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1
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Grillo TG, Silveira CFDSMP, Quaglio AEV, Dutra RDM, Baima JP, Bazan SGZ, Sassaki LY. Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease: A review of the literature. World J Cardiol 2023; 15:217-228. [PMID: 37274378 PMCID: PMC10237008 DOI: 10.4330/wjc.v15.i5.217] [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: 01/16/2023] [Revised: 02/09/2023] [Accepted: 04/12/2023] [Indexed: 05/19/2023] Open
Abstract
Tumor necrosis factor inhibitors (anti-TNFs) are widely used therapies for the treatment of inflammatory bowel diseases (IBD); however, their administration is not risk-free. Heart failure (HF), although rare, is a potential adverse event related to administration of these medications. However, the exact mechanism of development of HF remains obscure. TNFα is found in both healthy and damaged hearts. Its effects are concentration- and receptor-dependent, promoting either cardio-protection or cardiomyocyte apoptosis. Experimental rat models with TNFα receptor knockout showed increased survival rates, less reactive oxygen species formation, and improved diastolic left ventricle pressure. However, clinical trials employing anti-TNF therapy to treat HF had disappointing results, suggesting abolishment of the cardioprotective properties of TNFα, making cardiomyocytes susceptible to apoptosis and oxidation. Thus, patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy. This review aims to discuss adverse events associated with the administration of anti-TNF therapy, with a focus on HF, and propose some approaches to avoid cardiac adverse events in patients with IBD.
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Affiliation(s)
- Thais Gagno Grillo
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil
| | | | - Ana Elisa Valencise Quaglio
- Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University, Botucatu, Botucatu 18618689, Brazil
| | - Renata de Medeiros Dutra
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil
| | - Julio Pinheiro Baima
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil
| | - Silmeia Garcia Zanati Bazan
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil.
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2
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Lenti MV, Scribano ML, Biancone L, Ciccocioppo R, Pugliese D, Pastorelli L, Fiorino G, Savarino E, Caprioli FA, Ardizzone S, Fantini MC, Tontini GE, Orlando A, Sampietro GM, Sturniolo GC, Monteleone G, Vecchi M, Kohn A, Daperno M, D’Incà R, Corazza GR, Di Sabatino A. Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease. Front Med (Lausanne) 2023; 10:1031998. [PMID: 37113615 PMCID: PMC10126747 DOI: 10.3389/fmed.2023.1031998] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 03/14/2023] [Indexed: 04/29/2023] Open
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.
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Affiliation(s)
- Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy
| | | | - Livia Biancone
- Unit of Gastroenterology, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi and University of Verona, Verona, Italy
| | - Daniela Pugliese
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Luca Pastorelli
- Liver and Gastroenterology Unit, ASST Santi Paolo e Carlo, Milan, Italy
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Gionata Fiorino
- IBD Unit, Ospedale San Camillo-Forlanini, Rome, Italy
- Department of Gastroenterology, San Raffaele Hospital and Vita-Salute San Raffaele University,, Milan, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Flavio Andrea Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda, Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy
| | - Sandro Ardizzone
- Gastroenterology and Digestive Endoscopy Unit, ASST Fatebenefratelli Sacco, Milan, Italy
| | - Massimo Claudio Fantini
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria (AOU) di Cagliari, Cagliari, Italy
| | - Gian Eugenio Tontini
- Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
| | - Ambrogio Orlando
- Inflammatory Bowel Disease Unit, Azienda Ospedaliera Ospedali Riuniti "Villa Sofia-Cervello" Palermo, Palermo, Italy
| | | | - Giacomo Carlo Sturniolo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Giovanni Monteleone
- Unit of Gastroenterology, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda, Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy
| | - Anna Kohn
- Gastroenterology Operative Unit, Azienda Ospedaliera San Camillo-Forlanini FR, Rome, Italy
| | - Marco Daperno
- Division of Gastroenterology, Ospedale Ordine Mauriziano di Torino, Turin, Italy
| | - Renata D’Incà
- Department of Gastroenterology, San Raffaele Hospital and Vita-Salute San Raffaele University,, Milan, Italy
| | - Gino Roberto Corazza
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy
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3
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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:jcm12062432. [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] [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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4
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Pham JP, Hillman RJ, Smith A. Re: 'The impact of systemic psoriasis treatments on human papillomavirus activation and propagation'-What about anal malignancies? Australas J Dermatol 2023; 64:e204-e206. [PMID: 36807899 DOI: 10.1111/ajd.14009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 01/24/2023] [Accepted: 02/03/2023] [Indexed: 02/22/2023]
Affiliation(s)
- James P Pham
- St. Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia.,School of Clinical Medicine, UNSW Medicine and Health, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Richard J Hillman
- St. Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia.,School of Clinical Medicine, UNSW Medicine and Health, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Annika Smith
- St. Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
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5
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Incident Colorectal Cancer in Inflammatory Bowel Disease. Cancers (Basel) 2022; 14:cancers14030721. [PMID: 35158989 PMCID: PMC8833396 DOI: 10.3390/cancers14030721] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 01/25/2022] [Accepted: 01/28/2022] [Indexed: 02/01/2023] Open
Abstract
Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22-76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn's disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn's Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1-68) vs. 14.5 (8-40); p = 0.85; IBD: 12 months (1-68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients.
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6
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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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7
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Alkhayyat M, Abureesh M, Gill A, Khoudari G, Abou Saleh M, Mansoor E, Regueiro M. Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy. Inflamm Bowel Dis 2021; 27:1052-1060. [PMID: 33051651 DOI: 10.1093/ibd/izaa252] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Chronic inflammation is a key factor for the development of colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD). Despite the increased use of biologic agents in patients with IBD, their impact on colorectal carcinogenesis remains unclear. With the use of a large database, we sought to describe the effect of biologics on CRC among patients with IBD. METHODS We evaluated a multicenter database (Explorys) consisting of electronic medical records from several U.S. hospitals between 1999 and 2020. A cohort of patients with a diagnosis of IBD was identified. We performed a multivariate analysis to adjust for multiple factors including medical and surgical therapies. RESULTS There were a total of 62,007,510 patients in the database between 1999 and 2020. Amongst those, 225,090 (0.36%) individuals had Crohn's disease and 188,420 (0.30%) had ulcerative colitis. After adjusting for confounding factors using multivariate analysis, patients with IBD were more likely to develop CRC. Among the IBD cohort, patients treated with anti-TNF agents were less likely to develop CRC; patients with Crohn's disease: odds ratio, 0.69; 95% confidence interval, 0.66-0.73; P < 0.0001 vs patients with ulcerative colitis: odds ratio, 0.78; 95% confidence interval, 0.73-0.83; P < 0.0001. CONCLUSIONS Patients with IBD who were treated with anti-tumor necrosis factor agents were less likely to develop CRC. Prospective studies are needed to evaluate whether anti-tumor necrosis factor drugs provide a chemoprotective effect in patients with IBD by inflammation control and mucosal healing.
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Affiliation(s)
- Motasem Alkhayyat
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Mohammad Abureesh
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, New York, USA
| | - Arshpal Gill
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, New York, USA
| | - George Khoudari
- Department of Hospital Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Mohannad Abou Saleh
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Emad Mansoor
- Department of Gastroenterology and Liver Disease, Case Western Reserve University/University Hospitals, Cleveland, Ohio, USA
| | - Miguel Regueiro
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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8
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van de Ven SEM, Derikx LAAP, Nagtegaal ID, van Herpen CM, Takes RP, Melchers WJG, Pierik M, van den Heuvel T, Verhoeven RHA, Hoentjen F, Nissen LHC. Laryngeal Carcinoma in Patients With Inflammatory Bowel Disease: Clinical Outcomes and Risk Factors. Inflamm Bowel Dis 2020; 26:1060-1067. [PMID: 31559415 PMCID: PMC7301406 DOI: 10.1093/ibd/izz210] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients are at increased risk for developing extra-intestinal malignancies, mainly due to immunosuppressive medication. The risk of developing head and neck cancer in immunosuppressed transplant patients is increased. The relation between IBD patients and laryngeal cancer (LC) remains unclear. We aimed (1) to identify risk factors in IBD patients for LC development and (2) to compare clinical characteristics, outcome, and survival of LC in IBD patients with the general population. METHODS All IBD patients with LC (1993-2011) were retrospectively identified using the Dutch Pathology Database. We performed 2 case-control studies: (1) to identify risk factors, we compared patients with IBD and LC (cases) with the general IBD population; (2) to analyze LC survival, we compared cases with controls from the general LC population. RESULTS We included 55 cases, 1800 IBD controls, and 2018 LC controls. Cases were more frequently male compared with IBD controls (P < 0.001). For ulcerative colitis (UC), cases were older at IBD diagnosis (P < 0.001). Crohn's disease (CD) cases were more frequently tobacco users (P < 0.001) and more often had stricturing (P = 0.006) and penetrating (P = 0.008) disease. We found no survival difference. Immunosuppressive medication had no impact on survival. CONCLUSIONS Male sex was a risk factor for LC in IBD patients. Older age at IBD diagnosis was a risk factor for UC to develop LC. Tobacco use and stricturing and penetrating disease were risk factors for LC development in CD patients. Inflammatory bowel disease was not associated with impaired survival of LC. Immunosuppressive medication had no influence on survival.
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Affiliation(s)
- Steffi E M van de Ven
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Lauranne A A P Derikx
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Carla M van Herpen
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Robert P Takes
- Department of Otolaryngology and Head and Neck Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Willem J G Melchers
- Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Marieke Pierik
- Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Tim van den Heuvel
- Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Rob H A Verhoeven
- Department of Research & Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Frank Hoentjen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - L H C Nissen
- Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, the Netherlands,Address correspondence to: Loes H. C. Nissen, PhD, Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, Henri Dunantstraat 1, Postbox 90153, 5200 ME ‘s-Hertogenbosch, the Netherlands ()
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9
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Biancone L, Armuzzi A, Scribano ML, Castiglione F, D'Incà R, Orlando A, Papi C, Daperno M, Vecchi M, Riegler G, Fries W, Alvisi P, Meucci G, Mocciaro F, Rogai F, Festa S, Guidi L, Testa A, Spina L, Renna S, Viola A, Patturelli M, Di Mitri R, Frankovic I, Calabrese E, Petruzziello C, De Cristofaro E, Sena G, Ruffa A, Neri B, Rossi A. Cancer Risk in Inflammatory Bowel Disease: A 6-Year Prospective Multicenter Nested Case-Control IG-IBD Study. Inflamm Bowel Dis 2020; 26:450-459. [PMID: 31498388 DOI: 10.1093/ibd/izz155] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND In a 6-year, multicenter, prospective nested case-control study, we aimed to evaluate risk factors for incident cancer in inflammatory bowel disease (IBD), when considering clinical characteristics of IBD and immunomodulator use. The secondary end point was to provide characterization of incident cancer types. METHODS All incident cases of cancer occurring in IBD patients from December 2011-2017 were prospectively recorded in 16 Italian Group for the Study of Inflammatory Bowel Disease units. Each of the IBD patients with a new diagnosis of cancer was matched with 2 IBD patients without cancer, according to IBD phenotype (ulcerative colitis [UC] vs Crohn's disease [CD]), age (±5 years), sex. Risk factors were assessed by multivariate logistic regression analysis. RESULTS Cancer occurred in 403 IBD patients: 204 CD (CD cases), 199 UC (UC cases). The study population included 1209 patients (403 IBD cases, 806 IBD controls). Cancer (n = 403) more frequently involved the digestive system (DS; 32%), followed by skin (14.9%), urinary tract (9.7%), lung (6.9%), genital tract (6.5%), breast (5.5%), thyroid (1.9%), lymphoma (2.7%, only in CD), adenocarcinoma of the small bowel (SBA; 3.9%, 15 CD, 1 pouch in UC), other cancers (15.9%). Among cancers of the DS, colorectal cancer (CRC) more frequently occurred in UC (29% vs 17%; P < 0.005), whereas SBA more frequently occurred in CD (13% vs 6.3% P = 0.039). In CD, perforating (B3) vs non-stricturing non-perforating (B1) behavior represented the only risk factor for any cancer (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.33-4.11). In CD, risk factors for extracolonic cancer (ECC) were a B3 vs B1 and a stricturing (B2) vs B1 behavior (OR, 2.95; 95% CI, 1.62-5.43; OR, 1.79; 95% CI, 1.09-2.98). In UC, risk factors for ECC and for overall cancer were abdominal surgery for UC (OR, 4.63; 95% CI, 2.62-8.42; OR, 3.34; 95% CI, 1.88-5.92) and extensive vs distal UC (OR, 1.73; 95% CI, 1.10-2.75; OR, 1.99; 95% CI, 1.16-3.47). Another risk factor for ECC was left-sided vs distal UC (OR, 1.68; 95% CI, 1.00-2.86). Inflammatory bowel disease duration was a risk factor for skin and urinary tract cancers. CONCLUSIONS Perforating CD, extensive UC, and abdominal surgery for UC were identified as risk factors for overall incident cancer and for ECC. The clinical characteristics associated with severe IBD may increase cancer risk.
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Affiliation(s)
- Livia Biancone
- Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy
| | - Alessandro Armuzzi
- IBD Unit, Presidio Columbus Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica del Sacro Cuore, Rome, Italy
| | | | | | - Renata D'Incà
- IBD Unit, Gastroenterology, Azienda-Università of Padova, Padua, Italy
| | | | | | - Marco Daperno
- AO Ordine Mauriziano, SC Gastroenterologia, Turin, Italy
| | - Maurizio Vecchi
- University of Milan, IRCCS Ca' Granda, Ospedale Maggiore Policlinico Foundation, Milan, Italy
| | - Gabriele Riegler
- Università degli Studi della Campania Luigi Vanvitelli, Napoli, Italy
| | - Walter Fries
- IBD Unit, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | | | | | - Filippo Mocciaro
- GI and Endoscopy Unit, ARNAS Civico Di Cristina-Benfratelli, Palermo, Italy
| | | | | | - Luisa Guidi
- IBD Unit, Presidio Columbus Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica del Sacro Cuore, Rome, Italy
| | | | | | - Sara Renna
- IBD Unit, "Villa Sofia-Cervello" Hospital, Palermo, Italy
| | - Anna Viola
- IBD Unit, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Marta Patturelli
- Università degli Studi della Campania Luigi Vanvitelli, Napoli, Italy
| | - Roberto Di Mitri
- GI and Endoscopy Unit, ARNAS Civico Di Cristina-Benfratelli, Palermo, Italy
| | - Iris Frankovic
- IBD Unit, Gastroenterology, Azienda-Università of Padova, Padua, Italy
| | - Emma Calabrese
- Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy
| | - Carmelina Petruzziello
- Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy
| | - Elena De Cristofaro
- Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy
| | - Giorgia Sena
- Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy
| | - Alessandra Ruffa
- Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy
| | - Benedetto Neri
- Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy
| | - Alessandra Rossi
- Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy
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10
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Waljee AK, Higgins PDR, Jensen CB, Villumsen M, Cohen-Mekelburg SA, Wallace BI, Berinstein JA, Allin KH, Jess T. Anti-tumour necrosis factor-α therapy and recurrent or new primary cancers in patients with inflammatory bowel disease, rheumatoid arthritis, or psoriasis and previous cancer in Denmark: a nationwide, population-based cohort study. Lancet Gastroenterol Hepatol 2019; 5:276-284. [PMID: 31836320 DOI: 10.1016/s2468-1253(19)30362-0] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 10/11/2019] [Accepted: 10/14/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Safety of anti-tumour necrosis factor-α (TNFα) therapy in people with a history of cancer and with an immune-mediated disease is unknown. We aimed to assess the risk of recurrence of initial cancer or development of a new primary cancer after treatment with anti-TNFα therapy. METHODS In this Danish, population-based cohort study we recruited adults (≥18 years) with inflammatory bowel disease (IBD), rheumatoid arthritis, or psoriasis and a primary cancer diagnosed between Jan 1, 1999 and Dec 31, 2016. Patients were recruited from the prospectively recorded Danish National Patient Registry and the Danish Cancer Registry. Participants were matched 1:10 between the treatment group who received anti-TNFα therapy and the control group (no anti-TNFα therapy) and we excluded individuals with a cancer diagnosed before their first anti-TNFα treatment (or before matching date for controls), individuals diagnosed with IBD, rheumatoid arthritis, or psoriasis after anti-TNFα initiation (or respective match date for controls), and individuals who received anti-TNFα with fewer than five matched controls. Using adjusted Cox proportional hazards regression, we estimated the primary outcome of development of recurrent or new primary cancer in patients who received anti-TNFα therapy compared with patients who did not receive this therapy, matched by sex, immune-mediated disease type, cancer type, and time from initial cancer diagnosis to first anti-TNFα registration. FINDINGS Overall, 25 738 patients with immune-mediated disease and a history of cancer were identified. 434 patients who received anti-TNFα therapy after their initial cancer were matched to 4328 patients in the control group. During 18 752 person-years (median 5·6 years [IQR 2·8-7·9]) of follow up, 635 individuals developed recurrent or new primary cancer, 72 of whom had received anti-TNFα therapy and 563 of whom were in the control group. The median time between anti-TNFα treatment and recurrent or new primary cancer diagnosis was 2·8 years (IQR 1·7-5·4). The incidence of recurrent or new primary cancer development was 30·3 cases (95% CI 24·0-38·2) per 1000 person-years in the anti-TNFα treatment group and 34·4 cases (31·7-37·3) per 1000 person-years in the control group, yielding an adjusted hazard ratio of 0·82 (95% CI 0·61-1·11). INTERPRETATION Use of anti-TNFα therapy was not associated with recurrent or new primary cancer development in patients with previous cancer. Timing of anti-TNFα therapy after an initial cancer diagnosis did not influence recurrent or new primary cancer development. This observation might guide clinical decision making among providers treating immune-mediated diseases with anti-TNFα medications. FUNDING None.
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Affiliation(s)
- Akbar K Waljee
- VA Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Institute for Healthcare Policy and Innovation, University of Michigan Medical School, Ann Arbor, MI, USA; Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, MI, USA.
| | - Peter D R Higgins
- Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Camilla B Jensen
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region, Copenhagen, Denmark
| | - Marie Villumsen
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region, Copenhagen, Denmark
| | - Shirley A Cohen-Mekelburg
- VA Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Institute for Healthcare Policy and Innovation, University of Michigan Medical School, Ann Arbor, MI, USA; Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Beth I Wallace
- VA Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Institute for Healthcare Policy and Innovation, University of Michigan Medical School, Ann Arbor, MI, USA; Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Jeffrey A Berinstein
- Institute for Healthcare Policy and Innovation, University of Michigan Medical School, Ann Arbor, MI, USA; Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Kristine H Allin
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region, Copenhagen, Denmark
| | - Tine Jess
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region, Copenhagen, Denmark; Department of Clinical Medicine, University of Aalborg, Aalborg, Denmark; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
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11
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Loo SY, Vutcovici M, Bitton A, Lakatos PL, Azoulay L, Suissa S, Brassard P. Risk of Malignant Cancers in Inflammatory Bowel Disease. J Crohns Colitis 2019; 13:1302-1310. [PMID: 30874294 PMCID: PMC6764102 DOI: 10.1093/ecco-jcc/jjz058] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To explore the trends and the predictors of incident malignant cancer among patients with inflammatory bowel disease [IBD]. METHODS We identified a cohort of all patients with incident IBD in Quebec, Canada, from 1998 to 2015, using provincial administrative health-care databases [RAMQ and Med-Echo]. Annual incidence rates [IRs] of cancer were calculated using Poisson regression and were compared with those of the Quebec population using standardized incidence ratios [SIRs ]. Temporal trends in these rates were evaluated by fitting generalized linear models. Conditional logistic regression was used to estimate odds ratios [ORs] for predictors associated with cancer development. RESULTS The cohort included 35 985 patients with IBD, of which 2275 developed cancers over a mean follow-up of 8 years (IR 785.6 per 100 000 persons per year; 95% confidence interval [CI] 754.0-818.5). The rate of colorectal cancer decreased significantly from 1998 to 2015 [p < 0.05 for linear trend], but the incidence remained higher than expected, compared with the Quebec population [SIR 1.39; 95% CI 1.19-1.60]. Rates of extraintestinal cancers increased non-significantly over time [p = 0.11 for linear trend]. In the IBD cohort, chronic kidney disease [OR 1.29; 95% CI 1.17-1.43], respiratory diseases [OR 1.07; 95% CI 1.02-1.12], and diabetes mellitus [OR 1.06; 95% CI 1.01-1.11] were associated with an increase in the incidence of cancer. CONCLUSIONS The decreasing rates of colorectal cancer suggest improved management and care in IBD. Further studies are needed to explore the impact of comorbid conditions on the risk of cancer in IBD.
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Affiliation(s)
- Simone Y Loo
- Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada
| | - Maria Vutcovici
- Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada
| | - Alain Bitton
- Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada
| | - Peter L Lakatos
- Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada,1st Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Laurent Azoulay
- Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada,Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada
| | - Samy Suissa
- Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Paul Brassard
- Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada,Corresponding author: Paul Brassard, MD MSc., Centre for Clinical Epidemiology H-424, Lady Davis Research Institute, Jewish General Hospital, 3755 chemin de la Côte St-Catherine, Montreal [Quebec] H3T 1E2, Canada. Tel: [514] 340-7563; Fax: [514] 340-7564;
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12
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Ferraro S, Leonardi L, Convertino I, Blandizzi C, Tuccori M. Is There a Risk of Lymphoma Associated With Anti-tumor Necrosis Factor Drugs in Patients With Inflammatory Bowel Disease? A Systematic Review of Observational Studies. Front Pharmacol 2019; 10:247. [PMID: 30941038 PMCID: PMC6433961 DOI: 10.3389/fphar.2019.00247] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 02/26/2019] [Indexed: 01/02/2023] Open
Abstract
Background: Inflammatory bowel diseases (IBDs) are generally not considered a risk factor for the development of lymphoma. When considering IBD treatments, there is good evidence supporting thiopurines (azathioprine, 6-mercaptopurine) as a risk factor for lymphoma. Conversely, the association between the use of anti-TNF agents and the development of lymphoma remains undetermined. In this systematic review, we analyzed the evidence coming from observational studies supporting an association between the use of anti-TNF drugs and lymphoma in patients with IBDs. Methods: This systematic review was performed according with MOOSE and PRISMA statements. We searched observational studies conducted on IBD patients, using MEDLINE, EMBASE, and Google Scholar, published in English language, within the period ranging from January 1st, 1999 to June 30th, 2018. An assessment of the methodologic shortcomings of selected studies was performed as well. Results: Fourteen studies met the eligibility criteria and were included in the review. Only four studies found a significant association of anti-TNF drug with lymphoma or groups of cancers including lymphoma. However, the methodologic shortcomings of all the included studies made their results unreliable, irrespectively of whether their findings supported an association or not. Conclusions: Current evidence from observational studies does not allow excluding or confirming an association of the exposure to anti-TNF treatments with lymphoma in IBD patients.
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Affiliation(s)
- Sara Ferraro
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Luca Leonardi
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Irma Convertino
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Corrado Blandizzi
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.,Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Pisa, Italy
| | - Marco Tuccori
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.,Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Pisa, Italy
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13
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Vuitton L, Jacquin E, Parmentier AL, Crochet E, Fein F, Dupont-Gossart AC, Plastaras L, Bretagne CH, Mauny F, Koch S, Prétet JL, Mougin C, Valmary-Degano S. High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease. Clin Gastroenterol Hepatol 2018; 16:1768-1776.e5. [PMID: 29551740 DOI: 10.1016/j.cgh.2018.03.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 02/27/2018] [Accepted: 03/09/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France. METHODS We analyzed anal tissue samples collected from 469 consecutive patients (median age 54 years, 52% women), including 112 who received immunosuppressant therapies and 101 with inflammatory bowel disease (70 with Crohn's disease), who underwent colonoscopy examinations from April 1, 2012 to April 30, 2015. HPV was detected and genotyped using the INNO-LiPA assay, and we collected medical and demographic data from all subjects. Risk factors for any HPV, high-risk HPV (HR-HPV) and HPV16 infection were assessed by bivariate and multivariate analysis. The primary outcomes association of HR-HPV or HPV16 with medical and demographic features. RESULTS We detected HPV DNA in anal tissues from 34% of the subjects and HR-HPV in 18%. HPV16 was the most prevalent genotype (detected in 7%), followed by HPV51, HPV52, and HPV39. HR-HPV was detected in a significantly higher proportion of samples from women (23.1%) than men (12.8%) (P = .0035); HR-HPV and HPV16 were detected in a significantly higher proportion of patients with Crohn's disease (30.0%) than without (18.1%) (P = .005). Female sex, history of sexually transmitted disease, lifetime and past year-number of sexual partners, active smoking, and immunosuppressive therapies were independent risk factors for anal HR-HPV infection in multivariate analysis. CONCLUSION One third of patients who underwent colonoscopy at a gastroenterology department were found to have anal canal HPV infection. We detected HR-HPV infection in almost 20% of patients and in a significantly higher proportion of patients with Crohn's disease than without. Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening.
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Affiliation(s)
- Lucine Vuitton
- Department of Gastroenterology, University Hospital of Besançon, Besançon, France; EA3181, Université Bourgogne Franche-Comté, LAbEx LipSTIC ANR-11-LABX-0021, National Reference Center, Besançon, France.
| | - Elise Jacquin
- EA3181, Université Bourgogne Franche-Comté, LAbEx LipSTIC ANR-11-LABX-0021, National Reference Center, Besançon, France
| | | | - Elise Crochet
- Department of Gastroenterology, University Hospital of Besançon, Besançon, France
| | - Francine Fein
- Department of Gastroenterology, University Hospital of Besançon, Besançon, France
| | | | - Laurianne Plastaras
- Department of Gastroenterology, University Hospital of Besançon, Besançon, France; Department of Hepato-gastroenterology, Colmar General Hospital, Colmar, France
| | | | - Frédéric Mauny
- Centre de Méthodologie Clinique, University Hospital of Besançon, Besançon, France
| | - Stéphane Koch
- Department of Gastroenterology, University Hospital of Besançon, Besançon, France
| | - Jean-Luc Prétet
- EA3181, Université Bourgogne Franche-Comté, LAbEx LipSTIC ANR-11-LABX-0021, National Reference Center, Besançon, France; Department of Pathology, University Hospital of Besançon, Besançon, France
| | - Christiane Mougin
- EA3181, Université Bourgogne Franche-Comté, LAbEx LipSTIC ANR-11-LABX-0021, National Reference Center, Besançon, France; Department of Pathology, University Hospital of Besançon, Besançon, France
| | - Séverine Valmary-Degano
- EA3181, Université Bourgogne Franche-Comté, LAbEx LipSTIC ANR-11-LABX-0021, National Reference Center, Besançon, France; Department of Pathology, University Hospital of Besançon, Besançon, France
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14
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Yang C, Huang J, Huang X, Huang S, Cheng J, Liao W, Chen X, Wang X, Dai S. Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-tumour Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis. J Crohns Colitis 2018; 12:1042-1052. [PMID: 29762681 DOI: 10.1093/ecco-jcc/jjy065] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 05/04/2018] [Accepted: 05/11/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS The association between anti-tumour necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumour necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. METHODS MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumour necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. RESULTS Twelve studies comprising 285,811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumour necrosis factor alpha agents exposed and anti-tumour necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR] = 1.43, 95% CI, 0.91-2.25; P = 0.116; random effects: risk ratio [RR] = 0.83, 95% CI, 0.47-1.48; P = 0.534). However, monotherapy of anti-tumour necrosis factor alpha agents [random effects: IRR = 1.65, 95% CI, 1.16-2.35; P = 0.006; random effects: RR = 1.00, 95% CI, 0.39-2.59; P = 0.996] or combination therapy [random effects: IRR = 3.36, 95% CI, 2.23-5.05; P < 0.001; random effects: RR = 1.90, 95% CI, 0.66-5.44; P = 0.233] can significantly increase the risk of lymphoma. CONCLUSIONS Exposition of anti-tumour necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumour necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.
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Affiliation(s)
- Chen Yang
- First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Junlin Huang
- First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiaowen Huang
- First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Shaozhuo Huang
- First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiaxin Cheng
- Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Weixin Liao
- First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Xuewen Chen
- First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Xueyi Wang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Shixue Dai
- Department of Gastroenterology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, South China University of Technology, Guangzhou, Guangdong, China.,Guangdong Geriatrics Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, South China University of Technology, Guangzhou, Guangdong, China
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15
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Anti-TNF Therapy in Crohn's Disease. Int J Mol Sci 2018; 19:ijms19082244. [PMID: 30065229 PMCID: PMC6121417 DOI: 10.3390/ijms19082244] [Citation(s) in RCA: 180] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 07/04/2018] [Accepted: 07/07/2018] [Indexed: 02/06/2023] Open
Abstract
Crohn’s disease (CD) accounts for a variety of clinical manifestations or phenotypes that stem from chronic inflammation in the gastrointestinal tract. Its worldwide incidence is increasing including younger or childhood-onset of disease. The natural history of Crohn’s disease is characterized by a remitting and relapsing course that progresses to complications and surgery in most patients. The goals of treatment are to achieve clinical and endoscopic remission, to avoid disease progression and minimise surgical resections. Medical treatment usually features antibiotics, corticosteroids, immunomodulators (thiopurines, methotrexate). Anti-TNF (tumour necrosis factor) therapy was approved for use in Crohn’s disease in 1998, and has changed the paradigm of treatment, leading to improved rates of response and remission in patients. There are significant considerations that need to be borne in mind, when treating patients including immunogenicity, safety profile and duration of treatment.
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16
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Biancone L, Annese V, Ardizzone S, Armuzzi A, Calabrese E, Caprioli F, Castiglione F, Comberlato M, Cottone M, Danese S, Daperno M, D'Incà R, Frieri G, Fries W, Gionchetti P, Kohn A, Latella G, Milla M, Orlando A, Papi C, Petruzziello C, Riegler G, Rizzello F, Saibeni S, Scribano ML, Vecchi M, Vernia P, Meucci G, Bossa F, Cappello M, Cassinotti A, Chiriatti A, Fiorino G, Formica V, Guidi L, Losco A, Mocciaro F, Onali S, Pastorelli L, Pica R, Principi M, Renna S, Ricci C, Rispo A, Rogai F, Sarmati L, Scaldaferri F, Spina L, Tambasco R, Testa A, Viscido A. Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Dig Liver Dis 2017; 49:338-358. [PMID: 28161290 DOI: 10.1016/j.dld.2017.01.141] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 12/19/2016] [Accepted: 01/07/2017] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.
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Affiliation(s)
- Livia Biancone
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy.
| | - Vito Annese
- AOU Careggi, Gastroenterology, Florence, Italy
| | - Sandro Ardizzone
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco - University of Milan, Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit, Presidio Columbus, Fondazione Policlinico Gemelli Universita' Cattolica, Rome, Italy
| | - Emma Calabrese
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation, University of Milan and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda,Ospedale Policlinico di Milano, Milan, Italy
| | | | - Michele Comberlato
- Department of Gastroenterology and Digestive Endoscopy, Central Hospital, Bolzano, Italy
| | - Mario Cottone
- Division of Internal Medicine 2, IBD Unit, Hospital "Riuniti Villa Sofia-Cervello", Palermo, Italy
| | - Silvio Danese
- Humanitas Research Hospital and Humanitas University, Rozzano (Milan), Italy
| | - Marco Daperno
- Hospital "Ordine Mauriziano di Torino", Turin, Italy
| | - Renata D'Incà
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Italy
| | - Giuseppe Frieri
- University of L'Aquila, Gastroenterology Unit, L'Aquila, Italy
| | - Walter Fries
- Department of Clinical and Experimental Medicine, Clinical Unit for Chroric Bowel Disorders, University of Messina, Messina, Italy
| | - Paolo Gionchetti
- IBD Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Anna Kohn
- San Camillo-Forlanini Hospital, IBD Unit, Rome, Italy
| | | | | | - Ambrogio Orlando
- Division of Internal Medicine 2, IBD Unit, Hospital "Riuniti Villa Sofia-Cervello", Palermo, Italy
| | - Claudio Papi
- IBD Unit, San Filippo Neri Hospital, Rome, Italy
| | - Carmelina Petruzziello
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy
| | - Gabriele Riegler
- U.O. of Gastroenterology C.S. - University della Campania "Luigi Vanvitelli", Naples, Italy
| | - Fernando Rizzello
- IBD Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Simone Saibeni
- Gastroenterology Unit, Rho Hospital, ASST Rhodense, Rho, Italy
| | | | - Maurizio Vecchi
- Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato and University of Milan, San Donato Milanese, Milan, Italy
| | - Piero Vernia
- Gastroenterology Unit, Sapienza, University of Rome, Rome, Italy
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Incidence of renal cell carcinoma in inflammatory bowel disease patients with and without anti-TNF treatment. Eur J Gastroenterol Hepatol 2017; 29:84-90. [PMID: 27603297 DOI: 10.1097/meg.0000000000000735] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE We aimed to study the risk of renal cell carcinoma (RCC) with anti-tumor necrosis factor (anti-TNF) therapy in inflammatory bowel disease (IBD) and rheumatic diseases (RD) and calculate standardized incidence ratios (SIRs) in IBD. MATERIALS AND METHODS This was a retrospective case-control and cohort study spanning 25 years, including IBD and RD patients with a diagnosis of RCC (1990-2014) identified through the electronic database of a tertiary referral center. RESULTS RCC was confirmed in seven anti-TNF-exposed (TNF+) and 21 anti-TNF-naive (TNF-) IBD and one TNF+ and 26 TNF- RD patients. In IBD-RCC, younger age at RCC diagnosis [median (interquartile range) 46 (42-58) vs. 63 (52-75) years; P=0.02], immunosuppressive therapy (100 vs. 24%; P<0.0004), partial nephrectomy (86 vs. 33%; P=0.02), and surgery less than 1 month after diagnosis of RCC (71 vs. 14%; P=0.004) were associated with anti-TNF. Compared with IBD, RD patients were older at RCC diagnosis [70 (60-77) vs. 59 (47-69) years; P=0.02] with less nephron-sparing surgery (26 vs. 54%; P=0.04) and more symptomatic (44 vs. 14%; P=0.02) and advanced tumors (30 vs. 7%; P=0.04). SIRs in IBD-RCC TNF- and TNF+ were 5.4 (95% confidence interval 2.9-9.2) and 7.1 (2.3-16.5) in male patients and 8.5 (3.7-16.8) and 4.8 (0.6-17.3) in female patients, respectively. The risk for RCC associated with anti-TNF in IBD was 0.8 (0.3-2.5) in men and 1.4 (0.2-5.5) in women. CONCLUSION The favorable patient and tumor profiles in IBD with anti-TNF may suggest incidentally discovered RCC on abdominal imaging. SIRs for IBD-RCC were not increased after anti-TNF exposure.
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Dulai PS, Sandborn WJ, Gupta S. Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management. Cancer Prev Res (Phila) 2016; 9:887-894. [PMID: 27679553 DOI: 10.1158/1940-6207.capr-16-0124] [Citation(s) in RCA: 126] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 08/25/2016] [Accepted: 08/30/2016] [Indexed: 02/07/2023]
Abstract
Crohn disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) characterized by recurrent episodes of mucosal inflammation. This chronic mucosal inflammation has several potential consequences, one of which is the occurrence of colitis-associated colorectal cancer. Over the past decade, our understanding of the epidemiology, pathophysiology, and overall approach to diagnosing and managing colitis-associated colorectal cancer has grown considerably. In the current review article, we outline these advancements and highlight areas in need of further research. Cancer Prev Res; 9(12); 887-94. ©2016 AACR.
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Affiliation(s)
- Parambir S Dulai
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Samir Gupta
- Division of Gastroenterology, University of California San Diego, La Jolla, California. .,Veterans Affairs San Diego Healthcare System, San Diego, California.,Moores Cancer Center, University of California San Diego, La Jolla, California
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19
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Biancone L, Armuzzi A, Scribano ML, D'Inca R, Castiglione F, Papi C, Angelucci E, Daperno M, Mocciaro F, Riegler G, Fries W, Meucci G, Alvisi P, Spina L, Ardizzone S, Petruzziello C, Ruffa A, Kohn A, Vecchi M, Guidi L, Di Mitri R, Renna S, Emma C, Rogai F, Rossi A, Orlando A, Pallone F. Inflammatory Bowel Disease Phenotype as Risk Factor for Cancer in a Prospective Multicentre Nested Case-Control IG-IBD Study. J Crohns Colitis 2016; 10:913-24. [PMID: 26933032 DOI: 10.1093/ecco-jcc/jjw048] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Accepted: 02/09/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Cancer risk in inflammatory bowel disease [IBD] is still debated. In a prospective, multicentre, nested case-control study, we aimed to characterise incident cases of cancer in IBD. The role of immunomodulators vs clinical characteristics of IBD as risk factors for cancer was also investigated. MATERIALS AND METHODS From January 2012 to December 2014, each IBD patient with incident cancer was matched with two IBD patients without cancer for: IBD type, gender, and age. Risk factors were assessed by multivariate regression analysis. RESULTS IBD patients considered numbered 44619: 21953 Crohn's disease [CD], 22666 ulcerative colitis [UC]. Cancer occurred in 174 patients: 99 CD [CD-K], 75 UC [UC-K]. Controls included 198 CD [CD-C], 150 UC [UC-C]. Cancer incidence in IBD was 3.9/1000, higher in CD (4.5/1000 [99/21,953]) than in UC (3.3/1000 [75/22,666]; p = 0.042). Cancers involved: digestive system [36.8%], skin [13.2%], urinary tract [12.1%], lung [8.6%], breast [8%], genital tract [6.9%], thyroid [4.6%], lymphoma [3.5%], others [6.3%]. In CD, penetrating behaviour and combined thiopurines and tumour necrosis factor alpha [TNFα] antagonists were risk factors for cancer overall: odds ratio [OR] (95% confidence interval [CI] 2.33 [1.01-5.47]); 1.97 [1.1-3.5]; and for extracolonic cancers 3.9 [1.56-10.1]; 2.15 [1.17-4.1], respectively. In UC, risk factors were pancolitis and disease-related surgery for cancer overall (OR: 2.52 [1.26-5.1]; 5.09 [1.73-17.1]); disease-related surgery for colorectal cancer [CRC] (OR 3.6 [1.0-12]); and extensive and left-sided vs distal UC for extracolonic cancers (OR: 2.55 [1.15-5.9]; 2.6 [1.04-6.6]), respectively. CONCLUSIONS In a multicentre study, penetrating CD and extensive UC were risk factors for cancer overall. Cancer incidence was higher in CD than in UC.
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Affiliation(s)
- Livia Biancone
- Department of Systems Medicine, Gastroenterology Unit, University 'Tor Vergata', Rome, Italy
| | - Alessandro Armuzzi
- Department of Internal Medicine, Division of Gastroenterology, Columbus, Catholic University and IBD Unit, Rome, Italy
| | | | - Renata D'Inca
- Department of Gastroenterology, U.O. Gastroenterology, University of Padua, Padua, Italy
| | | | | | - Erika Angelucci
- Department of Systems Medicine, Gastroenterology Unit, University 'Tor Vergata', Rome, Italy
| | - Marco Daperno
- GI Unit, A.O. Ordine Mauriziano di Torino, Turin, Italy
| | | | | | - Walter Fries
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | | | | | - Luisa Spina
- Department of Biomedical Sciences for Health, University of Milan, and GI Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
| | | | - Carmelina Petruzziello
- Department of Systems Medicine, Gastroenterology Unit, University 'Tor Vergata', Rome, Italy
| | - Alessandra Ruffa
- Department of Systems Medicine, Gastroenterology Unit, University 'Tor Vergata', Rome, Italy
| | - Anna Kohn
- GI Unit, A.O. San Camillo-Forlanini, IBD Unit, Rome, Italy
| | - Maurizio Vecchi
- Department of Biomedical Sciences for Health, University of Milan, and GI Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
| | - Luisa Guidi
- Department of Internal Medicine, Division of Gastroenterology, Columbus, Catholic University and IBD Unit, Rome, Italy
| | | | - Sara Renna
- Division of Internal Medicine 'Villa Sofia-Cervello' Hospital, University of Palermo, Palermo, Italy
| | - Calabrese Emma
- Department of Systems Medicine, Gastroenterology Unit, University 'Tor Vergata', Rome, Italy
| | - Francesca Rogai
- Department of Medical and Surgical Specialties, Gastroenterology SOD2, A.O. Universitaria Careggi, Florence, Italy
| | - Alessandra Rossi
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Ambrogio Orlando
- Division of Internal Medicine 'Villa Sofia-Cervello' Hospital, University of Palermo, Palermo, Italy
| | - Francesco Pallone
- Department of Systems Medicine, Gastroenterology Unit, University 'Tor Vergata', Rome, Italy
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20
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Mager LF, Wasmer MH, Rau TT, Krebs P. Cytokine-Induced Modulation of Colorectal Cancer. Front Oncol 2016; 6:96. [PMID: 27148488 DOI: 10.3389/fonc.2016.00096] [Citation(s) in RCA: 162] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 04/02/2016] [Indexed: 12/12/2022] Open
Abstract
The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.
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Affiliation(s)
- Lukas F Mager
- Institute of Pathology, University of Bern , Bern , Switzerland
| | - Marie-Hélène Wasmer
- Institute of Pathology, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
| | - Tilman T Rau
- Institute of Pathology, University of Bern , Bern , Switzerland
| | - Philippe Krebs
- Institute of Pathology, University of Bern , Bern , Switzerland
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21
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Kuehn F, Mullins CS, Krohn M, Harnack C, Ramer R, Krämer OH, Klar E, Huehns M, Linnebacher M. Establishment and characterization of HROC69 - a Crohn´s related colonic carcinoma cell line and its matched patient-derived xenograft. Sci Rep 2016; 6:24671. [PMID: 27087592 PMCID: PMC4834534 DOI: 10.1038/srep24671] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 03/23/2016] [Indexed: 02/07/2023] Open
Abstract
Colitis-associated colorectal cancer (CAC) seems to be a rather unique entity and differs in its genetic alterations, tumour formation capacities, and clinical features from sporadic colorectal carcinoma. Most descriptions about tumour biology of CAC refer to ulcerative colitis; data about Crohn´s colitis related carcinomas are scarce. The majority of patients with Crohn´s disease are under immunosuppression which generates a different environment for tumour growth. We first describe the clinical case of a fast growing CAC in a long-term immunosuppressed patient with Crohn´s disease and successful establishment and characterization of carcinoma cell lines along with their corresponding patient-derived xenograft. Subsequently, these tumor models were molecularly and functionally analysed. Beside numerous chromosomal alterations, mutations in TP53, APC, PTEN and SMAD3 were identified. The cell lines express numerous cancer testis antigens, surface molecules involved in immune evasion but low levels of HLA class I molecules. They show strong invasive but in comparison weak migratory activity. The present work is the first description of patient-derived in vitro and in vivo models for CAC from a Crohn´s disease patient. They might be valuable tools for analysis of genetic and epigenetic alterations, biomarker identification, functional testing, including response prediction, and the development of specific therapeutical strategies.
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Affiliation(s)
- Florian Kuehn
- University Medicine Rostock, Department of General-, Thoracic-, Vascular- and Transplantation Surgery, Rostock, Germany
| | - Christina S Mullins
- University Medicine Rostock, Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
| | - Mathias Krohn
- University Medicine Rostock, Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
| | - Christine Harnack
- University Medicine Rostock, Department of General-, Thoracic-, Vascular- and Transplantation Surgery, Rostock, Germany
| | - Robert Ramer
- University Medicine Rostock, Institute of Toxicology and Pharmacology, Rostock, Germany
| | - Oliver H Krämer
- University Medical Center Mainz, Department of Toxicology, Mainz, Germany
| | - Ernst Klar
- University Medicine Rostock, Department of General-, Thoracic-, Vascular- and Transplantation Surgery, Rostock, Germany
| | - Maja Huehns
- University Medicine Rostock, Institute of Pathology, Rostock, Germany
| | - Michael Linnebacher
- University Medicine Rostock, Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
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22
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Annese V, Beaugerie L, Egan L, Biancone L, Bolling C, Brandts C, Dierickx D, Dummer R, Fiorino G, Gornet JM, Higgins P, Katsanos KH, Nissen L, Pellino G, Rogler G, Scaldaferri F, Szymanska E, Eliakim R. European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies. J Crohns Colitis 2015; 9:945-65. [PMID: 26294789 DOI: 10.1093/ecco-jcc/jjv141] [Citation(s) in RCA: 315] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 08/10/2015] [Indexed: 02/07/2023]
Affiliation(s)
- Vito Annese
- University Hospital Careggi, Department of Gastroenterology, Florence, Italy
| | - Laurent Beaugerie
- Department of Gastroenterology, AP-HP Hôpital Saint-Antoine, and UPMC Univ Paris 06, Paris, France
| | - Laurence Egan
- Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland
| | - Livia Biancone
- University Tor Vergata of Rome, GI Unit, Department of Systems Medicine, Rome, Italy
| | - Claus Bolling
- Agaplesion Markus Krankenhaus, Medizinische Klinik I, Frankfurt am Main, Germany
| | - Christian Brandts
- Department of Medicine, Hematology/Oncology, Goethe University, Frankfurt am Main, Germany
| | - Daan Dierickx
- Department of Haematology, University Hospital Leuven, Leuven, Belgium
| | - Reinhard Dummer
- Department of Dermatology, University Zürich, Zürich, Switzerland
| | - Gionata Fiorino
- Gastroenterology Department, Humanitas Research Hospital, Rozzano, Italy
| | - Jean Marc Gornet
- Service d'hépatogastroentérologie, Hopital Saint-Louis, Paris, France
| | - Peter Higgins
- University of Michigan, Department of Internal Medicine, Ann Arbor, USA
| | | | - Loes Nissen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Gianluca Pellino
- Second University of Naples, Unit of Colorectal Surgery, Department of Medical, Surgical, Neurological, Metabolic and Ageing Sciences, Naples, Italy
| | - Gerhard Rogler
- Klinik für Gastroenterologie und Hepatologie, UniversitätsSpital Zürich, Zürich, Switzerland
| | - Franco Scaldaferri
- Università Cattolica del Sacro Cuore, Department of Internal Medicine, Gastroenterology Division, Roma, Italy
| | - Edyta Szymanska
- Department of Pediatrics, Nutrition and Metabolic Disorders, Children's Memorial Health Institute, Warsaw, Poland
| | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Sheba Medical Center & Sackler School of Medicine, Israel
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23
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Hornbeak DM, Thorne JE. Immunosuppressive therapy for eye diseases: Effectiveness, safety, side effects and their prevention. Taiwan J Ophthalmol 2015; 5:156-163. [PMID: 29018691 PMCID: PMC5602133 DOI: 10.1016/j.tjo.2015.03.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Revised: 03/25/2015] [Accepted: 03/30/2015] [Indexed: 12/17/2022] Open
Abstract
Ocular inflammation is a significant cause of ocular morbidity and visual impairment. Topical, periocular, intraocular, and systemic corticosteroids are highly effective for treating appropriate forms of ocular inflammation. However, their use may be constrained by local and/or systemic side effects, especially if long-term therapy is required. As a result, immunosuppressive agents increasingly have been used to manage ocular inflammation alongside or in place of corticosteroids. The four categories of agents used today are antimetabolites [primarily methotrexate, mycophenolate mofetil (MMF), and azathioprine]; T-cell inhibitors (usually cyclosporine, less often tacrolimus or sirolimus); alkylating agents (cyclophos-phamide and chlorambucil); and biologic agents [tumor necrosis factor (TNF) inhibitors, lymphocyte inhibitors, and interleukin inhibitors]. The primary goals of immunosuppressive therapy are (1) to control inflammation when corticosteroids fail to do so; (2) to prevent corticosteroid-induced toxicity when the necessary corticosteroid dosage exceeds the desired or safe level (corticosteroid sparing); and (3) to treat specific high-risk uveitis syndromes known to respond poorly to corticosteroids alone. Growing evidence shows the effectiveness of immunosuppressive drugs in achieving these goals, as well as improved visual function, prevention of ocular complications, and in some cases even disease remission. However, these agents also have side effects, which must be considered in each patient's management. In this report, we summarize the effectiveness and safety of immunosuppressive drug therapy utilized in the treatment of ocular inflammatory diseases.
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Affiliation(s)
- Dana M Hornbeak
- Division of Ocular Immunology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jennifer E Thorne
- Division of Ocular Immunology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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24
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Biancone L, Onali S, Petruzziello C, Calabrese E, Pallone F. Cancer and immunomodulators in inflammatory bowel diseases. Inflamm Bowel Dis 2015; 21:674-98. [PMID: 25545375 DOI: 10.1097/mib.0000000000000243] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The widespread use of thiopurines and anti-tumor necrosis factors (TNFs) in inflammatory bowel disease (IBD) is a rising concern regarding their potential cancer risk. MEDLINE, EMBASE, and the Cochrane Library database were searched for articles regarding immunomodulators anti-TNF agents in IBD, hematologic malignancies, and solid tumors. Current evidences support that thiopurines and anti-TNFs used alone or in combination do not increase the overall cancer risk in IBD. Thiopurines use, with or without anti-TNFs, is associated with an increased risk of lymphoma, particularly non-Hodgkin lymphoma, in Crohn's disease. Combined treatment significantly increases the risk of a rare hepatosplenic T-cell lymphoma, particularly in young male patients with Crohn's disease. An increased risk of nonmelanotic skin cancer is also observed when using thiopurines in IBD, whereas a slightly increased risk of melanoma is observed when using anti-TNFs. The role played by immunomodulators in the development of other cancer types (i.e., urinary) as also by the severity of IBD is under investigation. Although the incidence of specific malignancies (lymphoma, skin cancers) seems to be increased by immunomodulators, their absolute number is low. As thiopurines and anti-TNFs are highly effective in IBD, current evidences support that in appropriate hands, their benefits overwhelm the cancer risk. However, a careful selection of both patients and timing of treatment is mandatory, particularly in young male patients with Crohn's disease. Immunomodulators should therefore be handled by experienced and dedicated gastroenterologists who aware of the potential, although low, cancer risk associated with their use in patients with IBD.
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Affiliation(s)
- Livia Biancone
- GI Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
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25
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Pagnini C, Arseneau KO, Cominelli F. Safety considerations when using anti-TNFα therapy to treat Crohn's disease. Expert Opin Drug Saf 2014; 14:31-44. [PMID: 25400161 DOI: 10.1517/14740338.2015.976610] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Over the past decade, the introduction of a new class of anti-TNFα drugs has dramatically changed the approach taken to the management of Crohn's disease (CD). An increasing number of patients are receiving treatment with these advanced biological therapies, and the risk of adverse events that may be associated with their use must be carefully evaluated. AREAS COVERED Safety data about the three anti-TNFα drugs currently approved for use in CD patients (infliximab, adalimumab, and certolizumab pegol) is critically evaluated, including data coming from randomized clinical trials and post-marketing reports. Possible side effects of anti-TNFα agents are presented as drug-, class- and disease-specific adverse events. Management strategies to minimize the occurrence of side effects are summarized. EXPERT OPINION The safety profile of the three anti-TNFα drugs approved for clinical use in CD patients appears to be comparable among drugs. Data from clinical trials and a growing body of information from post-marketing surveillance indicate that anti-TNFα agents are generally safe, and that most of the observed side effects are mild and easily manageable. Nonetheless, serious short- and long-term adverse events may occur. Accurate selection of patients, careful pre-treatment evaluation, and regular follow-up during therapy could potentially reduce the rate of adverse events related to the use of anti-TNFα drugs.
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Affiliation(s)
- Cristiano Pagnini
- "Sapienza" University of Rome, S. Andrea Hospital, Faculty of Medicine and Psychology , Rome , Italy
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26
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Mohammad F, Vivekanandarajah A, Haddad H, Shutty CM, Hurford MT, Dai Q. Acute promyelocytic leukaemia (APL) in a patient with Crohn's disease and exposure to infliximab: a rare clinical presentation and review of the literature. BMJ Case Rep 2014; 2014:bcr-2013-203318. [PMID: 24842356 DOI: 10.1136/bcr-2013-203318] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
With the introduction of potent immunosuppressive and chemotherapeutic medications for various diseases, there is an increased incidence of therapy-related myeloid neoplasms. They are the result of mutational rearrangement and historically, have a grave prognosis compared with de novo myeloid neoplasms. We did a short review on various types of myeloid leukaemias reported after therapy with antitumour necrosis factor and also report, to the best of our knowledge, one among the very few cases of therapy-related acute promyelocytic leukaemia in a patient on infliximab therapy for refractory Crohn's disease. The patient responded well to the traditional treatment and is in complete remission for more than 5 years.
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Affiliation(s)
- Farhan Mohammad
- Department of Medicine/Hematology-Oncology, Staten Island University Hospital, Staten Island, New York, USA
| | - Abhirami Vivekanandarajah
- Department of Medicine/Hematology-Oncology, Staten Island University Hospital, Staten Island, New York, USA
| | - Housam Haddad
- Department of Medicine/Hematology-Oncology, Staten Island University Hospital, Staten Island, New York, USA
| | - Christopher M Shutty
- Department of Pathology, Staten Island University Hospital, Staten Island, New York, USA
| | - Matthew T Hurford
- Department of Pathology, Staten Island University Hospital, Staten Island, New York, USA
| | - Qun Dai
- Department of Medicine/Hematology-Oncology, Staten Island University Hospital, Staten Island, New York, USA
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27
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Colorectal cancer and Crohn's colitis: clinical implications from 313 surgical patients. World J Surg 2013; 37:902-10. [PMID: 23381673 DOI: 10.1007/s00268-013-1922-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The relation between Crohn's colitis (CC) and colorectal cancer is still controversial. Several case reports and retrospective studies have shown that patients with Crohn's disease (CD) have a 6- to 20-fold higher risk to develop CRC than does the normal population. The extent of disease (extensive colitis), presence of anal fistula, age > 40 years, strictures, and length of disease >10 years may be important determinants for increasing risk. Despite this evidence, other population-based studies have shown no increased risk of colon or rectal cancer. The aim of this study was to investigate retrospectively factors that may predict the development of cancer. METHODS We searched the histopathologic database of the Digestive Surgery Unit at Careggi University Hospital for CC patients (January 1987 to September 2011) and identified 313 patients with CC who underwent surgery. RESULTS There are 11 (3.5 %) of adenocarcinomas. Multivariate analysis showed disease duration (p = 0.001), age at CD diagnosis (p = 0.002), distal localization (p = 0.045), and penetrating disease (p = 0.041) to be risk factors. Multivariate analysis showed that 40 patients who had undergone previous immunosuppressive therapy had a significant risk of developing CRC (p = 0.026). CONCLUSIONS Crohn's colitis patients who require surgery are at higher risk for developing CRC, particularly those whose disease duration is >10 years, have distal localization, age at diagnosis was <40 years, and have penetrating disease. Previous immunosuppressive therapy should be better investigated. We recommend surgery for any patient presenting with colonic strictures.
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Preoperative infliximab therapy does not increase morbidity and mortality after laparoscopic resection for inflammatory bowel disease. Dis Colon Rectum 2013; 56:449-57. [PMID: 23478612 DOI: 10.1097/dcr.0b013e3182759029] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND The impact of infliximab on the postoperative course of patients with IBD is under debate. OBJECTIVE The aim of this study was to evaluate the influence of infliximab on perioperative outcomes in patients undergoing elective laparoscopic resection for IBD. DESIGN This study is a retrospective analysis of a prospectively collected, institutional review board-approved database. SETTING, PATIENTS, INTERVENTIONS: Patients undergoing laparoscopic resection on preoperative infliximab (infliximab group) were compared with patients who did not receive infliximab (noninfliximab group). MAIN OUTCOME MEASURES The short-term and long-term morbidity and mortality rates were assessed. RESULTS Elective laparoscopic resection for IBD was performed on 518 patients from January 2004 through June 2011; 142 patients were treated with infliximab preoperatively. Both groups had similar demographics, type and severity of IBD, comorbidities, and type of surgery. A significantly higher number of patients in the infliximab group had been on aggressive medical therapy to control symptoms of IBD during the month preceding surgery, including steroids (73.9 vs 58.8%, p = 0.002) and immunosuppressors (32.4 vs 20.5%, p = 0.006). Operative time and blood loss were similar (p = 0.50 and p = 0.34). Intraoperative complication rate was 2.1% in both groups. No significant differences were observed in terms of the conversion rate to laparotomy (6.3% vs 9.3%, p = 0.36), overall 30-day postoperative morbidity (p = 0.93), or mortality (p = 0.61). The rates of anastomotic leak (2.1% vs 1.3%, p = 0.81), infections (12% vs 11.2%, p = 0.92), and thrombotic complications (3.5% vs 5.6%, p = 0.46) were similar. Subgroup analyses confirmed similar rates of overall, infectious, and thrombotic complications regardless of whether patients had ulcerative colitis or Crohn's disease. LIMITATIONS This study is subject to the limitations of a retrospective design. CONCLUSIONS Infliximab is not associated with increased rates of postoperative complications after laparoscopic resection.
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29
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Risk of extraintestinal solid cancer with anti-TNF therapy in adults with inflammatory bowel disease: review of the literature. Inflamm Bowel Dis 2013; 19:644-9. [PMID: 23314243 DOI: 10.1097/mib.0b013e318280ebbd] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
With the increased use of anti-TNF therapy for both ulcerative colitis and Crohn's disease, there is serious concern about long term adverse events, especially malignancy. Recent data suggests that anti-TNF agents increase the risk of non-Hodgkin's lymphoma; however, there is limited evidence on the risk of solid tumors. Many patients have been exposed to other immunosuppressive therapies in the past making it difficult to discern the true risk of malignancy with TNF-alpha inhibitors alone. The purpose of this review is to discuss the risk of extra-intestinal solid cancer, excluding skin cancer, in adult inflammatory bowel disease patients exposed to anti-TNF agents.
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30
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Bilateral Vocal Cord Carcinoma in a Sarcoidosis Patient during Infliximab Therapy. Case Rep Pulmonol 2013; 2013:308092. [PMID: 23762724 PMCID: PMC3671292 DOI: 10.1155/2013/308092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Accepted: 04/17/2013] [Indexed: 11/17/2022] Open
Abstract
Introduction. Although the role of TNF-α in tumor development is not fully understood, an increased risk of malignancy with TNF-α-inhibitors, such as infliximab, has been suggested. Case Presentation. We present a 54-year-old nonsmoking female sarcoidosis patient. After seven months of infliximab therapy a T1aN0M0 larynx carcinoma of the right vocal cord was found and excised. Within a year, whilst still on treatment, a second larynx carcinoma of the opposite vocal cord appeared. Discussion. A bilateral vocal cord tumor is rare, especially in a never smoker. Evidence on the role of infliximab in carcinogenesis is inconclusive. To date, there are no follow-up studies evaluating malignancy risk of infliximab therapy in sarcoidosis patients. No studies in other diseases focus on laryngeal carcinomas during infliximab use. We argue that infliximab treatment might have attributed to the rapid progression of vocal cord carcinomas in this patient with an a priori low risk tumor profile. This case illustrates that caution remains warranted in patients with previous malignancies when considering initiation of TNF-α-inhibitors.
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31
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Ueno F, Matsui T, Matsumoto T, Matsuoka K, Watanabe M, Hibi T. Evidence-based clinical practice guidelines for Crohn's disease, integrated with formal consensus of experts in Japan. J Gastroenterol 2013; 48:31-72. [PMID: 23090001 PMCID: PMC3541931 DOI: 10.1007/s00535-012-0673-1] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2012] [Accepted: 08/16/2012] [Indexed: 02/04/2023]
Abstract
Crohn's disease is a disorder of unknown etiology and complicated pathogenesis. A substantial amount of evidence has accumulated recently and has been applied to clinical practice. The present guidelines were developed based on recent evidence and the formal consensus of experts relevant to this disease. Here we provide an overview of these guidelines, as follows. Target disease: Crohn's disease Users: Clinical practitioners in internal medicine, surgery, gastroenterology, and general practice Purpose: To provide appropriate clinical indicators to practitioners Scope of clinical indicators: Concept of Crohn's disease, epidemiology, classifications, diagnosis, treatment, follow up, and special situations Intervention: Diagnosis (interview, physical examination, clinical laboratory tests, imaging, and pathology) and treatment (lifestyle guidance, drug therapy, nutritional therapy, surgery, etc.) Outcome assessment: Attenuation of symptoms, induction and maintenance of remission, imaging findings, quality of life (QOL), prevention of complications and harm of therapy Methods for developing these guidelines: Described in the text Basis of recommendations: Integration of evidence level and consensus of experts Cost-benefit analysis: Not implemented Evaluation of effectiveness: Yet to be confirmed Status of guidelines: Updated version of the first Guidelines published in 2010 Publication sources: Printed publication available and electronic information in preparation Patient information: Not available Date of publication: October 2011 These guidelines were intended primarily to be used by practitioners in Japan, and the goal of these guidelines is to improve the outcomes of patients with Crohn's disease.
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Affiliation(s)
| | - Toshiyuki Matsui
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Takayuki Matsumoto
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshifumi Hibi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
| | - On Behalf of the Guidelines Project Group of the Research Group of Intractable Inflammatory Bowel Disease subsidized by the Ministry of Health, Labour and Welfare of Japan and the Guidelines Committee of the Japanese Society of Gastroenterology
- Ofuna Chuo Hospital, Kanagawa, Japan
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
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Corte C, Saxena P, Tattersall S, Selinger C, Leong RW. When to use biological agents in inflammatory bowel disease. J Gastroenterol Hepatol 2012; 27:1141-9. [PMID: 22188169 DOI: 10.1111/j.1440-1746.2011.07056.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The use of biological agents in inflammatory bowel diseases across the Asia-Pacific region is increasing. As new molecules and targets are identified, knowledge regarding the indications, utility, optimization and adverse effects of biological agents grows. Careful patient selection, attention to communication and patient education will maximize the benefit of these drugs. Tertiary referral centers with specific interest in inflammatory bowel diseases and experience play an important role in their use. There is enormous opportunity for patients to benefit from biological agents in the therapy of Crohn's disease and ulcerative colitis. Use of these agents has been studied across a variety of indications and populations, and at different stages in the disease course. Failure to respond or loss of response can result from different causes, and can be medically managed in many cases. More research on the pleiotropic effects, safety of biological agents and biomarkers in the prediction of response will provide a sounder basis for individually directing therapy. Adverse events such as opportunistic infection and malignancy can occur, and screening prior to therapy and discussion on risk-benefit of the various management options are important. Cost of these medications especially with maintenance therapy remains an important issue in many Asia-Pacific countries. New and more specific agents will better target therapy and minimize adverse events.
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Affiliation(s)
- Crispin Corte
- Gastroenterology and Liver Services, Concord Hospital, Sydney Local Health District, Sydney, New South Wales, Australia
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Lichtenstein GR, Rutgeerts P, Sandborn WJ, Sands BE, Diamond RH, Blank M, Montello J, Tang L, Cornillie F, Colombel JF. A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease. Am J Gastroenterol 2012; 107:1051-63. [PMID: 22613901 PMCID: PMC3390465 DOI: 10.1038/ajg.2012.89] [Citation(s) in RCA: 171] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2011] [Accepted: 03/06/2012] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The objective of this study was to analyze the safety of long-term infliximab treatment, with/without concomitant immunomodulators, across Crohn's disease (CD) and ulcerative colitis (UC) clinical trials. METHODS To maximize sample size, we pooled primary safety data across 10 CD or UC trials, including five randomized, controlled trials contributing data from patients who received intravenous infliximab 5 or 10 mg/kg (n=1,713; ±azathioprine) or placebo (n=406; ±azathioprine). Pooled incidences and 95% confidence intervals (CIs) were determined for mortality, infection, and malignancy. Standardized incidence ratios and 95% CIs were also determined for malignancies using the Surveillance, Epidemiology, and End Results database. RESULTS We observed no increase in infections, serious infections, or malignancy with infliximab vs. placebo in these patients with inflammatory bowel disease (IBD). In patients with UC, but not CD, immunomodulator treatment (vs. treatment without immunomodulator) yielded a higher incidence (95% CI) of infections (120.07 (110.66, 130.08)/100 patient-years (pt-yrs) vs. 92.47 (84.54, 100.94)/100 pt-yrs). Among placebo-treated patients with CD, but not UC, those with immunomodulator use demonstrated a higher incidence (95% CI) of malignancy vs. no immunomodulator treatment (1.84 (0.22, 6.66)/100 pt-yrs vs. 0.00 (0.00, 0.00)/100 pt-yrs). Mortality and infection-related mortality appeared unaffected by infliximab or immunomodulator treatment. CONCLUSIONS Infliximab treatment of IBD did not appear to affect incidences of infection, mortality, or malignancy. Relative to patients with no immunomodulator use, immunomodulator-treated UC patients demonstrated a higher incidence of infection and immunomodulator-plus-placebo-treated CD patients demonstrated a higher incidence of malignancy.
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Affiliation(s)
- Gary R Lichtenstein
- Division of Gastroenterology, Hospital of The University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
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Biancone L, Zuzzi S, Ranieri M, Petruzziello C, Calabrese E, Onali S, Ascolani M, Zorzi F, Condino G, Iacobelli S, Pallone F. Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: a single-center cohort study. J Crohns Colitis 2012; 6:578-87. [PMID: 22398047 DOI: 10.1016/j.crohns.2011.11.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2011] [Revised: 10/23/2011] [Accepted: 11/09/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. METHODS In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. RESULTS IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). CONCLUSIONS Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer.
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Affiliation(s)
- Livia Biancone
- Cattedra di Gastroenterologia e Bioinformatica, Università Tor Vergata, Roma, Italy
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Caprioli F, Caruso R, Sarra M, Pallone F, Monteleone G. Disruption of inflammatory signals by cytokine-targeted therapies for inflammatory bowel diseases. Br J Pharmacol 2012; 165:820-8. [PMID: 21806600 DOI: 10.1111/j.1476-5381.2011.01614.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Gut inflammation occurring in patients with inflammatory bowel diseases (IBD) is associated with an excessive immune response that is directed against constituents of the normal bacterial flora and results in the production of large amounts of inflammatory cytokines. Anti-cytokine compounds, such as the neutralizing TNF antibodies, have been employed with clinical success in patients with IBD. However, nearly half of IBD patients are refractory to such treatments, response can wane with time, and anti-TNF treatment can associate with severe side effects and/or development/exacerbation of extra-intestinal immune-mediated pathologies. These observations, and the demonstration that, in IBD, the pathological process is also characterized by defects in the production and/or activity of counter-regulatory cytokines, have boosted further studies aimed at delineating novel strategies to combat the IBD-associated tissue-damaging immune response.
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Affiliation(s)
- Flavio Caprioli
- Unit of Gastroenterology 2, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy
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Rojas-Feria M, Eslam M, Castro-Fernández M, Guerrero P, Larraona-Moreno JL, Romero-Gómez M. Cutaneous lymphoma in a patient with ulcerative colitis after immunosuppressive therapy. J Crohns Colitis 2011; 5:608-11. [PMID: 22115382 DOI: 10.1016/j.crohns.2011.04.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2011] [Revised: 04/12/2011] [Accepted: 04/20/2011] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Biologics are generally safe and well tolerated. However, the risk of haematopoietic cancer in patients with inflammatory bowel disease receiving infliximab has been a growing concern. CASE PRESENTATION We report the first case of cutaneous lymphoma after short use of infliximab in 75-year old Caucasian man with a 7-year history of ulcerative colitis. CONCLUSION Our current knowledge is not sufficient to rule out an increased risk of lymphoma associated with biologics, or allow definitive conclusions to be drawn about the association of infliximab and lymphoma. However, this case and others direct the attention to that both higher index of suspicion and closer follow up are required if patients are maintained on long-term infliximab together with other immunosuppressive therapy.
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Affiliation(s)
- Maria Rojas-Feria
- Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Ctra de Cadiz s/n, Sevilla 41014, Spain.
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Subramaniam K, Tucker K, Craft P, Pavli P. Should patients be screened for hereditary cancer syndromes before starting anti-TNF-α therapy? Inflamm Bowel Dis 2011; 17:E151-2. [PMID: 21987302 DOI: 10.1002/ibd.21883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Accepted: 08/08/2011] [Indexed: 12/09/2022]
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Pham T, Bachelez H, Berthelot JM, Blacher J, Bouhnik Y, Claudepierre P, Constantin A, Fautrel B, Gaudin P, Goëb V, Gossec L, Goupille P, Guillaume-Czitrom S, Hachulla E, Huet I, Jullien D, Launay O, Lemann M, Maillefert JF, Marolleau JP, Martinez V, Masson C, Morel J, Mouthon L, Pol S, Puéchal X, Richette P, Saraux A, Schaeverbeke T, Soubrier M, Sudre A, Tran TA, Viguier M, Vittecoq O, Wendling D, Mariette X, Sibilia J. TNF alpha antagonist therapy and safety monitoring. Joint Bone Spine 2011; 78 Suppl 1:15-185. [PMID: 21703545 DOI: 10.1016/s1297-319x(11)70001-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To develop and/or update fact sheets about TNFα antagonists treatments, in order to assist physicians in the management of patients with inflammatory joint disease. METHODS 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several experts and the overall process was coordinated by three experts. RESULTS Several topics of major interest were selected: contraindications of TNFα antagonists treatments, the management of adverse effects and concomitant diseases that may develop during these therapies, and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA and SpA, initiation and monitoring of TNFα antagonists treatments, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information. CONCLUSION These TNFα antagonists treatments fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on these therapies. They will be available continuously at www.cri-net.com and updated at appropriate intervals.
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Affiliation(s)
- Thao Pham
- Rheumatology Department, CHU Sainte-Marguerite, Marseille, France.
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The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: safety. Am J Gastroenterol 2011; 106:1594-602; quiz 1593, 1603. [PMID: 21844919 DOI: 10.1038/ajg.2011.211] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This paper in the series from the World Congress of Gastroenterology addresses the safety and immunogenicity of biological therapy. The safety profile in randomized controlled studies of all biological agents in Crohn's disease (CD) and ulcerative colitis has been generally favorable, but a small percentage of patients experience severe side effects on biological therapy, including pneumonia, tuberculosis, lymphoma, demyelination, drug-induced lupus, or hepatotoxicity. Although there is unequivocal evidence of an increased risk of serious infection among patients with rheumatoid arthritis treated with anti-tumor necrosis factor therapy, the evidence is less clear in CD. The risk of infection may be increased by combination therapy with steroids and/or immunomodulators. There is a specific risk of the rare γ δ hepatosplenic lymphoma that appears to have a predeliction for young males on combination therapy. The α4 integrin antagonist natalizumab also carries a specific risk of progressive multifocal leucoencephalopathy and reactivation of JC virus infection. The immunogenicity of biological therapy is complex: all agents are potentially immunogenic and this can be reduced by combination with immunomodulators. This may enhance both therapeutic efficacy and the risk of infection or malignancy, so the balance of risk and benefit must be judged for individual patients.
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Angelucci E, Cesarini M, Vernia P. Nonmelanoma skin cancers in four IBD patients on treatment with immunosuppressive agents. Inflamm Bowel Dis 2011; 17:1827-9. [PMID: 21744439 DOI: 10.1002/ibd.21609] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2010] [Accepted: 11/15/2010] [Indexed: 12/09/2022]
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Behm BW, Bickston SJ. Efficacy of infliximab for luminal and fistulizing Crohn's disease and in ulcerative colitis. ACTA ACUST UNITED AC 2011; 10:171-7. [PMID: 17547855 DOI: 10.1007/s11938-007-0010-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Infliximab is arguably the first major advance in therapy for inflammatory bowel disease in more than a quarter of a century. Although it is important to distinguish efficacy from effectiveness, the data from clinical practice mirror those from randomized controlled trials. Infliximab has proven efficacious for luminal manifestations of Crohn's disease (CD) regardless of location. It also has proven efficacy in the subset of penetrating disease to the skin and perianal area, and it increases rates of steroid-free remission. These benefits are reflected in improved quality of life, with limited data showing that infliximab can decrease rates of hospitalization and CD-related surgery. Infliximab also has proven to be efficacious in patients with ulcerative colitis (UC) and has increased rates of steroid-free remission. Whether infliximab will have an impact on the risk of colorectal cancer in UC and Crohn's colitis has yet to be determined. The combination of strong evidence from large randomized controlled trials with substantial examination of use in the practice setting has moved biologic therapy with infliximab from novel to mainstream. In this review, the data for the efficacy of infliximab in controlled trials will be discussed in the context of real world effectiveness.
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Affiliation(s)
- Brian W Behm
- Stephen J. Bickston, MD University of Virginia Digestive Health Center of Excellence, 800708 UVAHS, Charlottesville, VA 22908, USA.
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Abstract
UNLABELLED Assessment of the long-term safety of anti-tumour necrosis factor therapies is vital for the safe treatment of inflammatory bowel disease, a disease affecting a young cohort of patients. AIMS The aim of this retrospective study was to assess the safety and long-term outcome of infliximab use in clinical practice in our institution on an intention to treat basis over the 10-year period from December 1998 to 31 December 2008. METHODS All cases receiving infliximab for ulcerative colitis or Crohn's disease over a 10-year period were identified from hospital pharmacy records. The study was based on a single centre cohort, with an unselected patient group. RESULTS A total of 271 patients were identified as receiving infliximab for either Crohn's disease or ulcerative colitis over the 10-year study period. In total, 2169 infusions were given to the patient cohort. Fifty adverse events led to discontinuation of infliximab therapy in 47 cases. Two patients stopped due to neurological complications. There were six malignancies diagnosed within the cohort during the study period. Four of these were diagnosed while the individual was receiving Infliximab and two occurred at an interval of 21-52 months post their final infliximab infusion. A total of five deaths (1.5%) were observed during the study period. CONCLUSION Infliximab therapy seems to be safe and efficacious in the long term. Although the development of malignancy remains a concern, we have not seen an increased risk of serious infection within our cohort.
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Everett SM, Hamlin PJ. Evidence-based use of anti-TNFα therapy in Crohn's disease; where are we in 2011? Frontline Gastroenterol 2011; 2:144-150. [PMID: 28839599 PMCID: PMC5517221 DOI: 10.1136/fg.2010.003566] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/07/2011] [Indexed: 02/04/2023] Open
Abstract
The efficacy of anti-tumour necrosis factor (anti-TNFα) therapy with infliximab and adalimumab in moderate to severe Crohn's disease has now been proved. This article reviews the evidence supporting best practice with these agents in the light of recent National Institute for Health and Clinical Excellence guidance. Recent studies point to greater efficacy when these drugs are used early in the disease, particularly when mucosal healing can be achieved. For infliximab, the combination with immunomodulator drugs appears to afford greater efficacy, but possibly at the expense of the risk of rare but serious side effects. Patients should be selected carefully for treatment based on prognostic factors predicting aggressive disease, on the one hand, and comorbid factors that might predict side effects, on the other. Multiple drug combinations should be avoided where possible. Finally, a minority of patients in stable remission with complete mucosal healing may be selected for anti-TNFα drug withdrawal.
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Affiliation(s)
- S M Everett
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - P J Hamlin
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Abstract
Management of patients with inflammatory rheumatic disease and a history of (or even a current) malignant disease poses some particular challenges. As direct evidence of the risk of (recurrent or de novo) malignancy in patients with a history of malignant disease is scarce, such a risk may be estimated indirectly from the principal carcinogenicity of the respective drug to be used or (also indirectly) from cancer reactivation data from the transplant literature. In general, cancer risk is increased in patients receiving combination immunosuppressive treatment, but the risk in patients receiving individual drugs (with the exception of alkylating agents) remains entirely unclear. Indirect evidence supports the intuitive concept that the risk of cancer decreases over time after a successful cancer treatment. The only two studies in rheumatic patients with a cancer history were small and have not been able to show an increase in cancer reactivation. The risk of reactivation also depends on the site and location of the prior malignancy. In conclusion, the decision to treat a patient with a history of cancer immunosuppressively should be shared by the rheumatologist and the oncologist. Once the decision is established, such patients need intensive and close monitoring.
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Affiliation(s)
- Katarzyna Elandt
- Division of Oncology, Department of Internal Medicine 1, Medical University Vienna, Austria
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Biancone L, Petruzziello C, Orlando A, Kohn A, Ardizzone S, Daperno M, Angelucci E, Castiglione F, D'Incà R, Zorzi F, Papi C, Meucci G, Riegler G, Sica G, Rizzello F, Mocciaro F, Onali S, Calabrese E, Cottone M, Pallone F. Cancer in Crohn's Disease patients treated with infliximab: a long-term multicenter matched pair study. Inflamm Bowel Dis 2011; 17:758-66. [PMID: 20684009 DOI: 10.1002/ibd.21416] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The long-term risk of neoplasia in Crohn's disease (CD) patients treated with infliximab is undefined. The aim was to assess, in a multicenter, matched-pair study, whether infliximab use in CD is associated with an increased frequency of neoplasia in the long term. METHODS A multicenter, long-term, matched-pair study was conducted in 12 referral inflammatory bowel disease (IBD) centers. An initial cohort of 808 CD patients, including 404 infliximab-treated (CD-IFX) and 404 matched CD controls never treated with infliximab (CD-C) studied from 1999 to 2004, was followed up for an additional 4 years (2004-2008). Cases and controls were matched for: sex, age (±5 years), CD site, follow-up (±5 years), immunosuppressant use, and CD duration (±5 years). From 1999 to 2008 the frequency and characteristics of neoplasia were compared between CD-IFX and CD-C. RESULTS In 2008, 591 patients (304 CD-IFX, 287 CD-C) were in follow-up. Matched couples included 442 patients: 221 CD-IFX and 221 CD-C (median follow-up, months: 72, range 48-114 versus 75, range 44-114). From 1999 to 2008 the frequency of neoplasia among the 591 patients did not differ between CD-IFX (12/304; 3.94%) and CD-C (12/287; 4.19%; P = 0.95). A comparable frequency of neoplasia was also observed between the 221 matched couples (CD-IFX: 8/221; 3.61% versus CD-C: 9/221; 4.07%; P = 1). No specific histotype of cancer appeared associated with infliximab use. CONCLUSIONS The frequency of neoplasia was comparable in an adult population of CD patients treated or not with infliximab, matched for clinical variables and followed up for a median of 6 years.
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De Bie CI, Hummel TZ, Kindermann A, Kokke FTM, Damen GM, Kneepkens CMF, Van Rheenen PF, Schweizer JJ, Hoekstra JH, Norbruis OF, Tjon A Ten WE, Vreugdenhil AC, Deckers-Kocken JM, Gijsbers CFM, Escher JC, De Ridder L. The duration of effect of infliximab maintenance treatment in paediatric Crohn's disease is limited. Aliment Pharmacol Ther 2011; 33:243-50. [PMID: 21083595 DOI: 10.1111/j.1365-2036.2010.04507.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Infliximab is effective for induction and maintenance of remission in children with moderately to severely active Crohn's disease (CD). AIM To evaluate the long-term efficacy of infliximab treatment in paediatric CD. METHODS In this observational, multicentre study, all paediatric CD patients in The Netherlands treated with infliximab from October 1992 to November 2009 and with minimal follow-up of 3 months since start of infliximab, were studied. RESULTS One hundred and fifty-two CD patients [81M; median age at start of infliximab 15.0 years (IQR 13.1-16.4)] received a median number of 10.5 infliximab infusions (IQR 6-21). Median follow-up after start of infliximab was 25 months (IQR 13-40). Kaplan-Meier analysis showed that the cumulative probability of losing response to infliximab in patients who initially required repeated infusions was 13%, 40% and 50% after 1, 3 and 5 years, respectively. Seventy-four patients (49%) needed dose adjustments, with a median time to any adjustment of 6 months. CONCLUSIONS Duration of effect of infliximab is limited as 50% of patients on infliximab maintenance treatment lose their therapeutic response after 5 years. Dose adjustments after start of infliximab are frequently needed to regain therapeutic benefit. These findings emphasise the need for effective, long-term treatment strategies for paediatric CD.
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Affiliation(s)
- C I De Bie
- Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
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Hepatosplenic T-cell lymphoma and inflammatory bowel disease. J Crohns Colitis 2010; 4:511-22. [PMID: 21122554 DOI: 10.1016/j.crohns.2010.05.006] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2010] [Revised: 05/19/2010] [Accepted: 05/19/2010] [Indexed: 02/08/2023]
Abstract
OBJECTIVE This article reviews the current literature and knowledge about hepatosplenic T-cell lymphoma (HSTCL), providing an overview of the clinical features, a description of its pathology and immunophenotypic traits in relation to other lymphomas. In addition, we explore the history of reported cases of hepatosplenic T-cell lymphoma in relation to the possible existence of a causal relationship between infliximab use and HSTCL. The treatments for HSTCL will be briefly addressed. METHODS A comprehensive literature search using multiple databases was performed. Keyword search phrases including "lymphoma," "hepatosplenic T-cell lymphoma," "Inflammatory bowel disease," "6-mercaptopurine," and "infliximab" were used in various combinations. In addition references from published papers were reviewed as well. RESULTS There are over 200 reported cases of HSTCL. Only 22 cases of hepatosplenic T-cell lymphoma are associated with IBD treatment. Clinicians usually reserve immunomodulators and biologics for moderate to severe IBD cases. The ultimate goal of therapy is to control inflammation and therefore allow mucosal healing. IBD patients demonstrating mucosal healing are less likely to undergo surgery and experience complications related to their disease. We manipulate the immune system with corticosteroids, immunomodulators, and biologics, therefore causing bone marrow suppression. With bone marrow suppression, malignant degeneration may begin through selective uncontrolled cell proliferation, initiating HSTCL development in the genetically susceptible. CONCLUSION Hepatosplenic T-cell lymphoma is a rare disease, often with a poor outcome. With the increasing number of reported cases of HSTCL linked to the use of infliximab, adalimumab, and AZA/6-MP, there appears to be an undeniable association of HSTCL development with the use of these agents. This risk is unquantifiable. When considering the rarity of cases and the multiple complications with uncontrolled disease, however, the benefit of treatment far outweighs the risk.
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Miehsler W, Novacek G, Wenzl H, Vogelsang H, Knoflach P, Kaser A, Dejaco C, Petritsch W, Kapitan M, Maier H, Graninger W, Tilg H, Reinisch W. A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease. J Crohns Colitis 2010; 4:221-56. [PMID: 21122513 DOI: 10.1016/j.crohns.2009.12.001] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2009] [Accepted: 12/01/2009] [Indexed: 12/15/2022]
Abstract
Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti-TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.
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Affiliation(s)
- W Miehsler
- Department of Internal Medicine 3, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria.
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Emer JJ, Frankel A, Zeichner JA. A practical approach to monitoring patients on biological agents for the treatment of psoriasis. THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY 2010; 3:20-6. [PMID: 20877538 PMCID: PMC2945861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Psoriasis is a chronic, systemic, inflammatory skin condition that manifests predominantly as well-demarcated, erythematous, scaly plaques on the elbows, knees, and scalp. While mild cases (minimal body surface) often respond to various topical treatments and light therapy, patients with extensive disease (larger body surface and possibly joint involvement) may require systemic medications for remission. The development of biological agents provides dermatologists valuable ways to help treat psoriatic disease quite efficiently, but literature regarding the monitoring of patients on biological treatments is sparse. Clinical practice varies widely since there is modest strong evidence to recommend or refute most tests currently recommended by the United States Food and Drug Administration. The purpose of this article is to present a practical approach to monitoring patients on biological therapy based on the most up-to-date literature.
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Affiliation(s)
- Jason J Emer
- Mount Sinai School of Medicine, Department of Dermatology, New York, New York
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Freeman HJ, Perry T, Webber DL, Chang SD, Loh MY. Mucinous carcinoma in Crohn’s disease originating in a fistulous tract. World J Gastrointest Oncol 2010; 2:307-10. [PMID: 21160662 PMCID: PMC2999135 DOI: 10.4251/wjgo.v2.i7.307] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2009] [Revised: 02/10/2010] [Accepted: 02/17/2010] [Indexed: 02/05/2023] Open
Abstract
Malignant disease, including mucinous carcinomas of the colorectum, may complicate long-standing Crohn’s disease. An 18-year-old male with extensive small and large bowel involvement with Crohn’s disease developed recurrent peri-rectal fistulous disease that persisted for more than a decade despite pharmacological and surgical therapy as well as later therapy with biological agents. Eventually, an extensive and difficult-to-detect mucinous carcinoma developed in the fistulous tract. Although fistula cancer is rarely described in Crohn’s disease, use of immunosuppressant and biological agents may play an initiating or exacerbating role in its development or progression. As potent biological agents are frequently used, often to avoid surgical treatment, clinicians should have an increasingly high index of suspicion for this potential complication, especially if fistulous drainage persists and remains refractory to medical therapy.
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Affiliation(s)
- Hugh J Freeman
- Hugh J Freeman, Tom Perry, Douglas L Webber, Silvia D Chang, Mong-Yang Loh, Departments of Medicine (Gastroenterology), Anesthesia, Pharmacology and Therapeutics, Pathology and Radiology, University of British Columbia, Vancouver, BC, V6T 1W5, Canada
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