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Mateu-Arrom L, Puig L. Choosing the right biologic treatment for moderate-to-severe plaque psoriasis: the impact of comorbidities. Expert Rev Clin Pharmacol 2024; 17:363-379. [PMID: 38603464 DOI: 10.1080/17512433.2024.2340552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 03/01/2024] [Indexed: 04/13/2024]
Abstract
INTRODUCTION Psoriasis is a chronic inflammatory skin disease often associated with several comorbidities, such as psoriatic arthritis, inflammatory bowel disease, obesity, diabetes mellitus or cardiovascular diseases, infections, or cancer, among others. With the progressive aging of the population, a growing number of patients with psoriasis can be expected to present multiple comorbidities. Currently, there is a wide range of biological treatments available for moderate to severe psoriasis, including tumor necrosis alpha (TNF) inhibitors, IL12/23 inhibitor, IL17 inhibitors, and IL23 inhibitors. AREAS COVERED This review aims to describe the specific characteristics of these drugs in relation to psoriasis comorbidities, in order to facilitate decision-making in clinical practice. EXPERT OPINION Some of the biological treatments can influence comorbidities, in some cases even improving them. Therefore, comorbidities are a key factor when deciding on one biological treatment over another. The development of new drugs is expanding the therapeutic arsenal for psoriasis. A high level of expertise in the field with a detailed knowledge of the characteristics of every drug is imperative to provide personalized medicine.
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Affiliation(s)
- Laura Mateu-Arrom
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Lluis Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Universitat Autònoma de Barcelona, Barcelona, Spain
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2
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Romiti R, Hirayama ALDS, Porro AM, Gonçalves HDS, Miot LDB, Durães SMB, Marques SA. Infections in the era of immunobiologicals. An Bras Dermatol 2024; 99:167-180. [PMID: 38238209 PMCID: PMC10943328 DOI: 10.1016/j.abd.2023.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 08/15/2023] [Accepted: 08/27/2023] [Indexed: 03/11/2024] Open
Abstract
Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.
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Affiliation(s)
- Ricardo Romiti
- Department of Dermatology, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil
| | | | - Adriana Maria Porro
- Department of Dermatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Heitor de Sá Gonçalves
- State Health Secretariat of Ceará, Centro de Dermatologia Dona Libânia, Fortaleza, CE, Brazil
| | - Luciane Donida Bartoli Miot
- Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
| | - Sandra Maria Barbosa Durães
- Department of Internal Medicine, Dermatology Unit, Faculty of Medicine, Universidade Federal Fluminense, Niterói, RJ, Brazil
| | - Silvio Alencar Marques
- Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
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3
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Strat N, Sattele L, Elston D. A retrospective cohort review of infectious disease findings in patients screened before immunosuppressant therapy. J Am Acad Dermatol 2023; 89:1282-1283. [PMID: 37579840 DOI: 10.1016/j.jaad.2023.07.1033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 07/17/2023] [Accepted: 07/29/2023] [Indexed: 08/16/2023]
Affiliation(s)
- Nicholas Strat
- College of Graduate Studies, Medical University of South Carolina, Charleston, SC.
| | - Lauren Sattele
- College of Graduate Studies, Medical University of South Carolina, Charleston, SC
| | - Dirk Elston
- Department of Dermatology & Dermatologic Surgery, Medical University of South Carolina, Charleston, SC
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4
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Sawada K, Chung H, Softic S, Moreno-Fernandez ME, Divanovic S. The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease. Cell Metab 2023; 35:1852-1871. [PMID: 37939656 PMCID: PMC10680147 DOI: 10.1016/j.cmet.2023.10.009] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 10/13/2023] [Accepted: 10/13/2023] [Indexed: 11/10/2023]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an unabated risk factor for end-stage liver diseases with no available therapies. Dysregulated immune responses are critical culprits of MASLD pathogenesis. Independent contributions from either the innate or adaptive arms of the immune system or their unidirectional interplay are commonly studied in MASLD. However, the bidirectional communication between innate and adaptive immune systems and its impact on MASLD remain insufficiently understood. Given that both innate and adaptive immune cells are indispensable for the development and progression of inflammation in MASLD, elucidating pathogenic contributions stemming from the bidirectional interplay between these two arms holds potential for development of novel therapeutics for MASLD. Here, we review the immune cell types and bidirectional pathways that influence the pathogenesis of MASLD and highlight potential pharmacologic approaches to combat MASLD based on current knowledge of this bidirectional crosstalk.
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Affiliation(s)
- Keisuke Sawada
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
| | - Hak Chung
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Samir Softic
- Department of Pediatrics and Gastroenterology, University of Kentucky, Lexington, KY 40536, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA
| | - Maria E Moreno-Fernandez
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
| | - Senad Divanovic
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
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5
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Hong JJ, Hadeler EK, Mosca ML, Brownstone ND, Bhutani T, Liao WJ. TNF-alpha inhibitors and ustekinumab for the treatment of psoriasis: therapeutic utility in the era of IL-17 and IL-23 inhibitors. JOURNAL OF PSORIASIS AND PSORIATIC ARTHRITIS 2022; 7:79-92. [PMID: 35757187 PMCID: PMC9229820 DOI: 10.1177/24755303211047479] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and co-morbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.
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Affiliation(s)
- Julie J Hong
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Edward K Hadeler
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Megan L Mosca
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Nicholas D Brownstone
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Tina Bhutani
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
| | - Wilson J Liao
- University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center
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6
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Motolese A, Ceccarelli M, Macca L, Li Pomi F, Ingrasciotta Y, Nunnari G, Guarneri C. Novel Therapeutic Approaches to Psoriasis and Risk of Infectious Disease. Biomedicines 2022; 10:biomedicines10020228. [PMID: 35203438 PMCID: PMC8869084 DOI: 10.3390/biomedicines10020228] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 01/12/2022] [Accepted: 01/18/2022] [Indexed: 01/22/2023] Open
Abstract
Psoriasis is a chronic immune-mediated skin and joint disease, with a plethora of comorbidities, characterized by a certain genetic predisposition, and a complex pathogenesis based on the IL-23/IL-17 pathway. There is no doubt that the patients affected by psoriasis are more susceptible to infections as well as that the risk of infection is higher in psoriatic subjects than in the general population. The advent of biotechnological agents on the therapeutic arsenal actually available for the treatment of moderate-to-severe patients, given the fact that the severity of the disease is a predictor of the level of infectious risk, has raised the question of whether these ‘new’ drugs could be considered a safer option and how they can be used in selected cases. Old and newer strategies in cases of chronic infectious conditions are reviewed under the light of clinical trials and other studies present in literature.
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Affiliation(s)
- Alfonso Motolese
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, Messina, Italy C/O A.O.U.P. “Gaetano Martino”, via Consolare Valeria, 1, 98125 Messina, Italy; (A.M.); (L.M.); (F.L.P.)
| | - Manuela Ceccarelli
- Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, University of Catania, Catania, Italy C/O ARNAS “Garibaldi”, “Nesima” Hospital, via Palermo 636, 95122 Catania, Italy;
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Unit of Infectious Diseases, University of Messina, Messina, Italy C/O A.O.U.P. “Gaetano Martino”, via Consolare Valeria, 1, 98125 Messina, Italy
| | - Laura Macca
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, Messina, Italy C/O A.O.U.P. “Gaetano Martino”, via Consolare Valeria, 1, 98125 Messina, Italy; (A.M.); (L.M.); (F.L.P.)
| | - Federica Li Pomi
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, Messina, Italy C/O A.O.U.P. “Gaetano Martino”, via Consolare Valeria, 1, 98125 Messina, Italy; (A.M.); (L.M.); (F.L.P.)
| | - Ylenia Ingrasciotta
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Pharmacology, University of Messina, Messina, Italy C/O A.O.U.P. “Gaetano Martino”, via Consolare Valeria, 1, 98125 Messina, Italy;
| | - Giuseppe Nunnari
- Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, University of Messina, Messina, Italy C/O A.O.U.P. “Gaetano Martino”, via Consolare Valeria, 1, 98124 Messina, Italy;
| | - Claudio Guarneri
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Dermatology, University of Messina, Messina, Italy C/O A.O.U.P. “Gaetano Martino”, via Consolare Valeria, 1, 98125 Messina, Italy
- Correspondence: ; Tel.: +39-090-2212-894; Fax: +39-09-029-27691
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7
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Chen DY, Lin CH, Chen HH, Tang KT. Association of tumor necrosis factor-α inhibitors and liver cirrhosis in patients with rheumatoid arthritis: A nationwide population-based nested case-control study. Int J Rheum Dis 2022; 25:327-334. [PMID: 34994523 DOI: 10.1111/1756-185x.14272] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 11/29/2021] [Accepted: 12/20/2021] [Indexed: 11/29/2022]
Abstract
AIM Results from various studies are controversial regarding long-term hepatic effects of tumor necrosis factor (TNF)-α inhibitors. Here we aimed to investigate the development of liver cirrhosis with TNF-α inhibitors use in patients with rheumatoid arthritis (RA). METHOD This nested case-control study was based on the National Health Insurance Research Database (January 1, 2000 to December 31, 2008) of Taiwan. We identified 559 adult RA patients who developed liver cirrhosis, and 1055 matched control RA patients. TNF-α inhibitors of interest in the study period included adalimumab and etanercept. Multivariate logistic regression analysis for the development of liver cirrhosis with respect to use of TNF-α inhibitors was performed. RESULTS The incidence rate of liver cirrhosis was 274 per 100 000 person-years in newly diagnosed RA patients. We found the use of TNF-α inhibitors was not associated with the development of liver cirrhosis in RA patients (odds ratio 1.02, 95% confidence interval 0.61, 1.70) after adjustment for potential confounders. In addition, the finding was robust to an unobserved confounder. CONCLUSION We found no association between the use of TNF-α inhibitors and development of liver cirrhosis in RA patients.
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Affiliation(s)
- Der-Yuan Chen
- Translational Medicine Laboratory, China Medical University Hospital, Taichung, Taiwan.,Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Ching-Heng Lin
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Hsin-Hua Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.,Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.,Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.,Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.,Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan
| | - Kuo-Tung Tang
- Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.,Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.,Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
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8
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Febbraio MA, Karin M. "Sweet death": Fructose as a metabolic toxin that targets the gut-liver axis. Cell Metab 2021; 33:2316-2328. [PMID: 34619076 PMCID: PMC8665123 DOI: 10.1016/j.cmet.2021.09.004] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/30/2021] [Accepted: 09/09/2021] [Indexed: 02/07/2023]
Abstract
Glucose and fructose are closely related simple sugars, but fructose has been associated more closely with metabolic disease. Until the 1960s, the major dietary source of fructose was fruit, but subsequently, high-fructose corn syrup (HFCS) became a dominant component of the Western diet. The exponential increase in HFCS consumption correlates with the increased incidence of obesity and type 2 diabetes mellitus, but the mechanistic link between these metabolic diseases and fructose remains tenuous. Although dietary fructose was thought to be metabolized exclusively in the liver, evidence has emerged that it is also metabolized in the small intestine and leads to intestinal epithelial barrier deterioration. Along with the clinical manifestations of hereditary fructose intolerance, these findings suggest that, along with the direct effect of fructose on liver metabolism, the gut-liver axis plays a key role in fructose metabolism and pathology. Here, we summarize recent studies on fructose biology and pathology and discuss new opportunities for prevention and treatment of diseases associated with high-fructose consumption.
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Affiliation(s)
- Mark A Febbraio
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
| | - Michael Karin
- Department of Pharmacology, School of Medicine, University of California, San Diego, San Diego, CA, USA.
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Majerowski J, Gordon KB. Tumor Necrosis Factor Inhibitors. COMPREHENSIVE DERMATOLOGIC DRUG THERAPY 2021:287-301.e7. [DOI: 10.1016/b978-0-323-61211-1.00026-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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10
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Ladda M, Lynde C, Fleming P. Severe Acute Respiratory Syndrome Coronavirus 2 and the Use of Biologics in Patients With Psoriasis. J Cutan Med Surg 2020; 24:625-632. [PMID: 32757760 DOI: 10.1177/1203475420945234] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Coronavirus disease (COVID-19), a respiratory disease caused by a novel coronavirus designated severe acute respiratory syndrome coronavirus 2, has rapidly spread worldwide and has been recognized as a pandemic by the World Health Organization. Patients with altered immunologic function are at higher risk of acquiring COVID-19. In patients with psoriasis, inhibition of select pro-inflammatory cytokines through the use of biologic agents has been shown to be an effective treatment option. Pro-inflammatory cytokines have key immunomodulatory effects and are known to be involved in the hosts' immune response to a variety of viral infections. Though little is currently known about the role of inflammatory cytokines in COVID-19, early reports have shown patients with severe disease to have elevated serum levels of select inflammatory cytokines such as tumor necrosis factor alpha. This review will summarize key information that is currently known about COVID-19, the role of select cytokines in viral defense, and important considerations for patients with psoriasis using biologic agents during this pandemic. Currently, there is insufficient evidence to discontinue biologic therapy in patients with psoriasis who have not tested positive for COVID-19. The decision to pause biologic therapy should be considered on a case-by-case basis in patients in higher risk populations, and should take into account individual risk and benefit. Until more is known about the impact of biologic therapy on COVID-19 outcomes, we recommend patients with psoriasis who test positive for COVID-19 be instructed to discontinue or postpone biologic treatment until they have recovered from infection.
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Affiliation(s)
- Matthew Ladda
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Charles Lynde
- Lynde Institute for Dermatology, Markham, ON, Canada
- 210484 Division of Dermatology, Department of Medicine, University of Toronto, Toronto ON, Canada
| | - Patrick Fleming
- Lynde Institute for Dermatology, Markham, ON, Canada
- 210484 Division of Dermatology, Department of Medicine, University of Toronto, Toronto ON, Canada
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11
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Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies. Clin Microbiol Rev 2020; 33:e00035-19. [PMID: 32522746 PMCID: PMC7289788 DOI: 10.1128/cmr.00035-19] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
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Affiliation(s)
- Joshua S Davis
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David Ferreira
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Emma Paige
- Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia
| | - Craig Gedye
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia
| | - Michael Boyle
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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12
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Sacchelli L, Magnano M, Loi C, Patrizi A, Bardazzi F. The unforeseen during biotechnological therapy for moderate-to-severe psoriasis: How to manage pregnancy and breastfeeding, infections from Mycobacterium tuberculosis, hepatitis B virus, hepatitis C virus, and HIV, surgery, vaccinations, diagnosis of malignancy, and dose tapering. Dermatol Ther 2020; 33:e13411. [PMID: 32291848 DOI: 10.1111/dth.13411] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 03/02/2020] [Accepted: 04/10/2020] [Indexed: 01/01/2023]
Abstract
The use of biotechnological therapies for moderate-to-severe psoriasis is ever-expanding and it is becoming increasingly more frequent to encounter different unforeseen events during their use, such as fertile patients becoming pregnant and breastfeeding, development of infections due to personal habits like tuberculosis, hepatitis B virus, hepatitis C virus, or HIV, scheduling of surgical procedures, need of vaccinations, development of malignancy, and evaluation of dose tapering. As any clinician may experience at least one of these unexpected events, it should be good practice to know how to manage them. Thus, a practical analysis has been proposed in this study.
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Affiliation(s)
- Lidia Sacchelli
- Department of Specialized, Clinical and Experimental Medicine, Division of Dermatology, University of Bologna, Bologna, Italy
| | - Michela Magnano
- Department of Specialized, Clinical and Experimental Medicine, Division of Dermatology, University of Bologna, Bologna, Italy
| | - Camilla Loi
- Department of Specialized, Clinical and Experimental Medicine, Division of Dermatology, University of Bologna, Bologna, Italy
| | - Annalisa Patrizi
- Department of Specialized, Clinical and Experimental Medicine, Division of Dermatology, University of Bologna, Bologna, Italy
| | - Federico Bardazzi
- Department of Specialized, Clinical and Experimental Medicine, Division of Dermatology, University of Bologna, Bologna, Italy
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13
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Tang KT, Dufour JF, Chen PH, Hernaez R, Hutfless S. Antitumour necrosis factor-α agents and development of new-onset cirrhosis or non-alcoholic fatty liver disease: a retrospective cohort. BMJ Open Gastroenterol 2020; 7:e000349. [PMID: 32377366 PMCID: PMC7199652 DOI: 10.1136/bmjgast-2019-000349] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/23/2019] [Accepted: 12/06/2019] [Indexed: 12/16/2022] Open
Abstract
Objective Elevated tumour necrosis factor (TNF)-α has been implicated in the progression of liver fibrosis and pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aim to investigate the impact of anti-TNF-α agents on the development of cirrhosis and NAFLD. Design This retrospective cohort study used a US claims database between 1 January 2010 and 31 December 2016. We identified adult patients with ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis or rheumatoid arthritis. Anti-TNF-α agents of interest included adalimumab, certolizumab, etanercept, golimumab and infliximab. The primary composite outcome was the development of new-onset cirrhosis, NAFLD or non-alcoholic steatohepatitis (NASH). The secondary outcomes were the development of (1) cirrhosis and (2) NAFLD or NASH. Propensity score for anti-TNF-α agent use was generated by logistic regression. Cox proportional hazard models adjusting for the propensity score were used with regard to time-varying anti-TNF-α agent exposure. Results This study included 226 555 incident patients with immune-related diseases. During the median 1.5 years follow-up, there was an increased hazard with anti-TNF-α agent use in regard to liver outcomes (composite outcome HR: 1.47, 95% CI 1.27 to 1.70; cirrhosis HR 1.47, 95% CI 0.96 to 2.23; NAFLD or NASH HR 1.53, 95% CI 1.32 to 1.77). The composite outcome hazard was increased for each immune-related disease (HR 1.25–1.90). Conclusion In the short term, we did not observe a beneficial effect of anti-TNF-α agent use for development of cirrhosis, NAFLD or NASH in patients with immune-related diseases.
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Affiliation(s)
- Kuo-Tung Tang
- Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jean-François Dufour
- Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, Bern, Switzerland.,Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Po-Hung Chen
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ruben Hernaez
- Section of Gastroenterology, Michael E DeBakey VA Medical Center, Houston, Texas, USA.,Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA
| | - Susan Hutfless
- Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Priora M, Realmuto C, Parisi S, Ditto MC, Borrelli R, Peroni CL, Laganà A, Fusaro E. Rheumatologic manifestations of hepatitis C in the era of direct-acting antiviral agents. MINERVA GASTROENTERO 2020; 66:280-289. [PMID: 32218427 DOI: 10.23736/s1121-421x.20.02680-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Beyond the classic hepatic complications, hepatitis C (HCV) infection is considered as a systemic disease, since extrahepatic manifestations become clinically evident in 40% to 70% of the patients and it can frequently include rheumatic ones. Furthermore, HCV can promote the production of several autoantibodies, thus complicating the differential diagnosis between primitive and HCV-related rheumatic disorders. The recent development of direct-acting antivirals (DAA) against HCV has revolutionized the field, reducing the damage stemming from systemic inflammatory phenomena and persistent immune activation associated with continuous HCV replication. Our review focuses on the main rheumatologic manifestations associated with chronic HCV infection as well as the impact of DAA interferon-free treatments on such extrahepatic clinical involvement.
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Affiliation(s)
- Marta Priora
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy -
| | - Cristina Realmuto
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Simone Parisi
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Maria C Ditto
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Richard Borrelli
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Clara L Peroni
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Angela Laganà
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Enrico Fusaro
- Division of Rheumatology, Città della Salute e della Scienza, University of Turin, Turin, Italy
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Campanati A, Diotallevi F, Martina E, Paolinelli M, Radi G, Offidani A. Safety update of etanercept treatment for moderate to severe plaque psoriasis. Expert Opin Drug Saf 2020; 19:439-448. [PMID: 32178543 DOI: 10.1080/14740338.2020.1740204] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) for patients with psoriasis are often linked to inadequate outcomes and risk of multiple adverse effects. Biologic agents such as etanercept (ETN) have revolutionized the therapeutic management of psoriasis, allowing the treatment of most difficult cases, and fragile patients.Areas covered: The authors searched PubMed using the term 'psoriasis,' 'etanercept,' and 'safety.' Articles considered by the authors to be most relevant, such as randomized controlled studies, cohort studies, and review articles placing emphasis on studies of efficacy and safety were selected. Case reports and letters relating to safety were also included. The main sources of data referenced by these articles were also included in the review. Besides, to get the relevant studies, the reference lists were examined to identify the potentially available studies. The aim of this review is to describe the safety profile of ETN, used for psoriasis treatment, focusing on related clinical implications.Expert opinion: ETN has a favorable safety profile, and its use should be largely considered in psoriatic patients. Caution should be recommended in case of chronic heart failure, autoimmune disease, previous malignancies, familial history of demyelinating diseases, latent TBC infection, chronic HBV and HCV infection or HIV.
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Affiliation(s)
- Anna Campanati
- Dermatological Clinic, Department of Clinical and Molecular Sciences, Polytechnic Marche University, Ancona, Italy
| | - Federico Diotallevi
- Dermatological Clinic, Department of Clinical and Molecular Sciences, Polytechnic Marche University, Ancona, Italy
| | - Emanuela Martina
- Dermatological Clinic, Department of Clinical and Molecular Sciences, Polytechnic Marche University, Ancona, Italy
| | - Matteo Paolinelli
- Dermatological Clinic, Department of Clinical and Molecular Sciences, Polytechnic Marche University, Ancona, Italy
| | - Giulia Radi
- Dermatological Clinic, Department of Clinical and Molecular Sciences, Polytechnic Marche University, Ancona, Italy
| | - Annamaria Offidani
- Dermatological Clinic, Department of Clinical and Molecular Sciences, Polytechnic Marche University, Ancona, Italy
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Chiu YM, Chen DY. Infection risk in patients undergoing treatment for inflammatory arthritis: non-biologics versus biologics. Expert Rev Clin Immunol 2020; 16:207-228. [PMID: 31852268 DOI: 10.1080/1744666x.2019.1705785] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Despite the therapeutic effectiveness of biologics targeting immune cells or cytokines in patients with inflammatory arthritis, which reflects their pathogenic roles, an increased infection risk is observed in those undergoing biological treatment. However, there are limited data regarding the comparison of infection risks in inflammatory arthritis patients treated with non-biologics (csDMARDs), biologics (bDMARDs), including tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors, or targeted synthetic (ts)DMARDs.Areas covered: Through a review of English-language literature as of 30 June 2019, we focus on the existing evidence on the risk of infections caused by bacteria, Mycobacterium tuberculosis, and hepatitis virus in inflammatory arthritis patients undergoing treatment with csDMARDs, bDMARDs, or tsDMARDs.Expert opinion: While the risks of bacterial and mycobacterial infection are increased in arthritis patients treated with csDMARDs, the risks are further higher in those receiving bDMARDs therapy, particularly TNF inhibitors. Regarding HBV infection, antiviral therapy may effectively prevent HBV reactivation in patients receiving bDMARDs, especially rituximab. However, more data are needed to establish effective preventive strategies for HBsAg-negative/HBcAb-positive patients. It seems safe to use cyclosporine and TNF inhibitors in patients with HCV infection, while those undergoing rituximab therapies should be frequently monitored for HCV activity.Abbreviations: ABT: abatacept; ADA: adalimumab; AS: ankylosing spondylitis; bDMARDs: biologic disease-modifying anti-rheumatic drugs; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; CS: corticosteroids; CsA: cyclosporine A; csDMARDs: conventional synthetic disease-modifying anti-rheumatic drugs; CZP: certolizumab; DAAs: direct-acting antiviral agents; DM: diabetes mellitus; DOT: directly observed therapy; EIN: Emerging Infections Network; ETN: etanercept; GOL: golimumab; GPRD: General Practice Research Database; HBV: hepatitis B virus; HBVr: HBV reactivation; HBsAg+: HBsAg-positive; HBsAg-/anti-HBc+: HBsAg-negative anti-HBc antibodies-positive; HCV: hepatitis C virus; HCQ: hydroxychloroquine: IFX: infliximab; IL-6: interleukin-6; JAK: Janus kinase; LEF: leflunomide; LTBI: latent tuberculosis infection; mAb: monoclonal antibody; MTX: methotrexate; OR: odds ratio; PsA: psoriatic arthritis; PMS: post-marketing surveillance; RA: rheumatoid arthritis; TNF: tumor necrosis factor; TNFi: tumor necrosis factor inhibitor; SCK: secukinumab; SSZ: sulfasalazine; TOZ: tocilizumab; RCT: randomized controlled trial; RR: relative risk; RTX: rituximab; 3HP: 3-month once-weekly isoniazid plus rifapentine; TB: tuberculosis; tsDMARDs: targeted synthetic disease-modifying anti-rheumatic drugs; UTK: ustekinumab; WHO: World Health Organization.
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Affiliation(s)
- Ying-Ming Chiu
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Der-Yuan Chen
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan.,Translational Medicine Laboratory, Rheumatic Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.,Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.,Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
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17
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Piaserico S, Messina F, Russo FP. Managing Psoriasis in Patients with HBV or HCV Infection: Practical Considerations. Am J Clin Dermatol 2019; 20:829-845. [PMID: 31222626 DOI: 10.1007/s40257-019-00457-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Considered more efficacious and safer than traditional systemic drugs, biologic therapies have dramatically improved the quality of life of patients with psoriasis. Recently, there has been a proliferation of new targeted treatment options, including anti-interleukin-17, anti-interleukin-12/23, as well as small-molecule drugs such as apremilast. There are nevertheless some concerns regarding their use, especially in patients with chronic infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). It has been estimated that two billion individuals are infected with HBV worldwide and approximately 240 million have chronic HBV infection. Moreover, there are approximately 71 million individuals with chronic HCV infection worldwide, with a high percentage of them unaware of being infected. As patients with HBV and HCV infections are excluded from controlled clinical trials investigating new drugs, data regarding their safety in patients with psoriasis are based almost exclusively on case reports and small retrospective cohort studies and need to be constantly updated. The risk of HBV reactivation can be defined as: high risk (≥ 10%), moderate risk (1-10%), and low risk (< 1%) depending on the type of immunosuppressive therapy stratified by the presence or absence of hepatitis B surface antigen but positivity to anti-hepatitis B core antigen. Hepatitis B surface antigen-positive patients treated with tumor necrosis factor-α inhibitors, ustekinumab, or cyclosporine carry a high or moderate risk of HBV reactivation and should be considered candidates for prophylactic anti-HBV therapy. Once therapy is commenced, it is important to check HBV DNA levels every 3 months. Hepatitis B virus reactivation typically occurs with immune reconstitution and therefore antiviral therapy should continue for 6-12 months after stopping immunosuppression. Hepatitis B surface antigen-positive patients who are prescribed methotrexate, acitretin, or apremilast have a low risk and need to be monitored for viral reactivation by determining alanine aminotransferase and HBV DNA levels every 3 months. No conclusive data are available for interleukin-17 and interleukin-23 inhibitors. Anti-hepatitis B core antigen-positive patients treated with tumor necrosis factor-α inhibitors, ustekinumab, and cyclosporine are linked to a moderate risk of reactivation, and they should preferably undergo HBV DNA or hepatitis B surface antigen and alanine aminotransferase testing rather than be subjected to routine pre-emptive therapy. Anti-hepatitis B core antigen-positive patients receiving methotrexate, acitretin, or apremilast have a low risk of reactivation and do not require anti-HBV therapy, nor should monitoring be considered mandatory. No conclusive data are available for interleukin-17 and interleukin-23 inhibitors.
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Affiliation(s)
- Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padova, Via Cesare Battisti 206, 35128, Padua, Italy.
| | - Francesco Messina
- Dermatology Unit, Department of Medicine, University of Padova, Via Cesare Battisti 206, 35128, Padua, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
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18
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Chularojanamontri L, Nimanong S, Wongpraparut C, Silpa-Archa N, Chaiyabutr C, Charoenpipatsin N. How do we treat psoriasis patients with hepatitis C infections in real-world situations? A retrospective analysis of 34 patients. J DERMATOL TREAT 2019; 32:321-327. [PMID: 31418622 DOI: 10.1080/09546634.2019.1657225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND There is still relatively limited data on psoriasis and hepatitis C virus (HCV) infections. OBJECTIVE This study investigated the clinical characteristics and treatment of psoriasis patients with HCV infections in real-world practice. METHODS Medical records of all psoriasis patients with HCV infections who attended the outpatient clinic at Siriraj Hospital over a 10-year period were retrospectively reviewed. RESULTS Of 34 patients, 26 and 8 patients were men and women, respectively with a mean age of 57.0 ± 8.7 (range, 42.2-77.2) years. The median age of psoriasis onset was 42.7 ± 12.7 (range, 8-67.25) years. With a median follow-up period of 13.6 years, cirrhosis and hepatocellular carcinoma were found in 67.6% and 29.4% of the patients, respectively. The interferon used for HCV treatment exacerbated the psoriasis in 20% of those patients. Conventional treatments and anti-tumor necrosis factors (anti-TNFs) were used in strict collaboration with hepatologists. No patients experienced a worsening of their HCV infection. CONCLUSION Despite a limited number of patients, a male predominance and late-onset psoriasis were frequently observed. Although, interferon therapy for HCV can exacerbate psoriasis, it is not contraindicated. All conventional treatments and anti-TNFs can be used, provided that there is strict collaboration with hepatologists.
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Affiliation(s)
- Leena Chularojanamontri
- Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Supot Nimanong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chanisada Wongpraparut
- Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Narumol Silpa-Archa
- Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chayada Chaiyabutr
- Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Norramon Charoenpipatsin
- Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Murdaca G, Negrini S, Pellecchio M, Greco M, Schiavi C, Giusti F, Puppo F. Update upon the infection risk in patients receiving TNF alpha inhibitors. Expert Opin Drug Saf 2019; 18:219-229. [PMID: 30704314 DOI: 10.1080/14740338.2019.1577817] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 01/30/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION TNF-α inhibitors can be administered either as monotherapy or in combination with other anti-inflammatory drugs or DMARDs in the treatment of chronic immune-mediated diseases. AREAS COVERED Patients receiving TNF-α inhibitors are at high risk of infections. An update is made on the risk of infection in patients receiving TNF-α inhibitors and the strategies for mitigating against the development of these serious adverse events. EXPERT OPINION Infliximab than etanercept appears to be responsible for the increased risk of infections. Re-activation of latent tuberculosis infection and the overall risk of opportunistic infections should be considered before beginning a course of TNF-α inhibitors. A careful medical history, Mantoux test/quantiferon-TB Gold In-tube Test and chest-X-ray should always be performed before starting TNF-α inhibitors. Particular attention should be paid to risk factors for Pneumocystis jirovecii infection. Hepatitis B and C virological follow-up should be considered during TNF-α inhibitors treatment. Finally, appropriate vaccinations for influenza, S. pneumoniae, and HBV should be administered to decrease the risk of infection, and patients who are at high risk of herpes zoster reactivation would benefit from a second vaccination in adulthood.
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Affiliation(s)
- Giuseppe Murdaca
- a Clinical Immunology Unit, Department of Internal Medicine , University of Genoa and Ospedale Policlinico San Martino , Genoa , Italy
| | - Simone Negrini
- a Clinical Immunology Unit, Department of Internal Medicine , University of Genoa and Ospedale Policlinico San Martino , Genoa , Italy
| | - Marco Pellecchio
- a Clinical Immunology Unit, Department of Internal Medicine , University of Genoa and Ospedale Policlinico San Martino , Genoa , Italy
| | - Monica Greco
- a Clinical Immunology Unit, Department of Internal Medicine , University of Genoa and Ospedale Policlinico San Martino , Genoa , Italy
| | - Chiara Schiavi
- a Clinical Immunology Unit, Department of Internal Medicine , University of Genoa and Ospedale Policlinico San Martino , Genoa , Italy
| | - Francesca Giusti
- a Clinical Immunology Unit, Department of Internal Medicine , University of Genoa and Ospedale Policlinico San Martino , Genoa , Italy
| | - Francesco Puppo
- a Clinical Immunology Unit, Department of Internal Medicine , University of Genoa and Ospedale Policlinico San Martino , Genoa , Italy
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20
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Sebastiani M, Milazzo L, Atzeni F, Vacchi C, Manfredi A, Quartuccio L, Scirè C, Gaeta GB, Lapadula G, Armignacco O, Tavio M, D'Angelo S, Meroni P, Bazzichi L, Grassi W, Mathieu A, Mastroianni C, Sagnelli E, Santantonio T, Foppa CU, Puoti M, Sarmati L, Airò P, Epis OM, Scrivo R, Gargiulo M, Riva A, Ciancio G, Zehender G, Taliani G, Meroni L, Sollima S, Sarzi-Puttini P, Galli M. Italian consensus recommendations for the management of hepatitis C infection in patients with rheumatoid arthritis. Mod Rheumatol 2019; 29:895-902. [PMID: 30582388 DOI: 10.1080/14397595.2018.1558918] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown.Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations.Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice.Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and InnovationsHCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs).HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8-12 weeksConventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.
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Affiliation(s)
- Marco Sebastiani
- Rheumatology Unit, Department of Medical and Surgical Science, University of Modena, Azienda Policlinico of Modena, Modena, Italy
| | - Laura Milazzo
- Infectious Diseases Unit, University of Milano, Luigi Sacco Hospital, Milan, Italy
| | - Fabiola Atzeni
- Rheumatology Unit, L. Sacco University Hospital, Milan, Italy
| | - Caterina Vacchi
- Rheumatology Unit, Department of Medical and Surgical Science, University of Modena, Azienda Policlinico of Modena, Modena, Italy
| | - Andreina Manfredi
- Rheumatology Unit, Department of Medical and Surgical Science, University of Modena, Azienda Policlinico of Modena, Modena, Italy
| | - Luca Quartuccio
- Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy
| | - Carlo Scirè
- Epidemiology Unit, Italian Society for Rheumatology (SIR), Milan, Italy
| | - Giovanni Battista Gaeta
- Infectious Diseases and Viral Hepatitis Unit, Department of Internal and Specialistic Medicine, Second University of Naples, Naples, Italy
| | - Giovanni Lapadula
- Department of Medicine - Rheumatology Unit, Medical School, University of Bari, Bari, Italy
| | | | - Marcello Tavio
- Unit of Emerging and Immunosuppressed Infectious Diseases, Department of Gastroenterology and Transplantation, Azienda Ospedaliero-Universitaria "Ospedali Riuniti", Torrette Ancona, Italy
| | - Salvatore D'Angelo
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy
| | - Pierluigi Meroni
- Division of Rheumatology, Department of Clinical Sciences and Community Health, Gaetano Pini Orthopedic Institute, University of Milan, Milan, Italy
| | - Laura Bazzichi
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Walter Grassi
- Department of Rheumatology, Università Politecnica delle Marche, Ospedale "C. Urbani", Jesi Ancona, Italy
| | - Alessandro Mathieu
- Rheumatology Unit, University Clinic and AOU of Cagliari, Cagliari, Italy
| | - Claudio Mastroianni
- Infectious Diseases Unit, Department Public Health and Infectious Disease, "Sapienza" University of Rome, Rome, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | | | - Caterina Uberti Foppa
- Department of Infectious Diseases, San Raffaele Scientific Institute, Università Vita-Salute, Milan, Italy
| | - Massimo Puoti
- Department of Infectious Diseases, AO Niguarda Ca' Granda, Milano, Italy
| | - Loredana Sarmati
- Clinical Infectious Diseases, Tor Vergata University, Rome, Italy
| | - Paolo Airò
- Rheumatology and Clinical Immunology Unit, Spedali Civili of Brescia, Brescia, Italy
| | | | - Rossana Scrivo
- Department of Internal Medicine and Medical Specialties-Rheumatology Unit, Sapienza University of Rome, Rome, Italy
| | - Miriam Gargiulo
- Third Department of Infectious Diseases- D. Cotugno Hospital- AORN dei Colli, Naple, Italy
| | - Agostino Riva
- Rheumatology Unit, L. Sacco University Hospital, Milan, Italy
| | - Giovanni Ciancio
- Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Sant'Anna University Hospital, Ferrara, Italy
| | | | - Gloria Taliani
- Infectious Diseases Unit, Department Public Health and Infectious Disease, "Sapienza" University of Rome, Rome, Italy
| | - Luca Meroni
- Rheumatology Unit, L. Sacco University Hospital, Milan, Italy
| | | | | | - Massimo Galli
- Rheumatology Unit, L. Sacco University Hospital, Milan, Italy
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Psoriasis: Which therapy for which patient. J Am Acad Dermatol 2019; 80:43-53. [DOI: 10.1016/j.jaad.2018.06.056] [Citation(s) in RCA: 169] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 05/24/2018] [Accepted: 06/01/2018] [Indexed: 12/17/2022]
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Wroński J, Fiedor P. The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought? J Clin Pharmacol 2018; 59:445-462. [PMID: 30476367 DOI: 10.1002/jcph.1348] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 10/27/2018] [Indexed: 12/12/2022]
Abstract
Tumor necrosis factor (TNF) inhibitors significantly improved the treatment options for patients with ankylosing spondylitis. Unfortunately, currently, there is no strategy for sustaining remission of the disease with TNF inhibitors; after discontinuation, a high percentage of patients experience flares in a short time. Therefore, up-to-date, long-term use of TNF inhibitors in patients with ankylosing spondylitis remains necessary. For this reason, the issue of the long-term safety of TNF inhibitors in patients with ankylosing spondylitis raises concerns. Although TNF inhibitors are well established in ankylosing spondylitis treatment, the majority of studies on TNF inhibitors' safety have been performed in patients with rheumatoid arthritis. Until recently, there were very few studies of TNF inhibitors' safety in ankylosing spondylitis. Meanwhile, TNF inhibitors appear to have different safety profiles in ankylosing spondylitis and rheumatoid arthritis. In this review, we describe available data on the occurrence of adverse events associated with TNF inhibitor treatment in ankylosing spondylitis, including serious adverse events, infections, serious infections, tuberculosis, opportunistic infections, hepatitis B reactivation, malignancies, laboratory test abnormalities, autoimmune diseases, paradoxical adverse events, and heart failure.
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Affiliation(s)
- Jakub Wroński
- Department of Rheumatology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.,Department of Disaster Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Fiedor
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
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Lopetuso LR, Mocci G, Marzo M, D'Aversa F, Rapaccini GL, Guidi L, Armuzzi A, Gasbarrini A, Papa A. Harmful Effects and Potential Benefits of Anti-Tumor Necrosis Factor (TNF)-α on the Liver. Int J Mol Sci 2018; 19:E2199. [PMID: 30060508 PMCID: PMC6121684 DOI: 10.3390/ijms19082199] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 07/19/2018] [Accepted: 07/24/2018] [Indexed: 02/08/2023] Open
Abstract
Anti-tumor necrosis factor (TNF)-α agents represent an effective treatment for chronic inflammatory diseases. However, some concerns about their potentially undesirable effects on liver function have been reported. On the other hand, evidence of their therapeutic effects on certain liver diseases is accumulating. Many data showed the safety of anti-TNF-α in patients with chronic hepatitis B and C and in liver transplanted patients even if a strict follow-up and prophylaxis are recommended in well-defined subgroups. On the other side, anti-TNF-α-induced liver injury is not a rare event. However, it is often reversible after anti-TNF-α withdrawal. Anti-TNF-α agents have been tested in advanced stages of severe alcoholic hepatitis and non-alcoholic fatty liver disease. Limited data on the efficacy of anti-TNF-α in patients with autoimmune hepatitis and primary biliary cholangitis are also available. In this review, we explored the hepatic safety concerns in patients receiving anti-TNF-α agents with and without pre-existent hepatic diseases. In addition, the available evidence on their potential benefits in the treatment of specific hepatic diseases is discussed.
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Affiliation(s)
- Loris Riccardo Lopetuso
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Giammarco Mocci
- Gastroenterology Unit, Brotzu Hospital, 09121 Cagliari, Italy.
| | - Manuela Marzo
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Francesca D'Aversa
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Gian Lodovico Rapaccini
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Luisa Guidi
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Alessandro Armuzzi
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Alfredo Papa
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
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ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents). Clin Microbiol Infect 2018; 24 Suppl 2:S10-S20. [DOI: 10.1016/j.cmi.2017.12.025] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 12/25/2017] [Accepted: 12/30/2017] [Indexed: 12/14/2022]
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Murdaca G, Negrini S, Magnani O, Penza E, Pellecchio M, Gulli R, Mandich P, Puppo F. Update upon efficacy and safety of etanercept for the treatment of spondyloarthritis and juvenile idiopathic arthritis. Mod Rheumatol 2018; 28:417-431. [PMID: 28837372 DOI: 10.1080/14397595.2017.1366006] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 08/01/2017] [Indexed: 02/08/2023]
Abstract
TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis (AS), psoriasis (Ps) and/or psoriatic arthritis (PsA) and may be administered off-label to treat disseminated granuloma annulare, systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this article, we discuss the efficacy and safety of etanercept in the treatment of spondyloarthritis and juvenile idiopathic arthritis (JIA). Etanercept is effective in the treatment of PsA, AS, JIA and uveitis. Independent predictors of achieving a sustained clinical improvement or MDA in children with JIA include shorter disease duration, no concurrent oral corticosteroid use, history of chronic anterior uveitis and age <9 years. IBD incidence was lower in patients receiving etanercept plus MTX. Intra-articular administration of etanercept seems to favor a prompt target joint improvement without serious adverse events. Etanercept improve endothelial function reducing the risk of acute cardiovascular and/or cerebrovascular events. The most commonly reported adverse events were nasopharyngitis, epidermal and dermal conditions, upper respiratory tract infection, cough, headache and fatigue.
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Affiliation(s)
- Giuseppe Murdaca
- a Department of Internal Medicine, Scleroderma Unit, Clinical Immunology Unit , University of Genova and IRCCS-Azienda Ospedaliera Universitaria San Martino , Genova , Italy
| | - Simone Negrini
- a Department of Internal Medicine, Scleroderma Unit, Clinical Immunology Unit , University of Genova and IRCCS-Azienda Ospedaliera Universitaria San Martino , Genova , Italy
| | - Ottavia Magnani
- a Department of Internal Medicine, Scleroderma Unit, Clinical Immunology Unit , University of Genova and IRCCS-Azienda Ospedaliera Universitaria San Martino , Genova , Italy
| | - Elena Penza
- a Department of Internal Medicine, Scleroderma Unit, Clinical Immunology Unit , University of Genova and IRCCS-Azienda Ospedaliera Universitaria San Martino , Genova , Italy
| | - Marco Pellecchio
- a Department of Internal Medicine, Scleroderma Unit, Clinical Immunology Unit , University of Genova and IRCCS-Azienda Ospedaliera Universitaria San Martino , Genova , Italy
| | - Rossella Gulli
- b Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, Section of Medical Genetics , University of Genova and IRCCS-Azienda Ospedaliera Universitaria San Martino , Genova , Italy
| | - Paola Mandich
- b Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, Section of Medical Genetics , University of Genova and IRCCS-Azienda Ospedaliera Universitaria San Martino , Genova , Italy
| | - Francesco Puppo
- a Department of Internal Medicine, Scleroderma Unit, Clinical Immunology Unit , University of Genova and IRCCS-Azienda Ospedaliera Universitaria San Martino , Genova , Italy
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Routhouska SB, Korman NJ. Initiating and Monitoring Patients on Biologic Therapy for Psoriasis beyond the FDA: Our more Cautious Approach. ACTA ACUST UNITED AC 2018. [DOI: 10.1177/247553030612a00105] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Biologics are offering new hope for patients with moderate to severe chronic plaque psoriasis and psoriatic arthritis, and every day more dermatologists are prescribing these medications for their patients. Prior to prescribing a biologic it is important to conduct the proper screening to determine if your patient is an appropriate candidate. While patients are being treated with biologics they need to be monitored carefully to maximize the benefit of the agent and minimize harmful side effects. Apart from the recommendations and requirements of the U.S. Food and Drug Administration (FDA), there are as yet no consensus statements or guidelines addressing the appropriate approach to initiating and monitoring patients being treated with biologics. In this article we will discuss our own approach to initiating and monitoring that we believe is appropriate for patients being treated with biologics. Our recommendations, which in many ways go beyond the recommendations and requirements of the FDA, should not be interpreted as the standard of care.
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Affiliation(s)
- Shannon B. Routhouska
- Clinical Research Fellow Department of Dermatology Case Western Reserve University University Hospitals of Cleveland
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Carrascosa JM, Del-Alcazar E. New therapies versus first-generation biologic drugs in psoriasis: a review of adverse events and their management. Expert Rev Clin Immunol 2018; 14:259-273. [DOI: 10.1080/1744666x.2018.1454835] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- J. M. Carrascosa
- Department of Dermatology, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
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28
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Park KS. Chronic Hepatitis C Virus Infection, Why Not Treat Now? JOURNAL OF RHEUMATIC DISEASES 2018. [DOI: 10.4078/jrd.2018.25.3.151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Kyung-Su Park
- Division of Rheumatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Piaserico S, Dapavo P, Conti A, Gisondi P, Russo FP. Adalimumab is a safe option for psoriasis patients with concomitant hepatitis B or C infection: a multicentre cohort study of 37 patients and review of the literature. J Eur Acad Dermatol Venereol 2017; 31:1853-1859. [PMID: 28146345 DOI: 10.1111/jdv.14146] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Accepted: 01/16/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Little data are available about the safety of TNF-α inhibitors in patients with HCV and HBV infection. In particular, data concerning the use of adalimumab in patients with psoriasis and concomitant viral hepatitis are lacking and little is known about the drug's real safety in this context. OBJECTIVE To assess the long-term safety of adalimumab in a group of 17 consecutive psoriatic patients affected by chronic HBV infection and 20 consecutive psoriatic patients affected by chronic HCV infection. METHODS Thirty-seven consecutive patients with psoriasis and concomitant HBV or HCV infection being treated with adalimumab at four Italian referral centres (Modena, Padova, Verona and Turin) were assessed before the treatment and at the end of follow-up. Viral load and radiological studies (echography, Fibroscan) were also carried out in some of the patients. RESULTS The patients responded well to treatment and did not show any HBV or HCV reactivation in a mean follow-up period of 27 and 40 months, respectively. The fibrosis score in eight HCV patients showed a slight reduction: pretreatment mean value 5.83 and post-treatment mean value 5.65. CONCLUSION The use of adalimumab seems to be safe in patients with severe psoriasis and HBV or HCV infection. Nevertheless, large-scale prospective studies will be able to provide vital information on the impact of anti-TNF treatment on hepatic function in patients with psoriasis and concomitant chronic HCV or HBV infection and appropriate monitoring scheduling.
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Affiliation(s)
- S Piaserico
- Dermatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | - P Dapavo
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy
| | - A Conti
- Dermatology Unit, Department of Medicine and Medical Specialties, University of Modena, Modena, Italy
| | - P Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - F P Russo
- Gastroenterology Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
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Abdulaziz S, Halabi H, Omair MA, Attar S, Alghamdi A, Shabrawishi M, Neyazi A, Alnazzawi H, Meraiani N, Almoallim H. Biological therapy in arthritis patients with hepatitis B or C infection: a multicenter retrospective case series. Eur J Rheumatol 2017; 4:194-199. [PMID: 29164002 PMCID: PMC5685275 DOI: 10.5152/eurjrheum.2017.17003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 04/10/2017] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE Reactivation of viral hepatitis B (HBV) and C (HCV) has been reported in various case reports of patients with arthritis on biological therapy. The objective of this study was to describe the clinical characteristics and outcomes of arthritis patients with HBV or HCV treated with biological therapy. MATERIAL AND METHODS This is a retrospective case series including all patients above 13 years of age with arthritis patients from four centers in Saudi Arabia with concurrent chronic viral hepatitis infection (HBV or HCV) who received biological agents in the rheumatology clinics during their course of their disease from duration of the disease onset until last outpatient visit up to November 2015. Demographic information, full details about the hepatitis status of each patient, rheumatic disease diagnosis and different therapies used were reviewed. RESULTS We identified 10 cases each with HBV and HCV on biological therapy. The mean age in the HBV group was 51 (34-85) years and 80% were females. Eight patients had rheumatoid arthritis (RA), one patient had RA/systemic lupus erythematosus, and one had human immunodeficiency virus related-arthritis. Seven were chronic inactive HBsAg carriers and three had chronic active HBV. Nine HBV patients received prophylactic antiviral therapy. Two cases with chronic HBV had reactivation with no elevation of the transaminases.The mean age in the HCV group was 54 (23-79) years and all were female RA patients. Three had detectable hepatitis C virus-ribonuecleic acid (HCV-RNA) before the start of biological therapy. Nine HCV patients received antiviral treatment and seven had a sustained virologic response (SVR) before start of biological treatment. Three patients had detectable HCV-RNA during the course of biological therapy. One of the three was a non-responder and two were relapsers. One of the patients with HCV relapse was started on sofosbuvir plus ribavirin and achieved SVR on follow-up. CONCLUSION We report the successful use of biological therapy in arthritis patients with hepatitis B infection with antiviral therapy with no detoriation of their viral status. Due to the lack of sufficient prospective studies demonstrating the rate of HCV flare on biological therapy, caution should be exercised and careful monitoring with liver enzymes and viral load is mandated in vulnerable HCV RNA patients. Treatment should be individualized by the rheumatologist in collaboration with the hepatologist to minimize complications.
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Affiliation(s)
- Sultana Abdulaziz
- Unit of Rheumatology, Department of Medicine, King Fahd Hospital, Jeddah, Saudi Arabia
| | - Hussein Halabi
- Department of Medicine, King Faisal Specialist Hospital, Jeddah, Saudi Arabia
| | - Mohammed A. Omair
- Division of Rheumatology, Department of Medicine, King Saud University College of Medicine, Riyadh, Saudi Arabia
| | - Suzan Attar
- Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdullah Alghamdi
- Unit of Gastroenterology, Department of Medicine, King Fahd Hospital, Jeddah, Saudi Arabia
| | | | - Abdulwahab Neyazi
- Department of Medicine, Umm Alqura University School of Medicine, Makkah, Saudi Arabia
| | - Haneen Alnazzawi
- Department of Medicine, Umm Alqura University School of Medicine, Makkah, Saudi Arabia
| | - Nuha Meraiani
- Department of Medicine, King Faisal Specialist Hospital, Jeddah, Saudi Arabia
| | - Hani Almoallim
- Department of Medicine, Umm Alqura University School of Medicine, Makkah, Saudi Arabia
- Department of Medicine, Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia
- Alzaidi Chair of Research Diseases, Umm Alqura University School of Medicine, Makkah, Saudi Arabia
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31
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Kim HB, Myung SK, Lee YJ, Park BJ. Efficacy of vitamin D supplementation in combination with conventional antiviral therapy in patients with chronic hepatitis C infection: a meta-analysis of randomised controlled trials. J Hum Nutr Diet 2017; 31:168-177. [PMID: 28833855 DOI: 10.1111/jhn.12503] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Although a contributory role of vitamin D levels for the development of chronic hepatitis C has been suggested, the efficacy of vitamin D supplementation in combination with conventional antiviral therapy consisting of pegylated interferon-α (Peg-IFN-α) injection and oral ribavirin (RBV) remains unclear. We investigated its efficacy in the treatment of chronic hepatitis C via a meta-analysis of randomised controlled trials. METHODS We searched PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and the bibliographies of relevant articles to locate additional publications in September 2016. Three evaluators independently reviewed and selected eligible studies based on predetermined selection criteria. RESULTS Of 522 articles meeting our initial criteria, a total of seven open-label, randomised controlled trials involving 548 participants, were included in the final analysis. Vitamin D supplementation in combination with Peg-IFN-α injection and oral RBV significantly increased the rate of viral response for hepatitis C at 24 weeks after treatment in a random-effects meta-analysis (relative risk = 1.30; 95% confidence interval = 1.04-1.62; I2 = 75.9%). Also, its significant efficacy was observed in patients with hepatitis C virus genotype 1, which is known to be refractory to antiviral therapy. CONCLUSIONS In summary, we observed that additional use of vitamin D has a positive effect on sustained viral response rates of patients with chronic hepatitis C infection. However, we cannot establish the efficacy because of substantial heterogeneity, a small sample size and a low methodological quality.
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Affiliation(s)
- H-B Kim
- Department of Family Medicine, MyongJi Hospital, Goyang, Gyeonggi-do, Korea.,Department of Family Medicine, School of Medicine, Yonsei University, Seoul, Korea
| | - S-K Myung
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Gyeonggi-do, Korea.,Cancer Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang, Korea.,Department of Family Medicine, Center for Cancer Prevention and Detection, Hospital, National Cancer Center, Goyang, Korea
| | - Y-J Lee
- Department of Family Medicine, School of Medicine, Yonsei University, Seoul, Korea.,Department of Family Medicine, Gangnam Severance Hospital, Seoul, Korea
| | - B-J Park
- Department of Family Medicine, School of Medicine, Yonsei University, Seoul, Korea.,Department of Family Medicine, Yongin Severance Hospital, Yongin, Gyeonggi-do, Korea
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Noe MH, Grewal SK, Shin DB, Ogdie A, Takeshita J, Gelfand JM. Increased prevalence of HCV and hepatic decompensation in adults with psoriasis: a population-based study in the United Kingdom. J Eur Acad Dermatol Venereol 2017; 31:1674-1680. [PMID: 28485831 DOI: 10.1111/jdv.14310] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 03/27/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUND The hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with conflicting evidence regarding a possible association with psoriasis. OBJECTIVE To determine the prevalence of HCV in psoriasis patients, compared to controls, and to determine the incidence of hepatic decompensation in HCV+ psoriasis patients compared to HCV+ controls. METHODS Cross-sectional and cohort studies were conducted in The Health Improvement Network (THIN). RESULTS In fully adjusted models, a statistically significant increase in prevalence was seen in the adults with psoriasis (OR: 1.24, 95% CI 1.10-1.40). A "dose-response" of HCV prevalence with increasing psoriasis severity was not observed. HCV+ patients with psoriasis had a non-statistically significant increased incidence of hepatic decompensation compared to HCV+ individuals without psoriasis (aHR: 1.58, 95% CI: 0.90-2.77). The risk was highest and statistically significant, in those with moderate-to-severe psoriasis (aHR: 21.51, 95% CI: 7.58-61.03). CONCLUSIONS These results demonstrate a higher prevalence of HCV in adults with psoriasis and a higher rate of hepatic decompensation in HCV+ individuals with moderate-severe psoriasis.
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Affiliation(s)
- M H Noe
- Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - S K Grewal
- Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - D B Shin
- Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA.,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA
| | - A Ogdie
- Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.,Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - J Takeshita
- Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA.,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA
| | - J M Gelfand
- Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA.,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA
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Burton MJ, Curtis JR, Yang S, Chen L, Singh JA, Mikuls TR, Winthrop KL, Baddley JW. Safety of Biologic and Nonbiologic Disease-modifying Antirheumatic Drug Therapy in Veterans with Rheumatoid Arthritis and Hepatitis C Virus Infection. J Rheumatol 2017; 44:565-570. [DOI: 10.3899/jrheum.160983] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2017] [Indexed: 12/12/2022]
Abstract
Objective.To examine the effect of disease-modifying antirheumatic drug (DMARD) therapy on hepatotoxicity among patients with rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection.Methods.We identified biologic and nonbiologic treatment episodes of patients with RA using the 1997–2011 national data from the US Veterans Health Administration. Eligible episodes had HCV infection (defined by detectable HCV RNA) and subsequently initiated a new biologic or nonbiologic DMARD. Cohort entry required a baseline alanine aminotransferase (ALT) < 66 IU/l and quantifiable HCV RNA within 90 days prior to starting biologic/DMARD therapy. The primary outcome of interest was hepatotoxicity, defined as ALT elevation ≥ 100 IU/l or increase in HCV RNA of 1 log or more, and was examined within the first year of biologic/DMARD use. Results were reported as the cumulative incidence of treatment episodes achieving predefined hepatotoxicity at 3, 6, and 12 months after biologic/DMARD initiation.Results.RA patients with HCV (n = 748) were identified and contributed 1097 biologic/DMARD treatment episodes. Overall, ALT elevations were uncommon, with 37 (3.4%) hepatotoxicity events occurring within 12 months. Treatment episodes with biologic DMARD demonstrated more frequency of hepatotoxicity than did nonbiologic DMARD (4.8% vs 2.3%, p = 0.03). Among treatment episodes involving hepatotoxicity events, the majority occurred within 6 months of DMARD initiation (29/37, 78%).Conclusion.In US veterans with HCV and RA receiving biologic and nonbiologic DMARD, the frequency of hepatotoxicity (ALT ≥ 100 IU/l) was low, with a higher frequency observed in treatment episodes with current biologic use.
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Rodríguez de Santiago E, Albillos Martínez A, López-Sanromán A. Infections in inflammatory bowel disease. Med Clin (Barc) 2017; 148:415-423. [PMID: 28233560 DOI: 10.1016/j.medcli.2016.12.041] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 12/17/2016] [Accepted: 12/24/2016] [Indexed: 02/07/2023]
Abstract
Patients with inflammatory bowel disease constitute a population with a special predisposition to develop bacterial, viral and fungal infections. Iatrogenic immunosuppression, frequent contact with healthcare facilities and surgical interventions are some of the risk factors that explain why these infections are one of the main causes of morbi-mortality in this disease. Some of these infections follow a subtle and paucisymptomatic evolution; their diagnosis and management may become a real challenge for the attending physician if their screening is not systematized or they are not considered in the differential diagnosis. The objective of this review is to provide an update from a practical and concise perspective on the knowledge regarding the epidemiology, prevention, diagnosis and treatment of the most common infections.
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Affiliation(s)
| | - Agustín Albillos Martínez
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Madrid, España; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá de Henares, Alcalá de Henares, Madrid, España
| | - Antonio López-Sanromán
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Madrid, España; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá de Henares, Alcalá de Henares, Madrid, España
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Degasperi E, Caprioli F, El Sherif O, Back D, Colombo M, Aghemo A. Challenges in treating patients with inflammatory bowel disease and concurrent viral hepatitis infection. Expert Rev Gastroenterol Hepatol 2016; 10:1373-1383. [PMID: 27718758 DOI: 10.1080/17474124.2016.1246181] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel diseases (IBD) require long-term administration of immunomodulatory treatments to maintain disease remission. Due to the high worldwide prevalence of hepatitis B (HBV) or C (HCV) virus infections, presence of concurrent hepatitis can be a relevant clinical issue to manage when treating IBD. Areas covered: The paper summarizes epidemiological data about IBD and HBV/HCV infection and reviews current knowledge about the natural history of HBV and HCV in the IBD setting, concentrating on risk of hepatitis reactivation during immunosuppressive treatment. Most updated recommendations for management of HBV and HCV infections in IBD patients are discussed. Expert commentary: The development of new drugs for IBD with different molecular targets and the availability of potent and efficacious antiviral drugs for HBV and HCV will simplify management of hepatitis infection in IBD patients in the near future.
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Affiliation(s)
- Elisabetta Degasperi
- a A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology , Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan , Italy
| | - Flavio Caprioli
- b Department of Pathophysiology and Transplantation , Università degli Studi di Milano , Milan , Italy.,c Gastroenterology and Endoscopy Unit , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
| | - Omar El Sherif
- d Gastroenterology Specialist Registrar , St. James's Hospital , Dublin , Ireland.,e Research Fellow, School of Medicine , Trinity College Dublin , Dublin , Ireland
| | - David Back
- f Department of Molecular and Clinical Pharmacology , University of Liverpool , Liverpool , UK
| | - Massimo Colombo
- a A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology , Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan , Italy
| | - Alessio Aghemo
- a A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology , Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan , Italy
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Ooka K, Lim JK. Treatment of Hepatitis C in Patients Undergoing Immunosuppressive Drug Therapy. J Clin Transl Hepatol 2016; 4:206-227. [PMID: 27777889 PMCID: PMC5075004 DOI: 10.14218/jcth.2016.00017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Revised: 06/22/2016] [Accepted: 07/12/2016] [Indexed: 12/09/2022] Open
Abstract
With 185 million people chronically infected globally, hepatitis C is a leading bloodborne infection. All-oral regimens of direct acting agents have superior efficacy compared to the historical interferon-based regimens and are significantly more tolerable. However, trials of both types of regimens have often excluded patients on immunosuppressive medications for reasons other than organ transplantation. Yet, these patients-most often suffering from malignancy or autoimmune diseases-could stand to benefit from these treatments. In this study, we systematically review the literature on the treatment of hepatitis C in these neglected populations. Research on patients with organ transplants is more robust and this literature is reviewed here non-systematically. Our systematic review produced 2273 unique works, of which 56 met our inclusion criteria and were used in our review. The quality of data was low; only 3 of the 56 studies were randomized controlled trials. Sustained virologic response was reported sporadically. Interferon-containing regimens achieved this end-point at rates comparable to that in immunocompetent individuals. Severe adverse effects and death were rare. Data on all-oral regimens were sparse, but in the most robust study, rates of sustained virologic response were again comparable to immunocompetent individuals (40/41). Efficacy and safety of interferon-containing regimens and all-oral regimens were similar to rates in immunocompetent individuals; however, there were few interventional trials. The large number of case reports and case series makes conclusions vulnerable to publication bias. While firm conclusions are challenging, given the dearth of high-quality studies, our results demonstrate that antiviral therapy can be safe and effective. The advent of all-oral regimens offers patients and clinicians greatly increased chances of cure and fewer side effects. Preliminary data reveal that these regimens may confer such benefits in immunosuppressed individuals as well. More prospective interventional trials would greatly benefit the many patients with chronic hepatitis C on immunosuppressive therapies.
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Affiliation(s)
- Kohtaro Ooka
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Joseph K. Lim
- Yale Liver Center, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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Guenther L, Lynde C, Ho V. Practical Considerations for the Initiation and Maintenance of Etanercept in the Treatment of Psoriasis. J Cutan Med Surg 2016. [DOI: 10.2310/7750.2006.00072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Etanercept is a new treatment for moderate to severe psoriasis. In contrast to traditional systemic agents, which can be given orally, etanercept is given by subcutaneous injection. Patient selection, transitioning, dosing, safety, monitoring, duration of therapy, and patient support programs are reviewed.
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Affiliation(s)
- Lyn Guenther
- From the Division of Dermatology, University of Western Ontario, London, ON; The Guenther Dermatology Research Centre, London, ON; University Health Network, University of Toronto, Toronto, ON; Lynde Centre for Dermatology, Markham, ON; and Department of Dermatology, University of British Columbia, Vancouver, BC
| | - Charles Lynde
- From the Division of Dermatology, University of Western Ontario, London, ON; The Guenther Dermatology Research Centre, London, ON; University Health Network, University of Toronto, Toronto, ON; Lynde Centre for Dermatology, Markham, ON; and Department of Dermatology, University of British Columbia, Vancouver, BC
| | - Vincent Ho
- From the Division of Dermatology, University of Western Ontario, London, ON; The Guenther Dermatology Research Centre, London, ON; University Health Network, University of Toronto, Toronto, ON; Lynde Centre for Dermatology, Markham, ON; and Department of Dermatology, University of British Columbia, Vancouver, BC
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Affiliation(s)
- Richard G. Langley
- From the Division of Dermatology, Department of Medicine, Dalhousie University, Halifax, NS; Department of Medicine, University of Toronto, Toronto, ON; The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Toronto, ON; Division of Advanced Therapeutics in Arthritis, Mount Sinai Hospital, Toronto, ON; Division of Dermatology, University of Montreal, Montreal, QC; Innovaderm Research Incorporated, Montreal, QC; Probity Medical Research, Waterloo, ON
| | - Edward C. Keystone
- From the Division of Dermatology, Department of Medicine, Dalhousie University, Halifax, NS; Department of Medicine, University of Toronto, Toronto, ON; The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Toronto, ON; Division of Advanced Therapeutics in Arthritis, Mount Sinai Hospital, Toronto, ON; Division of Dermatology, University of Montreal, Montreal, QC; Innovaderm Research Incorporated, Montreal, QC; Probity Medical Research, Waterloo, ON
| | - Robert Bissonnette
- From the Division of Dermatology, Department of Medicine, Dalhousie University, Halifax, NS; Department of Medicine, University of Toronto, Toronto, ON; The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Toronto, ON; Division of Advanced Therapeutics in Arthritis, Mount Sinai Hospital, Toronto, ON; Division of Dermatology, University of Montreal, Montreal, QC; Innovaderm Research Incorporated, Montreal, QC; Probity Medical Research, Waterloo, ON
| | - Kim A. Papp
- From the Division of Dermatology, Department of Medicine, Dalhousie University, Halifax, NS; Department of Medicine, University of Toronto, Toronto, ON; The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Toronto, ON; Division of Advanced Therapeutics in Arthritis, Mount Sinai Hospital, Toronto, ON; Division of Dermatology, University of Montreal, Montreal, QC; Innovaderm Research Incorporated, Montreal, QC; Probity Medical Research, Waterloo, ON
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Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression. J Virol 2016; 90:5549-5560. [PMID: 27009955 PMCID: PMC4886784 DOI: 10.1128/jvi.02557-15] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 02/29/2016] [Indexed: 12/22/2022] Open
Abstract
Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states. IMPORTANCE Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections. Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses. In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states.
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Abstract
Hepatitis C virus (HCV) infection is a common liver disease worldwide with a high rate of chronicity (75-80%) in infected individuals. The chronic form of HCV leads to steatosis, cirrhosis and hepatocellualr carcinoma. Steatosis is prevalent in HCV patients (55%) due to a combination of viral factors (effect of viral proteins on some of the intracellular pathways) and host factors (overweight, insulin resistance, diabetes mellitus, and alcohol consumption). The response rates to treatment of chronic HCV with pegylated interferon (PEG-IFN) and (in the case of genotype-1 HCV, the most common infecting genotype in the USA) ribavirin (RBV) is low, with a sustained viral response rate ≤ 40%. Adding direct-acting antiviral agents-recently approved by the FDA-to the standard protocol has increased the response rate; however HCV-related end-stage liver disease is still the primary indication for liver transplantation in the USA. The focus of this article is on the interrelation between HCV, steatosis and metabolic syndrome.
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Affiliation(s)
- Jamak Modaresi Esfeh
- Department of Gastroenterology and Hepatology, The Cleveland Clinic, Cleveland, OH, USA
| | - Kianoush Ansari-Gilani
- Department of Radiology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA
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Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O'Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol 2015; 68:1-26. [PMID: 26545940 DOI: 10.1002/art.39480] [Citation(s) in RCA: 1345] [Impact Index Per Article: 134.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 10/14/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
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Affiliation(s)
| | | | | | - Elie A Akl
- American University of Beirut, Beirut, Lebanon, and McMaster University, Hamilton, Ontario, Canada
| | | | | | | | | | | | | | | | | | - Deborah Parks
- Washington University School of Medicine, St. Louis, Missouri
| | | | | | | | - Amye Leong
- Healthy Motivation, Santa Barbara, California
| | | | - John T Schousboe
- University of Minnesota and Park Nicollet Clinic, St. Louis Park
| | | | - Seth Ginsberg
- Global Healthy Living Foundation, New York, New York
| | - James Grober
- NorthShore University Health System, Evanston, Illinois
| | | | | | - Amy S Miller
- American College of Rheumatology, Atlanta, Georgia
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Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O'Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St.Clair EW, Tindall E, Miller AS, McAlindon T. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 2015; 68:1-25. [DOI: 10.1002/acr.22783] [Citation(s) in RCA: 794] [Impact Index Per Article: 79.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 10/14/2015] [Indexed: 12/11/2022]
Affiliation(s)
| | | | | | - Elie A. Akl
- American University of Beirut, Beirut, Lebanon, and McMaster University; Hamilton Ontario Canada
| | | | | | | | | | | | | | | | | | - Deborah Parks
- Washington University School of Medicine; St. Louis Missouri
| | | | | | | | - Amye Leong
- Healthy Motivation; Santa Barbara California
| | | | | | | | | | - James Grober
- NorthShore University Health System; Evanston Illinois
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TNF-α Induced by Hepatitis C Virus via TLR7 and TLR8 in Hepatocytes Supports Interferon Signaling via an Autocrine Mechanism. PLoS Pathog 2015; 11:e1004937. [PMID: 26023919 PMCID: PMC4449221 DOI: 10.1371/journal.ppat.1004937] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 05/06/2015] [Indexed: 02/07/2023] Open
Abstract
Invasion by infectious pathogens can elicit a range of cytokine responses from host cells. These cytokines provide the initial host defense mechanism. In this report, we demonstrate that TNF-α, a pro-inflammatory cytokine, can be induced by hepatitis C virus (HCV) in its host cells in a biphasic manner. The initial induction of TNF-α by HCV was prompt and could be blocked by the antibody directed against the HCV E2 envelope protein and by chemicals that inhibit endocytosis, indicating the specificity of endocytic uptake of HCV in this induction. Further studies indicated that the induction of TNF-α was dependent on toll-like receptors 7 and 8 (TLR7/8) but not on other intracellular pattern recognition receptors. Consistently, siRNA-mediated gene silencing of the downstream effectors in the TLR7/8 signaling pathway including MyD88, IRAK1, TRAF6, TAK1 and p65 NF-κB suppressed the expression of TNF-α. The role of p65 NF-κB in the induction of TNF-α via transcriptional up-regulation was further confirmed by the chromatin immunoprecipitation assay. TNF-α induced by HCV could activate its own receptor TNFR1 on hepatocytes to suppress HCV replication. This suppressive effect of TNF-α on HCV was due to its role in supporting interferon signaling, as the suppression of its expression led to the loss of IFNAR2 and impaired interferon signaling and the induction of interferon-stimulated genes. In conclusion, our results indicate that hepatocytes can sense HCV infection via TLR7/8 to induce the expression of TNF-α, which inhibits HCV replication via an autocrine mechanism to support interferon signaling. Hepatitis C virus (HCV) patients have increased levels of circulating tumor necrosis factor-α (TNF-α). In this report, we demonstrate that HCV can directly induce the expression of TNF-α in hepatocytes in a biphasic manner via NF-κB. The induction of TNF-α by HCV in the first phase is prompt, requires no HCV gene expression and is dependent on TLR7 and TLR8 and their downstream effectors. TNF-α induced by HCV supports interferon signaling via an autocrine mechanism and suppresses HCV replication, as abolishing the expression of TNF-α or its receptor TNFR1 results in the loss of IFNAR2, a subunit of the type I interferon receptor, and an increase of HCV replication. Our studies thus reveal an interesting interplay between HCV and hepatocytes, with the virus attempting to blunt the IFN response by depleting IFNAR2 and the host cell overcoming this blunting effect of HCV by using TNF-α to restore the expression of IFNAR2.
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Caso F, Cantarini L, Morisco F, Del Puente A, Ramonda R, Fiocco U, Lubrano E, Peluso R, Caso P, Galeazzi M, Punzi L, Scarpa R, Costa L. Current evidence in the field of the management with TNF-α inhibitors in psoriatic arthritis and concomitant hepatitis C virus infection. Expert Opin Biol Ther 2015; 15:641-50. [DOI: 10.1517/14712598.2015.1011616] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Selmi C, Ceribelli A, Naguwa SM, Cantarini L, Shoenfeld Y. Safety issues and concerns of new immunomodulators in rheumatology. Expert Opin Drug Saf 2014; 14:389-99. [PMID: 25518908 DOI: 10.1517/14740338.2015.993605] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION The development of biologic therapies has been an enormous leap in the management of patients with rheumatoid and psoriatic arthritis. Since the first anti-TNF-α therapies, numerous molecules have been identified as targets of immunomodulatory therapies, such as IL-1 (anakinra, canakinumab), IL-6 (tocilizumab), CD20(+) B cells (rituximab), CTLA4 (abatacept) and two additional anti-TNF-α therapies (certolizumab pegol, golimumab). AREAS COVERED In the present review, we will describe the safety issues related to the immunosuppressive action of these biologic drugs that are mainly represented by infection and malignancy. The risk of infection should be identified before initiating a biologic treatment and markers checked over time, in particular for tuberculosis and hepatitis B and C viruses. Other infections (bacterial, viral, parasitic; opportunistic; surgery-related) and safety issues may require temporary interruption of the treatment until complete resolution. No significantly increased risk of malignancy, both hematological and solid, has been associated with the use of biologic agents. In all cases, it is difficult to dissect the risks related to biologics from those related to baseline treatments. EXPERT OPINION Detailed medical history and laboratory screening should be performed before starting biologic therapies. Clinicians should be aware of the different safety profiles associated with different molecules and they should follow up data coming out of the existing registries for biologics in regard to new or old side effects.
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Affiliation(s)
- Carlo Selmi
- Humanitas Research Hospital, Division of Rheumatology and Clinical Immunology , Rozzano, Milan , Italy
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Bojito-Marrero L, Pyrsopoulos N. Hepatitis B and Hepatitis C Reactivation in the Biologic Era. J Clin Transl Hepatol 2014; 2:240-246. [PMID: 26355300 PMCID: PMC4548361 DOI: 10.14218/jcth.2014.00033] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Revised: 12/02/2014] [Accepted: 12/08/2014] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B (HBV) and hepatitis C (HCV) reactivation may occur after the use of biologic agents. During the last decade, utilization of biologics has changed the fate of many treated for cancer, autoimmune and connective tissue disease, maintenance of transplanted organs, and the prevention of graft-versus-host disease among others. HBV reactivation has been reported in up to 50% of HBV carriers undergoing immunosuppressive therapy, and there is emerging data pointing towards an increased risk for HCV reactivation. If reactivation of HBV and HCV occurs, the spectrum of clinical manifestations can range from asymptomatic hepatitis flares to hepatic decompensation, fulminant hepatic failure, and death. Therefore, identifying patients at risk and early diagnosis are imperative to decrease significant morbidity and mortality. The purpose of this article is to review the pathophysiology of the reactivation of HBV and HCV infection in patients receiving biologic therapies and the approaches used to diagnose, prevent, and treat HBV and HCV reactivation.
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Affiliation(s)
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, USA
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Vilarrasa E, Puig L. Psoriasis: Biologic treatment and liver disease. World J Dermatol 2014; 3:76-85. [DOI: 10.5314/wjd.v3.i4.76] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Revised: 03/28/2014] [Accepted: 09/17/2014] [Indexed: 02/07/2023] Open
Abstract
Patients with moderate or severe psoriasis have a high prevalence of chronic liver disease. Chronic liver disease in these patients is related to metabolic syndrome, alcohol abuse or viral infections. Therefore, treatment of these patients is challenging. Classic systemic treatments may be contraindicated because of their immunosuppressive and hepatotoxic potential. First-line therapy in this setting is generally ultraviolet B phototherapy combined with topical treatment, but its feasibility and efficacy are sometimes limited. The therapeutic options are further restricted by concomitant psoriatic arthritis. Biologic treatments have shown to be effective in psoriasis and psoriatic arthritis, and they are largely devoid of liver toxicity. Anti-tumor necrosis factor-alpha (TNF-α) treatments have proven to be effective and safe in patients with chronic hepatitis C virus (HCV) infections and other non-infectious chronic liver disorders, including alcoholic and non-alcoholic liver diseases. However, in chronic hepatitis B virus (HBV), anti-TNF-α treatments carry a potential risk of HBV reactivation. Anti-interleukin-12/23 treatments are also effective in patients with psoriasis, but data regarding their safety in chronic hepatitis infections are still limited. Safety reports in patients with psoriasis and chronic HCV infection are contradictory, and in chronic HBV evidence indicate a high risk of viral reactivation. Moreover, concerns remain about the long-term safety of both TNF-α antagonists and ustekinumab. Non-viral liver diseases such as alcoholic and non-alcoholic liver diseases are more prevalent in patients with psoriasis than in the general population. TNF-α antagonists have also been prescribed in these patients. Although data are still scarce in this setting, results suggest a favorable profile in patients with psoriasis and non-alcoholic liver diseases. We review the literature regarding all these aspects.
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Approach and management of patients with chronic hepatitis B and C during the course of inflammatory bowel disease. Inflamm Bowel Dis 2014; 20:2142-50. [PMID: 25072501 DOI: 10.1097/mib.0000000000000126] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease and chronic viral hepatitis are 2 distinct but common conditions throughout the world. Mostly, both need life-long follow-up. Since immunosuppressive drugs remain corner stones of inflammatory bowel disease management, one should be aware of the concomitant presence of chronic viral hepatitis in such patients to prevent serious (even fatal) outcomes. Recently, new treatment options have become available in the treatment of both inflammatory bowel disease and chronic viral hepatitis. In this review, we have discussed and summarized current treatment and follow-up strategies for those 2 important public health issues in light of available literature.
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