scholarly journals Inflammatory bowel disease and drug-induced liver damage

2021 ◽  
pp. 138-146
Author(s):  
G. V. Volynets ◽  
A. I. Khavkin
Keyword(s):  
Liver Damage ◽  
Kinase Inhibitors ◽  
Liver Function Tests ◽  
Janus Kinase ◽  
New Drugs ◽  
Interleukin 12 ◽  
Drug Induced ◽  
Hepatotoxic Effect ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The article presents the results of a review of publications devoted to the study of the problems of drug-induced liver damage in inflammatory bowel diseases (IBD). The hepatotoxic effect of thiopurines (azathioprine and 6-mercaptopurine) — hepatotoxicity from 0% to 17%; sulfasalazine and mesalamine (hepatotoxicity from 0% to 4%); methotrexate (hepatotoxicity from 15% to 50%); tumor necrosis factor inhibitors (hepatotoxicity up to 75% of cases.), anti-integrins (hepatotoxicity from 2% to 5%); an interleukin 12/23 inhibitor (hepatotoxicity from 0,5% to 2%); Janus-kinase inhibitors is considered (hepatotoxicity from 1% to 2%).Conclusion. The drugs currently used to treat IBD require periodic liver function tests to rule out drug-induced lesions that require therapy correction. As the range of new drugs is rapidly expanding, this requires special observation and discussion in terms of their adverse effects on the liver.

Optimizing Immunization Strategies in Patients with IBD

2020 ◽  
Vol 27 (1) ◽  
pp. 123-133 ◽  
Author(s):  
Freddy Caldera ◽  
Dana Ley ◽  
Mary S Hayney ◽  
Francis A Farraye
Keyword(s):  
Kinase Inhibitors ◽  
Mucosal Healing ◽  
Common Adverse Event ◽  
Janus Kinase ◽  
Interleukin 12 ◽  
Vaccine Preventable Diseases ◽  
Immunization Strategies ◽  
The Us ◽  
Inflammatory Bowel ◽  
Adult Immunization

Abstract Recent advances in the treatment of inflammatory bowel disease (IBD) include the use of immune modifiers and monoclonal antibodies, such as tumor necrosis factor (TNF) alpha inhibitors, anti-integrin agents, janus kinase inhibitors, and interleukin-12/23 inhibitors. These agents achieve higher rates of clinical remission and mucosal healing than conventional therapy. However, these therapies increase the risk of infections, including some vaccine-preventable diseases. Infections are one of the most common adverse event of immunosuppressive therapy. Thus, providers should optimize immunization strategies to reduce the risk of vaccine-preventable infections in patients with IBD. There are several newly licensed vaccines recommended for adults by the US Advisory Committee on Immunization Practices. This review will focus on how gastroenterology providers can implement the adult immunization schedule approved by ACIP for patients with IBD.

scholarly journals Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey

2014 ◽  
Vol 7 ◽  
pp. CGast.S13125 ◽  
Author(s):  
Maria Cappello ◽  
Claudia Randazzo ◽  
Ivana Bravatà ◽  
Anna Licata ◽  
Sergio Peralta ◽  
...  
Keyword(s):  
Liver Function ◽  
Fatty Liver ◽  
Inflammatory Bowel Diseases ◽  
Normal Values ◽  
Liver Function Tests ◽  
Gamma Glutamyl Transpeptidase ◽  
Drug Induced ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Altered Liver

Background and Aims Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. Materials and Methods A retrospective review was undertaken of all consecutive IBD in- and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as an increase in aspartate aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), or total bilirubin. Results A cohort of 335 patients (179 males, mean age 46.0 ± 15.6 years) was analyzed. Abnormal LFTs were detected in 70 patients (20.9%). In most cases, the alterations were mild and spontaneously returned to normal values in about 60% of patients. Patients with abnormal LFTs were less frequently on treatment with aminosalicylates (22.8 vs. 36.6%, P = 0.04). The most frequent cause for transient abnormal LFTs was drug-induced cholestasis (34.1%), whereas fatty liver was the most frequent cause of persistent liver damage (65.4%). A cholestatic pattern was found in 60.0% of patients and was mainly related to older age, longer duration of disease, and hypertension. Conclusions The prevalence of LFT abnormalities is relatively high in IBD patients, but the development of severe liver injury is exceptional. Moreover, most alterations of LFTs are mild and spontaneously return to normal values. Drug-induced hepatotoxicity and fatty liver are the most relevant causes of abnormal LFTs in patients with IBD.

scholarly journals The Era of Janus Kinase Inhibitors for Inflammatory Bowel Disease Treatment

2021 ◽  
Vol 22 (21) ◽  
pp. 11322
Author(s):  
Jin-Woo Kim ◽  
Su-Young Kim
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kinase Inhibitors ◽  
Significant Proportion ◽  
Janus Kinase ◽  
Response To Treatment ◽  
Interleukin 12 ◽  
Disease Treatment ◽  
Janus Kinase Inhibitors ◽  
Inflammatory Bowel

For a significant proportion of patients with inflammatory bowel disease (IBD), primary non-response and secondary loss of response to treatment remain significant issues. Anti-tumor necrosis factor therapies have been licensed for use in IBD. Other disease-related pathways have been targeted as well, including the interleukin 12/23 axis and lymphocyte tracking. However, the need for parenteral administration and the associated costs of dispensing and monitoring all biologics remain a burden on healthcare systems and patients. Janus kinase inhibitors are small-molecule drugs that can be administered orally and are relatively inexpensive, thus offering an additional option for treating IBD. They have been shown to be effective in patients with ulcerative colitis (UC), but they are less effective in those with Crohn’s disease (CD). Nonetheless, given the immune-system-based mechanism of these drugs, their safety profile remains a cause for concern. This article provides an overview of Janus kinase (JAK) inhibitors and new trends in the treatment of IBD.

scholarly journals Treatment of inflammatory bowel diseases: focusing on biologic agents and new therapies

2021 ◽  
Vol 64 (9) ◽  
pp. 605-613
Author(s):  
Hyo Yeop Song ◽  
Geom Seog Seo
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Biologic Agents ◽  
Janus Kinase ◽  
Interleukin 12 ◽  
New Therapies ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background: The treatment of inflammatory bowel diseases has evolved with the development of anti-tumor necrosis factor agents. Despite the long-term effectiveness, many patients experience primary non-response, secondary loss of response, or intolerance. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. This review focuses on biologic agents and new therapies for the treatment of inflammatory bowel diseases.Current Concepts: Vedolizumab, a gut-selective agent that targets α4β7 integrin is effective in both ulcerative colitis and Crohn’s disease. Ustekinumab is a monoclonal antibody that binds to p40 subunit of interleukin-12/interleukin-23. Ustekinumab is available for the treatment of Crohn’s disease and ulcerative colitis. Tofacitinib is the first Janus kinase inhibitor approved for the treatment of ulcerative colitis. The advantage of tofacitinib is an oral prescription medicine and has rapid action.Discussion and Conclusion: Since vedolizumab, ustekinumab and tofacitinib are effective agents for the treatment of inflammatory bowel diseases, positioning of old and new biologic agents and small molecules should be determined. The safety and efficacy of novel and emerging drugs needs to be evaluated in patients with inflammatory bowel disease.

Emerging Therapies for Inflammatory Bowel Diseases

2016 ◽  
Vol 34 (Suppl. 1) ◽  
pp. 67-73 ◽  
Author(s):  
Reena Khanna ◽  
Brian G. Feagan
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Janus Kinase ◽  
Interleukin 12 ◽  
Cytokine Signaling ◽  
Treatment Algorithms ◽  
Signal Transducers ◽  
Emerging Therapies ◽  
Bowel Diseases ◽  
Risk Patients ◽  
Inflammatory Bowel

Background: The past decade has seen important advances in the management of chronic inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis. The development of TNF antagonists, the recognition of interrupting lymphocyte trafficking as an effective treatment strategy, confirmation of the value of combination therapy, and the need, particularly in CD, for the treatment of high-risk patients early in the disease course are all fundamental concepts upon which the next generation of IBD treatment algorithms will be built. Emerging concepts that will continue to evolve and shape the field include an increased emphasis on personalized medicine (right drug, right dose, right time) and the development of new therapeutic classes. In this article, we review the clinical data and provide some insights into recent data regarding IBD therapies. Key Messages: In this article, we review the mechanism of action and data for novel therapies in IBD with particular focus on the evidence for agents targeting leukocyte trafficking, cytokine signaling, including interleukin-12/23 and the Janus kinase-signal transducers/activators of transcription pathway, and the emergence of antisense therapy for the treatment of IBD. Conclusions: Multiple new therapies are emerging for IBD; however, the potential positioning of these agents in treatment algorithms is difficult to predict in the absence of comparative effectiveness studies.

Anti-adhesion Molecules in IBD: Does Gut Selectivity Really Make the Difference?

2019 ◽  
Vol 25 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Ferdinando D'Amico ◽  
Giulia Roda ◽  
Laurent Peyrin-Biroulet ◽  
Silvio Danese
Keyword(s):  
Adhesion Molecules ◽  
Biological Treatment ◽  
Current Data ◽  
New Drugs ◽  
Inflammatory Infiltration ◽  
New Class ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Difference ◽  
Necrosis Factor

Inflammatory Bowel Disease is lifetime chronic progressive inflammatory disease. A considerable portion of patients, do not respond or lose response or experience side effect to “traditional” biological treatment such as anti-tumor necrosis factor (TNF)-α agents. The concept that the blockade of T cell traffic to the gut controls inflammation has stimulated the development of new drugs which selectively targets molecules involved in controlling cell homing to the intestine. The result is the reduction of the chronic inflammatory infiltration in the gut. In this regard, anti-adhesion molecules represent a new class of drugs for patients who don’t respond or lose response to traditional therapy. Moreover, some of these molecules such as vedolizumab, offer the advantage to target the delivery of a drug to the gut (gut selectivity) which could increase clinical efficacy and limit potential adverse events. In this article, we will give an overview of the current data on anti-adhesion molecules in Inflammatory Bowel Diseases.

scholarly journals Clinical Pharmacology of Janus Kinase Inhibitors in Inflammatory Bowel Disease

2020 ◽  
Vol 14 (Supplement_2) ◽  
pp. S725-S736 ◽  
Author(s):  
Pavine L C Lefevre ◽  
Niels Vande Casteele
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Pharmacology ◽  
Gastrointestinal Tract ◽  
Bowel Disease ◽  
Kinase Inhibitors ◽  
Response To Therapy ◽  
Janus Kinase ◽  
Janus Kinase Inhibitors ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, are chronic inflammatory disorders of the gastrointestinal tract which are characterised, in part, by an imbalance in the production of several pro- and anti-inflammatory cytokines. Although various agents are effective for inducing and maintaining remission, approximately 20% of patients are treatment-refractory and require surgery. Parenterally administered monoclonal antibody-based biologics are associated with adverse effects resulting in treatment discontinuation and/or immunogenicity, leading to loss of response to therapy. Approximately 50% of patients who initially respond to treatment with tumour necrosis factor antagonists lose response to therapy within the 1st year of treatment. Incidence of immunogenicity tends to decrease over time, but once present can persist for years, even after treatment discontinuation. Nonimmunogenic oral small molecule therapies, including Janus kinase inhibitors, are currently being developed and have demonstrated efficacy in early phase clinical trials, which has already led to regulatory approval of tofacitinib for the treatment of patients with moderate-to-severe ulcerative colitis. Differentiation of T cells into T helper cells, which are mediators of the inflammatory response in inflammatory bowel disease, is mediated by the Janus kinase signal transducer and activator of the transcription signalling pathway. Absorption and distribution of Janus kinase inhibitors occurs at the site of action in the gastrointestinal tract, and newer compounds are being developed with limited systemic absorption, potentially reducing the risk of adverse effects. The current review describes the clinical pharmacology of approved Janus kinase inhibitors, as well as those in clinical development for the treatment of inflammatory bowel disease.

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