mujagic Z, Oostenbrug L, Romberg‐Camps M, Jonkers D, van Bodegraven A, Pierik M. Classic drugs in the time of new drugs: real-world, long-term outcomes of thiopurine monotherapy in 1016 patients with inflammatory bowel disease. Aliment Pharmacol Ther 2022; 56:1030-1043. [PMID: 35794735 PMCID: PMC9544244 DOI: 10.1111/apt.17128] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/01/2022] [Accepted: 06/24/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Thiopurines remain recommended as maintenance therapy in patients with inflammatory bowel disease (IBD). Despite their widespread use, long-term effectiveness data are sparse and safety is an increasingly debated topic which thwarts proper delineation in the current IBD treatment algorithm. AIMS To document effectiveness and safety of thiopurine monotherapy in patients with IBD, using the population-based IBD South-Limburg (IBDSL) cohort METHODS: All patients starting thiopurine monotherapy as maintenance between 1991 and 2014 were included. Therapy was defined as effective if there was no escalation to biologicals, no course of corticosteroids, no surgery and no hospitalisation for active disease during treatment. Long-term effectiveness was assessed by adjusting for differences in follow-up using Kaplan-Meier analyses. Mid- to long-term safety regarding cancer incidence and clinically relevant liver disease was documented. RESULTS In total, 1016 patients (643 Crohn's disease [CD]; 373 ulcerative colitis [UC]) received thiopurine monotherapy at a median of 15.2 (Q1-Q3 4.2-48.5) months after diagnosis. During follow-up, effectiveness rates at 1, 5 and 10 years were 64%, 45%, 32%, respectively, in CD and and 66%, 41%, 36%, respectively in UC. No statistically significant differences in effectiveness were observed after stratification for era of initiation (pre-biological vs biological, CD: p = 0.56; UC: p = 0.43). Sixteen non-melanoma skin cancers (incidence rate [IR] 3.33/1000 PY), five lymphomas (IR 1.04/1000 PY) and one urinary tract cancer (IR 0.21/1000 PY) were recorded. Two cases of portal hypertension were identified. CONCLUSION In real-world practice, thiopurine monotherapy remains effective, safe and durable for patients with CD or UC, including in the era of biologics.
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Affiliation(s)
- Ashkan Rezazadeh Ardabili
- Department of Internal Medicine, Division of Gastroenterology and HepatologyMaastricht University Medical Centre+MaastrichtThe Netherlands
- School for Nutrition and Translational Research in Metabolism (NUTRIM)Maastricht University Medical Centre+MaastrichtThe Netherlands
| | - Steven Jeuring
- Department of Internal Medicine, Division of Gastroenterology and HepatologyMaastricht University Medical Centre+MaastrichtThe Netherlands
| | - Zlatan Mujagic
- Department of Internal Medicine, Division of Gastroenterology and HepatologyMaastricht University Medical Centre+MaastrichtThe Netherlands
- School for Nutrition and Translational Research in Metabolism (NUTRIM)Maastricht University Medical Centre+MaastrichtThe Netherlands
| | - Liekele Oostenbrug
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co‐MIK)Zuyderland Medical CentreSittard‐GeleenThe Netherlands
| | - Mariëlle Romberg‐Camps
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co‐MIK)Zuyderland Medical CentreSittard‐GeleenThe Netherlands
| | - Daisy Jonkers
- Department of Internal Medicine, Division of Gastroenterology and HepatologyMaastricht University Medical Centre+MaastrichtThe Netherlands
- School for Nutrition and Translational Research in Metabolism (NUTRIM)Maastricht University Medical Centre+MaastrichtThe Netherlands
| | - Adriaan van Bodegraven
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co‐MIK)Zuyderland Medical CentreSittard‐GeleenThe Netherlands
| | - Marieke Pierik
- Department of Internal Medicine, Division of Gastroenterology and HepatologyMaastricht University Medical Centre+MaastrichtThe Netherlands
- School for Nutrition and Translational Research in Metabolism (NUTRIM)Maastricht University Medical Centre+MaastrichtThe Netherlands
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Abstract
Inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. Individuals with IBD are at increased risk for several malignancies originating in the intestine, such as colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, and anal cancer. There are also several extraintestinal malignancies associated with IBD and IBD therapies, including cholangiocarcinoma, skin cancer, hematologic malignancies, genitourinary cancer, cervical cancer, and prostate cancer. The authors summarize the risk of cancer in patients with IBD, diagnosis and management of colorectal neoplasia in IBD, and management of patients with IBD and active or recent cancer.
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Affiliation(s)
- Adam S Faye
- Inflammatory Bowel Disease Center at NYU Langone Health, 305 East 33rd Street, Lower Level, New York, NY 10016, USA
| | - Ariela K Holmer
- Inflammatory Bowel Disease Center at NYU Langone Health, 305 East 33rd Street, Lower Level, New York, NY 10016, USA
| | - Jordan E Axelrad
- Inflammatory Bowel Disease Center at NYU Langone Health, 305 East 33rd Street, Lower Level, New York, NY 10016, USA.
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27
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Fries W, Demarzo MG, Navarra G, Viola A. Ulcerative Colitis in Adulthood and in Older Patients: Same Disease, Same Outcome, Same Risks? Drugs Aging 2022; 39:441-452. [PMID: 35641753 PMCID: PMC9155981 DOI: 10.1007/s40266-022-00943-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2022] [Indexed: 02/07/2023]
Abstract
The number of patients with inflammatory bowel disease (IBD) approaching an older age, together with the number of over-60-year-old patients newly diagnosed with IBD, is steadily increasing, reaching 25% of all patients. The present review focuses on late-onset ulcerative colitis (UC) and its initial disease course in comparison with that observed in younger adults in terms of extension at onset and the risk of proximal disease progression, medical treatment, surgery and hospitalization in the first years after diagnosis. We summarize the clues pointing to a milder disease course in a population which frequently presents major frailty due to comorbidities. With increasing age and thus increasing comorbidities, medical and surgical therapies frequently represent a challenge for treating physicians. The response, persistence, and risks of adverse events of conventional therapies indicated for late onset/older UC patients are examined, emphasizing the risks in this particular population, who are still being treated with prolonged corticosteroid therapy. Finally, we concentrate on data on biotechnological agents for which older patients were mostly excluded from pivotal trials. Real-life data from newer agents such as vedolizumab and ustekinumab show encouraging efficacy and safety profiles in the population of older UC patients.
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Affiliation(s)
- Walter Fries
- Gastroenterology and Chronic Bowel Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
| | - Maria Giulia Demarzo
- Gastroenterology and Chronic Bowel Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Giuseppe Navarra
- Oncologic Surgery, Department of Human Pathology of Adult and Evolutive Age, University of Messina, Messina, Italy
| | - Anna Viola
- Gastroenterology and Chronic Bowel Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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28
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Losurdo G, Gravina AG, Maroni L, Gabrieletto EM, Ianiro G, Ferrarese A. Future challenges in gastroenterology and hepatology, between innovations and unmet needs: A SIGE Young Editorial Board's perspective. Dig Liver Dis 2022; 54:583-597. [PMID: 34509394 DOI: 10.1016/j.dld.2021.08.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/09/2021] [Accepted: 08/12/2021] [Indexed: 02/08/2023]
Abstract
Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.
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Affiliation(s)
- Giuseppe Losurdo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro' of Bari; PhD Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University 'Aldo Moro' of Bari.
| | - Antonietta Gerarda Gravina
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Luca Maroni
- Department of Gastroenterology, Marche Polytechnic University, Ancona, Italy
| | | | - Gianluca Ianiro
- Digestive Disease Center, Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Alberto Ferrarese
- Gastroenterology and Hepatology, Azienda Ospedaliera Universitaria Integrata, Ospedale Borgo Trento, Verona, Italy
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29
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Lin H, Bai Z, Wu Q, Chu G, Zhang Y, Guo X, Qi X. Inflammatory Indexes for Assessing the Severity and Disease Progression of Ulcerative Colitis: A Single-Center Retrospective Study. Front Public Health 2022; 10:851295. [PMID: 35359771 PMCID: PMC8963422 DOI: 10.3389/fpubh.2022.851295] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 02/07/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Active and severe ulcerative colitis (UC) and non-response to 5-aminosalicylic acid (5-ASA) are related to poor outcomes and should be accurately identified. Several integrated inflammatory indexes are potentially useful to assess the disease severity in patients with acute or critical diseases but are underexplored in patients with UC. METHODS Patients with UC consecutively admitted to our hospital between January 2015 and December 2020 were retrospectively grouped according to the activity and severity of UC and response to 5-ASA. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), neutrophil-to-platelet ratio (NPR), platelet-to-albumin ratio (PAR), C-reactive protein-to-albumin ratio (CAR), and C-reactive protein-to-lymphocyte ratio (CLR) were calculated. The areas under receiver operating characteristic curves (AUC) were calculated. RESULTS Overall, 187 patients with UC were included, of whom 151 were active, 55 were severe, and 14 were unresponsive to 5-ASA. The active UC group had significantly higher NLR, PLR, SII, and PAR levels. SII had the greatest predictive accuracy for active UC, followed by PLR, PAR, and NLR (AUC = 0.647, 0.641, 0.634, and 0.626). The severe UC group had significantly higher NLR, PLR, SII, PAR, CAR, and CLR levels. CLR had the greatest predictive accuracy for severe UC, followed by CAR, PLR, SII, NLR, and PAR (AUC = 0.732, 0.714, 0.693, 0.669, 0.646, and 0.63). The non-response to the 5-ASA group had significantly higher CAR and CLR levels. CAR had a greater predictive accuracy for non-response to 5-ASA than CLR (AUC = 0.781 and 0.759). CONCLUSION SII, CLR, and CAR may be useful for assessing the severity and progression of UC, but remain not optimal.
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Affiliation(s)
- Hanyang Lin
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
| | - Zhaohui Bai
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China
| | - Qiong Wu
- Department of Thoracic Surgery, General Hospital of Northern Theater Command, Shenyang, China
| | - Guiyang Chu
- Information Section of Medical Security Center, General Hospital of Northern Theater Command, Shenyang, China
| | - Yongguo Zhang
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Postgraduate College, China Medical University, Shenyang, China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China
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30
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Venner JM, Bernstein CN. Immunomodulators: still having a role? Gastroenterol Rep (Oxf) 2022; 10:goac061. [PMID: 36381225 PMCID: PMC9642324 DOI: 10.1093/gastro/goac061] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/08/2022] [Accepted: 10/09/2022] [Indexed: 11/09/2022] Open
Abstract
Immunomodulators, particularly the thiopurines and to a lesser extent methotrexate, were standard of care for inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, for >40 years. While there has been a renaissance in available therapies with the advent of biologics and small molecules, an impetus remains for the ongoing use of thiopurines and methotrexate. This is particularly true for the maintenance of remission and when used in combination therapy with infliximab to suppress anti-biologic antibodies. This article summarizes the data behind immunomodulator use in Crohn’s disease, focusing on the beneficial role these drugs still have while acknowledging their clinical limitations.
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Affiliation(s)
- Jeffery M Venner
- University of Manitoba IBD Clinical and Research Centre , Winnipeg, Manitoba, Canada
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba , Winnipeg, Manitoba, Canada
| | - Charles N Bernstein
- University of Manitoba IBD Clinical and Research Centre , Winnipeg, Manitoba, Canada
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba , Winnipeg, Manitoba, Canada
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31
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Zhang H, Zhang M, Chen X, Guo M, Zhou R, Lv H, Li Y, Tan B, Li J, Xu H, Zheng W, Yang H, Qian J. Risk of malignancy in patients with inflammatory bowel disease: a population-based cohort study from China. Int J Cancer 2022; 150:1770-1778. [PMID: 35037241 DOI: 10.1002/ijc.33932] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 12/15/2021] [Accepted: 12/22/2021] [Indexed: 11/11/2022]
Abstract
Carcinogenesis is one of major complications for patients with inflammatory bowel disease (IBD) and causes poor prognosis. We aimed to describe cancer incidence in Chinese IBD cohort compared with general population-based cancer registration data and further explore associated risk factors for cancer occurrence in IBD patients. IBD inpatients from January 1998 to January 2018 were included in this study. Patients were followed up from date of IBD diagnosis until either the date of first cancer diagnosis or January 2019. Standardized incidence ratios (SIRs) of overall cancer and site-specific cancers were calculated. A total of 869 UC and 516 CD patients were finally included with median follow-up time of 7 and 5 years respectively. 53 cases developed malignancies. After standardization by age and gender, standardized incidence ratio (SIR) of total cancer occurrence in IBD patients was 1.77 (95%CI, 1.33-2.32). As for UC, digestive cancers (SIR 3.75; 95%CI, 2.29-5.80), thyroid cancer (SIR 10.34; 95%CI, 4.72-19.64) and hematological malignancies (SIR 6.25; 95%CI, 1.68-16.00) had the highest incidence, which were prominent in young and middle-aged patients. Use of steroids, immunosuppressants or infliximab did not present higher risk of malignancies in UC patients. There were no significant difference in cancer risk between CD patients and general population. In conclusion, the increased risks of multiple cancers are particularly prominent in Chinese UC patients and these findings can provide more targeted guidance for cancer monitoring in Chinese IBD patients.
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Affiliation(s)
- Huimin Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mengmeng Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuanfu Chen
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingyue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Runing Zhou
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Lv
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bei Tan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hui Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiyang Zheng
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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32
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Singh A, Mahajan R, Kedia S, Dutta AK, Anand A, Bernstein CN, Desai D, Pai CG, Makharia G, Tevethia HV, Mak JWY, Kaur K, Peddi K, Ranjan MK, Arkkila P, Kochhar R, Banerjee R, Sinha SK, Ng SC, Hanauer S, Verma S, Dutta U, Midha V, Mehta V, Ahuja V, Sood A. Use of thiopurines in inflammatory bowel disease: an update. Intest Res 2022; 20:11-30. [PMID: 33845546 PMCID: PMC8831775 DOI: 10.5217/ir.2020.00155] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 02/19/2021] [Accepted: 03/01/2021] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College, Vellore, India
| | - Abhinav Anand
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Charles N. Bernstein
- University of Manitoba IBD Clinical and Research Centre, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Devendra Desai
- P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - C. Ganesh Pai
- Department of Gastroenterology, Kasturba Medical College, Manipal, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | | | - Joyce WY Mak
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Kiran Peddi
- Citizens Centre for Digestive Disorders, Hyderabad, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Perttu Arkkila
- Department of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland
| | - Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rupa Banerjee
- Asian Institute of Gastroenterology Hyderabad, Hyderabad, India
| | - Saroj Kant Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Stephen Hanauer
- Department of Medicine, Northwestern University, Chicago, IL, USA
| | - Suhang Verma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
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33
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Choi Y, Kim N. Inflammatory Bowel Diseases. SEX/GENDER-SPECIFIC MEDICINE IN THE GASTROINTESTINAL DISEASES 2022:281-299. [DOI: 10.1007/978-981-19-0120-1_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Mala A, Foteinogiannopoulou K, Koutroubakis IE. Solid extraintestinal malignancies in patients with inflammatory bowel disease. World J Gastrointest Oncol 2021; 13:1956-1980. [PMID: 35070035 PMCID: PMC8713323 DOI: 10.4251/wjgo.v13.i12.1956] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/06/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
Malignancies constitute the second cause of death in patients with inflammatory bowel diseases (IBD), after cardiovascular diseases. Although it has been postulated that IBD patients are at greater risk of colorectal cancer compared to the general population, lately there has been evidence supporting that this risk is diminishing over time as a result of better surveillance, while the incidence of extraintestinal cancers (EICs) is increasing. This could be attributed either to systemic inflammation caused by IBD or to long-lasting immunosuppression due to IBD treatments. It seems that the overall risk of EICs is higher for Crohn’s disease patients and it is mainly driven by skin cancers, and liver-biliary cancers in patients with IBD and primary sclerosing cholangitis. The aims of this review were first to evaluate the prevalence, characteristics, and risk factors of EICs in patients with IBD and second to raise awareness regarding a proper surveillance program resulting in early diagnosis, better prognosis and survival, especially in the era of new IBD treatments that are on the way.
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Affiliation(s)
- Anastasia Mala
- Department of Medical Oncology, University Hospital of Heraklion, Heraklion 71110, Crete, Greece
| | | | - Ioannis E Koutroubakis
- Department of Gastroenterology, University Hospital of Heraklion, Heraklion 71110, Crete, Greece
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35
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Adamek HE, Hommelsheim A. [Intestinal and extraintestinal malignancies in inflammatory bowel disease: case series from a tertiary center]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 60:320-325. [PMID: 34820805 DOI: 10.1055/a-1672-4861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Inflammatory bowel diseases have recorded increasing incidence. A long period of illness and immunsuppressive drugs run a high risk of complications, this is particularly true for neoplasias.Medical records of patients with inflammatory bowel diseases who developed a malignant disease during 2000 and 2020 were used for analysis.51 patients could be included. 56% of tumors were located extraintestinal and occurred more often in patient with Crohn's disease. Neoplasias were more frequent in men (61 %).Individual prevention recommendations are urgently needed. Our focus should be extended to extraintestinal neoplasias. Initial diagnosis is often made in the 50+ age group. Thus, standardizised prevention programs including life-style factors should be started at the time of IBD diagnosis.
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36
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Nguyen ALH, Sparrow MP. Evolving Role of Thiopurines in Inflammatory Bowel Disease in the Era of Biologics and New Small Molecules. Dig Dis Sci 2021; 66:3250-3262. [PMID: 33073334 DOI: 10.1007/s10620-020-06662-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Accepted: 10/06/2020] [Indexed: 12/09/2022]
Abstract
In recent years, with the increasing availability of biologic therapies and due to safety concerns, the role of thiopurines in the management of inflammatory bowel disease has been questioned. While acknowledging that the benefit/risk ratio of biologic therapies is very high, they are expensive and are not required by a majority of patients. Therefore, thiopurines do retain an important role as steroid-sparing and maintenance agents when used as monotherapy, and in combination therapy with biologics due to their clinical and pharmacokinetic optimization of anti-tumor necrosis factor agents in particular. Safety concerns with thiopurines are real but also relatively rare, and with careful pre-treatment screening and ongoing monitoring thiopurine benefits outweigh risks in the majority of appropriately selected patients. Measurement of newer pharmacogenomic markers such as nudix hydrolase 15 (NUDT15), when combined with knowledge of existing known mutations (e.g., thiopurine S-methyltransferase-TPMT), will hopefully minimize the risk of potentially life-threatening leukopenia by allowing for pre-treatment dosing stratification. Further optimization of thiopurine dosing via measurement of thiopurine metabolites should be performed routinely and is superior to weight-based dosing. The association of thiopurines with malignancies including lymphoproliferative disorders needs to be recognized in all patients and individualized in each patient. The decrease in lymphoma risk after thiopurine cessation provides an incentive for thiopurine de-escalation in appropriate patients after a period of prolonged deep remission. This review will summarize the current role of thiopurines in inflammatory bowel disease management and provide recommendations for commencing and monitoring therapy, and when to consider de-escalation.
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Affiliation(s)
- Anke L H Nguyen
- Department of Gastroenterology, Alfred Health, 55 Commercial Road, Melbourne, 3004, VIC, Australia.,Monash University, Melbourne, Australia
| | - Miles P Sparrow
- Department of Gastroenterology, Alfred Health, 55 Commercial Road, Melbourne, 3004, VIC, Australia. .,Monash University, Melbourne, Australia.
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37
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Greuter T, Vavricka S, König AO, Beaugerie L, Scharl M. Malignancies in Inflammatory Bowel Disease. Digestion 2021; 101 Suppl 1:136-145. [PMID: 32799195 DOI: 10.1159/000509544] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 05/11/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to, the gut. Association between IBD and cancer has been clearly established and is uniformly accepted. SUMMARY IBD patients are at particular risk for intestinal and extraintestinal cancers. There are 2 underlying mechanisms: (1) IBD-related inflammation triggers initiation and progression of tumor formation. This particularly results in the development of colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, anal cancer, and cholangiocarcinoma. (2) Immunosuppressive drugs exhibit carcinogenic properties such as shown for azathioprine and anti-TNF promoting lymphoproliferative malignancies and melanoma and nonmelanoma skin cancer. However, within the last years, IBD-related cancer incidence and prevalence have been decreasing, which might be attributed to better treatment options and surveillance strategies. Moreover, novel biological drugs have been introduced in clinical practice and have dramatically changed long-term IBD management. Therefore, we sought to summarize up-to-date knowledge about (1) overall cancer risk; (2) risk and protective factors for cancer development; and (3) inflammation- and immunosuppression-related malignancies in the current anti-TNF era of IBD. Key Messages: Recent studies and meta-analyses questioned the excess rates of cancer in IBD patients. However, IBD still is associated with cancer development due to ongoing intestinal inflammation and the use of potential carcinogenic drugs. Patients should be educated about the increased risk of cancer with IBD and IBD drugs. However, they should also be informed that most malignancy subtypes are possibly preventable by controlling intestinal inflammation and by using adequate screening strategies.
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Affiliation(s)
- Thomas Greuter
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland, .,Department of Internal Medicine, GZO - Zurich Regional Health Center, Wetzikon, Switzerland,
| | - Stephan Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.,Center for Gastroenterology and Hepatology, Zurich, Switzerland
| | - Alexander O König
- Department of Gastroenterology and Hepatology, University of Göttingen, Göttingen, Germany
| | - Laurent Beaugerie
- Department of Gastroenterology, Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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38
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Bakulin IG, Skalinskaya MI, Maev IV, Skazyvaeva EV, Zhuravleva MS, Gaikovaya LB, Bakulina NV, Ermakov AI, Alekseenko ES, Ivanova KN, Solovev MV. Pharmacotherapy of inflammatory bowel diseases: efficacy performance and safety management. TERAPEVT ARKH 2021; 93:841-852. [DOI: 10.26442/00403660.2021.08.200982] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 08/30/2021] [Indexed: 12/30/2022]
Abstract
Treatment of inflammatory bowel diseases IBD (Crohns disease, ulcerative colitis) is aimed at achieving clinical, endoscopic and histological remission, minimizing surgical complications, and ensuring a normal quality of life. However, the use of medical treatment is potentially associated with various adverse events, among which infectious complications, malignant neoplasms, as well as myelotoxicity, hepatotoxicity, skin lesions and others. The risk of side effects depends on the type of drug therapy (5-aminosalicylates, thiopurines, biologicals, etc.), the duration of treatment, the presence of extra-intestinal manifestations, etc. The article provides an overview of data on both the effectiveness and frequency of various side effects of the main classes of drugs in IBD, presents methods of investigation which can predict the effectiveness and development of side effects, the implementation of which can be considered as a variant of personalized therapy in IBD.
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39
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Zhu M, Ran Z. Clinical characteristics of ulcerative colitis in elderly patients. JGH Open 2021; 5:849-854. [PMID: 34386591 PMCID: PMC8341179 DOI: 10.1002/jgh3.12612] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 06/27/2021] [Accepted: 07/01/2021] [Indexed: 12/18/2022]
Abstract
The incidence of ulcerative colitis (UC) in elderly patients is increasing. Elderly UC patients are likely to exhibit distinct features both at diagnosis and during follow-up. Age-related problems, including complications, immune dysfunction, and multidrug use, make the diagnosis and treatment of elderly UC more challenging. Suboptimal treatment considering adverse events leads to poor clinical outcome in elderly UC patients. Here, we reviewed the epidemiology, clinical presentation, medical therapy, colorectal cancer surveillance of UC in elderly patients.
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Affiliation(s)
- Mingming Zhu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of MedicineShanghai Jiao Tong University, Shanghai Jiao Tong University; Shanghai Institute of Digestive DiseaseShanghaiChina
| | - Zhihua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of MedicineShanghai Jiao Tong University, Shanghai Jiao Tong University; Shanghai Institute of Digestive DiseaseShanghaiChina
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40
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Caviglia GP, Martini G, Armandi A, Rosso C, Vernero M, Bugianesi E, Astegiano M, Saracco GM, Ribaldone DG. Risk Factors of Urothelial Cancer in Inflammatory Bowel Disease. J Clin Med 2021; 10:3257. [PMID: 34362041 PMCID: PMC8347965 DOI: 10.3390/jcm10153257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 07/22/2021] [Accepted: 07/22/2021] [Indexed: 01/31/2023] Open
Abstract
Extraintestinal cancers are important complications in patients with inflammatory bowel disease (IBD). A limited number of publications are available regarding the association between IBD and urothelial cancer. The primary outcome of our study was the comparison of the prevalence of urothelial cancer in patients with IBD with respect to the prevalence in the general population. Secondary outcomes were the assessment of risk factors for the onset of urothelial cancer in IBD. In a retrospective study we examined the medical records of all patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2021. For each of the patients with identified urothelial cancer, more than ten patients without cancer were analyzed. Furthermore, 5739 patients with IBD were analyzed and 24 patients diagnosed with urothelial cancer were identified. The incidence of urothelial cancer, compared with the incidence in the general population, was not significantly different (0.42% vs. 0.42%; p = 0.98). Twenty-three cases were then compared (1 case was discarded due to lack of follow-up data) against 250 controls. During the multivariate analysis, smoking (odds ratio, OR = 8.15; 95% confidence interval, CI = 1.76-37.63; p = 0.007) and male sex (OR = 4.04; 95% CI = 1.29-12.66; p = 0.016) were found as risk factors. In conclusion, patients with IBD have a similar risk of developing urothelial cancer compared to the general population, but males with a history of smoking are at increased risk.
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Affiliation(s)
- Gian Paolo Caviglia
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Giorgio Martini
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Angelo Armandi
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Chiara Rosso
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Marta Vernero
- Department of Internal Medicine, San Matteo Hospital, 27100 Pavia, Italy;
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Marco Astegiano
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy;
| | - Giorgio Maria Saracco
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
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41
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Gargallo-Puyuelo CJ, Laredo V, Gomollón F. Thiopurines in Inflammatory Bowel Disease. How to Optimize Thiopurines in the Biologic Era? Front Med (Lausanne) 2021; 8:681907. [PMID: 34336887 PMCID: PMC8322650 DOI: 10.3389/fmed.2021.681907] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 06/23/2021] [Indexed: 12/18/2022] Open
Abstract
Thiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed.
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Affiliation(s)
| | - Viviana Laredo
- Department of Gastroenterology, University Clinic Hospital Lozano Blesa, Zaragoza, Spain
| | - Fernando Gomollón
- Department of Gastroenterology, University Clinic Hospital Lozano Blesa, Zaragoza, Spain.,Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Zaragoza, Spain.,Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain.,Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas, Madrid, Spain
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42
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Sipponen T, Af Björkesten CG, Hallinen T, Ilus T, Soini E, Eberl A, Heikura M, Kellokumpu M, Koskela R, Nielsen C, Nuutinen H, Heikkinen M, Suhonen UM, Tillonen J, Wennerström ECM, Borsi A, Koivunen MR. A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn's disease patients in Finland. Scand J Gastroenterol 2021; 56:661-670. [PMID: 33820465 DOI: 10.1080/00365521.2021.1906315] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland. METHODS Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability. RESULTS Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period. CONCLUSIONS Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification. TRIAL REGISTRATION EUPAS30920.
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Affiliation(s)
- Taina Sipponen
- Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | | | | | - Tuire Ilus
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | | | - Anja Eberl
- Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Mikko Heikura
- Department of Gastroenterology, North Karelia Central Hospital, Joensuu, Finland
| | - Mikko Kellokumpu
- Department of Internal Medicine, Lapland Central Hospital, Rovaniemi, Finland
| | - Ritva Koskela
- Department of Medicine, Division of Gastroenterology, Oulu University Hospital, Oulu, Finland
| | - Christian Nielsen
- Department of Internal Medicine, Vaasa Central Hospital, Vaasa, Finland
| | - Heikki Nuutinen
- Division of Gastroenterology, Department of Medicine, Turku University Hospital, Turku, Finland
| | - Markku Heikkinen
- Department of Internal Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Ulla-Maija Suhonen
- Department of Internal Medicine, Kainuu Central Hospital, Kajaani, Finland
| | - Jyrki Tillonen
- Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
| | - E Christina M Wennerström
- Medical Affairs, Janssen Cilag AB, Solna, Sweden.,Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | - Andras Borsi
- Janssen Cilag Limited, EMEA HEMAR, High Wycombe, United Kingdom
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Geng Z, Geng Q. Risk of Urinary Bladder Cancer in Patients With Inflammatory Bowel Diseases: A Meta-Analysis. Front Surg 2021; 8:636791. [PMID: 34124132 PMCID: PMC8188732 DOI: 10.3389/fsurg.2021.636791] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 03/26/2021] [Indexed: 12/24/2022] Open
Abstract
A systematic search of the PubMed, Cochrane, Embase, and Web of Science databases was conducted to investigate the risk of urinary bladder cancer (BC) in patients with inflammatory bowel disease (IBD). We identified 168 articles, of which 11 met the inclusion and exclusion criteria. Our analysis included 165,176 patients with IBD, 491 of whom had BC. Overall, the pooled standardized incidence ratio (SIR) was 0.99 (95% CI: 0.87–1.12; I2 = 0%). Further subgroup analysis showed that BC risk was neither statistically higher for Crohn's disease (CD) (SIR: 1.19; 95% CI: 0.94–1.44; I2 = 0%) nor for patients with ulcerative colitis (UC) (SIR: 0.92; 95% CI: 0.77–1.06; I2 = 0%). In the analysis of two case-control studies providing data on BC in UC and CD combined, IBD patients seemed to have a higher risk of BC than non-IBD patients (relative risk: 1.25; 95% CI: 0.77–2.03; I2 = 37.5%). Although the overall risk of BC was not significantly increased among patients with IBD, there was a weak trend for the risk to be elevated in CD patients, indicating marginal significance. These findings may primarily be explained by the opposite effects of smoking on CD and UC as well as the immunosuppressive drugs these patients often take.
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Affiliation(s)
- Zhihua Geng
- Department of Orthopedics of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qing Geng
- Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
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44
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Kim SE. [How Should We Do Different Approach to Treat Inflammatory Bowel Disease by Gender Difference?]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 77:241-247. [PMID: 34035202 DOI: 10.4166/kjg.2021.064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/20/2021] [Accepted: 05/21/2021] [Indexed: 11/03/2022]
Abstract
Although not as prominent, there are gender/sex differences in incidence/prevalence, clinical manifestation and disease course, comorbidities, therapeutic response, and patients coping strategy to the disease of inflammatory bowel disease (IBD). In this review, current knowledge about gender-specific differences in IBD would be provided and how to apply this in clinical practice be discussed.
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Affiliation(s)
- Seong-Eun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
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45
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Feng D, Yang Y, Wang Z, Wei W, Li L. Inflammatory bowel disease and risk of urinary cancers: a systematic review and pooled analysis of population-based studies. Transl Androl Urol 2021; 10:1332-1341. [PMID: 33850767 PMCID: PMC8039624 DOI: 10.21037/tau-20-1358] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background The aim of this study is to elucidate the risk of urologic cancers in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Methods Electronic databases including PubMed, the Cochrane Library, Embase and Web of Science, and manual retrieval were conducted from inception to June 2020. Two reviewers independently searched the above databases and selected the studies using prespecified standardized criteria. The Newcastle-Ottawa Scale was used to assess the risk of bias in the included studies, and this meta-analysis was completed by STATA version 14.2. Results A total of 12 cohort studies and 4 case-control studies were included in this meta-analysis. Overall, patients with inflammatory bowel disease (IBD) were at significantly increased risk of renal cancer (RCa) [standardized incidence ratio (SIR): 1.53; 95% confidence interval (CI): 1.25–1.80; I2=42.4%], but not at increased risk of prostate cancer (PCa), bladder cancer (BCa) and male genital cancer. In the subgroup analysis, CD patients had a significantly higher RCa risk (SIR: 1.95; 95% CI: 1.45–2.44; I2=39.9%). Besides, CD patients seemed to be at borderline significantly increased risks of PCa (SIR: 1.07; 95% CI: 0.93–1.20; I2=15.1%) and BCa (SIR:1.19; 95% CI: 0.94–1.44; I2=0%), and UC patients seemed to be at borderline significantly increased risks of RCa (SIR:1.31; 95% CI: 0.94–1.67; I2=48.0%) and PCa (SIR: 1.13; 95% CI: 0.93–1.33; I2=73.5%). Notably, we observed that IBD patients in Eastern countries have significantly increased PCa risk (SIR: 2.66; 95% CI: 1.52–3.81; I2=13.6%), especially for UC patients (SIR: 3.01; 95% CI: 1.75–4.27; I2=0.0%). Conclusions Our findings indicate that IBD patients with special reference to CD patients increase the risk of RCa. Besides, IBD patients in Asian countries have significantly increased risk of PCa, especially for UC patients. Further studies are warranted to elucidate the potential mechanism of RCa associated with IBD and the differences of the risk of urinary cancers between Eastern and Western countries.
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Affiliation(s)
- Dechao Feng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Yubo Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhenghao Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Wuran Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Li Li
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.,Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
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Zhang C, Liu S, Peng L, Wu J, Zeng X, Lu Y, Shen H, Luo D. Does inflammatory bowel disease increase the risk of lower urinary tract tumors: a meta-analysis. Transl Androl Urol 2021; 10:164-173. [PMID: 33532306 PMCID: PMC7844520 DOI: 10.21037/tau-20-1020] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is characterized by chronic inflammation that could be a risk factor for extraintestinal cancer. The aim of this study is to evaluate whether inflammatory bowel disease is related to the risk of lower urinary tract tumors. Methods A systematical research was performed on various medical databases including PubMed, the Cochrane Library, Embase and Web of Science from inception to April 2020. Data were independently extracted by two reviewers. The Newcastle-Ottawa Scale and the Oxford Centre for Evidence-Based Medicine criteria were used to assess the quality of included articles. The analysis was completed by STATA version 14.2. Results Six hundred and twelve of records were initially identified and 16 studies were included in the final analysis. In general, inflammatory bowel disease patients were not at increased risk of prostate cancer, bladder cancer and male genital cancer. In the subgroup analysis, Crohn’s disease patients seemed to have borderline increased risk of prostate cancer [standardized incidence ratio: 1.05; 95% confidence interval (CI): 0.90–1.21; I2=15.1%] and bladder cancer (standardized incidence ratio: 1.19; 95% CI: 0.94–1.44; I2=0.0%), and ulcerative colitis patients seemed to have borderline increased risk of prostate cancer (standardized incidence ratio: 1.13; 95% CI: 0.93–1.33; I2=73.5%). Conclusions Inflammatory bowel disease did not significantly increase the risk of prostate cancer, bladder cancer and male genital cancer. Crohn’s disease patients seemed to have a higher risk of prostate cancer and bladder cancer, and ulcerative colitis patients seemed to have a higher risk of prostate cancer. ulcerative colitis patients in East Asian countries have significantly increased prostate cancer risk.
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Affiliation(s)
- Chi Zhang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Shengzhuo Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Liao Peng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Jiapei Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao Zeng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yiping Lu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Shen
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Deyi Luo
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
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Matsumoto S, Mashima H. Real-World Long-Term Remission Maintenance for 10 Years With Thiopurines in Ulcerative Colitis. CROHN'S & COLITIS 360 2021; 3:otab003. [PMID: 36777065 PMCID: PMC9802170 DOI: 10.1093/crocol/otab003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND To evaluate the therapeutic outcomes and long-term prognosis of patients receiving remission maintenance therapy using thiopurines for ulcerative colitis (UC). METHODS Of 193 biologic-naive patients with UC who began thiopurine therapy at our hospital between 2000 and 2019, 161 patients were included after the exclusion of 32 patients who were intolerant to thiopurines and discontinued the drugs within 3 months. Short- and long-term clinical outcomes were retrospectively analyzed. Subsequently, the patients were divided into 2 groups (exacerbation and nonexacerbation groups) and clinical outcomes were analyzed and compared. Multivariate analysis was performed to identify risk factors for UC exacerbation. Finally, adverse events observed in 193 patients were examined. RESULTS Clinical remission rates at 2 months, 6 months, and 1 year after the start of thiopurine therapy were 50.0%, 58.0%, and 63.9%, respectively. At 1, 2, 5, and 10 years, the cumulative event-free rates were 77.6%, 60.8%, 48.5%, and 42.2%, respectively; the cumulative UC exacerbation rates were 17.0%, 32.5%, 42.2%, and 43.7%, respectively; and the cumulative colectomy rates were 0.6%, 1.3%, 8.5%, and 10.7%, respectively. Prior use of steroids (dose ≥40 mg/d) was a significant risk factor for UC exacerbation during remission maintenance therapy with thiopurines (hazard ratio, 2.26; 95% confidence interval, 1.18-4.34; P = 0.014). Adverse reactions occurred in 42 patients (21.8%; 46 events). Concurrent diseases were observed in 18 patients (9.3%). CONCLUSIONS Thiopurines were effective for long-term maintenance of remission in steroid-dependent/refractory UC. Their effect weakened in only a few patients continuously treated with them for 4 years or longer.
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Affiliation(s)
- Satohiro Matsumoto
- Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, Saitama, Saitama, Japan
| | - Hirosato Mashima
- Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, Saitama, Saitama, Japan
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Goodman WA, Erkkila IP, Pizarro TT. Sex matters: impact on pathogenesis, presentation and treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2020; 17:740-754. [PMID: 32901108 PMCID: PMC7750031 DOI: 10.1038/s41575-020-0354-0] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/27/2020] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD), as do most chronic inflammatory disorders, displays unique features and confers different risk factors in male and female patients. Importantly, sex-based differences in IBD exist for epidemiological incidence and prevalence among different age groups, with men and women developing distinct clinical symptoms and disparity in severity of disease. In addition, the presentation of comorbidities in IBD displays strong sex differences. Notably, particular issues exclusive to women's health, including pregnancy and childbirth, require specific considerations in female patients with IBD of childbearing age that can have a substantial influence on clinical outcomes. This Review summarizes the latest findings regarding sex-based differences in the epidemiology, clinical course, comorbidities and response to current therapies in patients with IBD. Importantly, the latest basic science discoveries in this area of investigation are evaluated to provide insight into potential mechanisms underlying the influence of sex on disease pathogenesis, as well as to design more personalized and efficacious care, in patients with IBD.
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Affiliation(s)
- Wendy A Goodman
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Ian P Erkkila
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Theresa T Pizarro
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
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Feng D, Bai Y, Liu S, Yang Y, Han P, Wei W. Risk of renal cancer in patients with inflammatory bowel disease: A pooled analysis of population-based studies. Urol Oncol 2020; 39:93-99. [PMID: 33214029 DOI: 10.1016/j.urolonc.2020.10.078] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 08/14/2020] [Accepted: 10/30/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Currently, newer epidemiological studies report the association between inflammatory bowel disease (IBD) and risk of renal cancer (RCa). Thus, we conducted a meta-analysis to determine whether IBD patients were associated with RCa risk. METHODS Various medical databases were searched from inception to April 2020. Standardized incidence ratio (SIR) or relative risk (RR) with corresponding 95% confidence intervals (CIs) were pooled. The meta-analysis was completed by STATA version 14.2. RESULTS A total of 421 articles were identified, and 11 studies met the inclusion criteria. Data from 9 cohort studies showed a significantly increased risk of RCa in IBD patients (pooled SIR: 1.53; 95%CI: 1.25-1.80; I2 = 42.4%), especially for patients with Crohn's disease (CD) (pooled SIR: 1.95; 95%CI: 1.45-2.44; I2 = 39.9%). We did not observe a significantly increased risk of RCa in patients with ulcerative colitis (UC) (pooled SIR: 1.31; 95%CI: 0.94-1.67; I2 = 48.0%) when compared to the background population. Only 2 case-control studies reported the results of RCa risk, showing no significant difference between IBD group and IBD-free group (pooled RR: 1.64; 95%CI: 0.52-5.22; I2 = 77.9%). CONCLUSIONS Our findings indicate that IBD patients with special reference to CD patients have a significantly higher risk of RCa. Further studies are warranted to enable definite conclusions to be drawn.
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Affiliation(s)
- Dechao Feng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yunjin Bai
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Shengzhuo Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yubo Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Ping Han
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Wuran Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
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Zheng KYC, Guo CG, Wong IOL, Chen L, Chung HY, Cheung KS, Leung WK. Risk of malignancies in patients with inflammatory bowel disease who used thiopurines as compared with other indications: a territory-wide study. Therap Adv Gastroenterol 2020; 13:1756284820967275. [PMID: 33281936 PMCID: PMC7682226 DOI: 10.1177/1756284820967275] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 09/28/2020] [Indexed: 02/04/2023] Open
Abstract
AIMS Thiopurines are believed to increase cancer risks, but data from Asian patients are sparse. We determined the risks of malignancies in thiopurine users with inflammatory bowel disease (IBD) or other indications from Hong Kong. METHODS All patients who had received thiopurines between 2005 and 2009 in Hong Kong were identified from local electronic healthcare database. Patients were followed from the start date of thiopurines until death or end of study in 2017. We excluded patients with baseline malignancy. Standardized incidence ratios (SIR) and the corresponding 95% confidence intervals (CI) of all malignancies were computed against matched local general population from the cancer registry. Patients in the same diagnosis category but not exposed to thiopurines were included as controls. RESULTS There were 7452 thiopurines users (median age 47.0 years), including 595 IBD patients, with a median follow-up of 11.2 years. Of them, 684 (9.2%) developed malignancies with an overall SIR of 2.30 (95% CI 2.13-2.48). The SIR in IBD patients who used thiopurines was 2.37 (95% CI 1.71-3.18) as compared with non-users (SIR 1.35, 95% CI 1.05-1.72). Highest risk of malignancies was observed in post-transplant patients (SIR 3.83, 95% CI 3.34-4.35), and lower risks were seen in patients with rheumatological diseases (SIR 1.46, 95% CI 1.02-2.02). CONCLUSION IBD patients in Hong Kong who used thiopurines had 2.37-fold increase in risk of malignancies than the general population, which was higher than non-users and different from thiopurine users for other indications.
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Affiliation(s)
- Kelvin Y. C. Zheng
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Chuan-Guo Guo
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Irene O. L. Wong
- School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Lijia Chen
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Ho Yin Chung
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Ka Shing Cheung
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
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