Systematic review with meta-analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease

2019 ◽  
Vol 50 (1) ◽  
pp. 5-23 ◽  
Author(s):  
Christopher Ma ◽  
Jeffrey K. Lee ◽  
Anish R. Mitra ◽  
Anouar Teriaky ◽  
Daksh Choudhary ◽  
...  
Keyword(s):  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Efficacy And Safety ◽  
Janus Kinase Inhibitors ◽  
Inflammatory Bowel

JAK Inhibition as a Therapeutic Strategy for Inflammatory Bowel Disease

2020 ◽  
Vol 21 (4) ◽  
pp. 247-255 ◽  
Author(s):  
Fabio Salvatore Macaluso ◽  
Iago Rodríguez-Lago
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Mechanism Of Action ◽  
Bowel Disease ◽  
Therapeutic Strategy ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Efficacy And Safety ◽  
Janus Kinase Inhibitors ◽  
Inflammatory Bowel

Background: Inflammatory bowel disease, including both Crohn’s disease and ulcerative colitis, are two chronic and progressive disorders affecting the gastrointestinal tract. Research on the molecular mechanisms of both diseases has led to the introduction of targeted therapies which are able to selectively block the key inflammatory mediators. Methods: Here, we discuss the current evidence about the mechanism of action with an up to date review of the efficacy and safety of Janus kinase inhibitors in inflammatory bowel disease. Results: Multiple small molecule drugs have been evaluated for their use in both ulcerative colitis and Crohn’s disease. Janus kinase inhibitors represent the most important family of these drugs, as their particular mechanism of action enables a simultaneous and effective blockade of multiple cytokines involved in the pathogenesis of the disease. Conclusion: Janus kinase inhibitors represent a promising therapeutic strategy, especially in ulcerative colitis. More data are still necessary regarding its efficacy and safety in clinical practice.

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.

Advances in the Development of Janus Kinase Inhibitors in Inflammatory Bowel Disease: Future Prospects

Drugs ◽  
2017 ◽  
Vol 77 (10) ◽  
pp. 1057-1068 ◽  
Author(s):  
Mathurin Flamant ◽  
Josselin Rigaill ◽  
Stephane Paul ◽  
Xavier Roblin
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Future Prospects ◽  
Janus Kinase Inhibitors ◽  
Inflammatory Bowel

scholarly journals The Future of Janus Kinase Inhibitors in Inflammatory Bowel Disease

2017 ◽  
Vol 11 (7) ◽  
pp. 885-893 ◽  
Author(s):  
L.C.S. De Vries ◽  
M.E. Wildenberg ◽  
W.J. De Jonge ◽  
G.R. D’Haens
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Janus Kinase Inhibitors ◽  
The Future ◽  
Inflammatory Bowel

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.

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