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Tofacitinib crohn's

J R White, F Phillips, T Monaghan, W Fateen, S Samuel, S Ghosh, G W Moran
BACKGROUND: There is a great unmet clinical need for efficacious, tolerable, economical and orally administrated drugs for the treatment of inflammatory bowel disease (IBD). New therapeutic avenues have become possible including the development of medications that target specific genetic pathways found to be relevant in other immune mediated diseases. AIMS: To provide an overview of recent clinical trials for new generation oral targeted medications that may have a future role in IBD management...
April 19, 2018: Alimentary Pharmacology & Therapeutics
Bram Verstockt, Marc Ferrante, Séverine Vermeire, Gert Van Assche
The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al...
March 19, 2018: Journal of Gastroenterology
Geom Seog Seo, Sung Hee Lee
The treatment of inflammatory bowel disease has evolved with the development of anti-TNF agents. In spite of long-term effectiveness, many patients do not respond or no longer responds to these drugs. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. Vedolizumab, a gut-specific biological agent, inhibits interaction α4β7 integrin with mucosal addressin cell adhesion molecule-1 without inhibiting systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's disease and ulcerative colitis was safe and effective...
February 25, 2018: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
Marcel Vetter, Markus F Neurath
To improve quality of life and prevent long-term risks in patients with inflammatory bowel diseases (IBDs: Crohn's disease, ulcerative colitis), it is essential to suppress inflammatory activity adequately. However, corticosteroids are only suitable for therapy of acute flares and the evidence for positive effects of immunosuppressive substances like azathioprine or 6-mercapropurine is mainly limited to maintenance of remission. In addition, only subgroups of patients benefit from biologicals targeting tumour necrosis factor α or α4β7 integrins...
October 2017: Therapeutic Advances in Gastroenterology
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
February 2018: Annals of the Rheumatic Diseases
Mathurin Flamant, Josselin Rigaill, Stephane Paul, Xavier Roblin
Inflammatory bowel disease (IBD) is caused by a dysregulation of the immune system, inducing the production of proinflammatory cytokines and adhesion molecules. A better understanding of the mucosal immune response in IBD has led to the development of new drugs directed at inflammatory cytokines and leukocyte-trafficking molecules. Beyond tumor necrosis factor antagonists and anti-integrin molecules, which act by blocking the interaction between gut-specific lymphocytes and their receptor on vascular endothelium, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway represents a new target in IBD...
July 2017: Drugs
Julian Panés, William J Sandborn, Stefan Schreiber, Bruce E Sands, Séverine Vermeire, Geert D'Haens, Remo Panaccione, Peter D R Higgins, Jean-Frederic Colombel, Brian G Feagan, Gary Chan, Michele Moscariello, Wenjin Wang, Wojciech Niezychowski, Amy Marren, Paul Healey, Eric Maller
OBJECTIVE: Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). DESIGN: We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks...
June 2017: Gut
J Panés, G R D'Haens, P D R Higgins, L Mele, M Moscariello, G Chan, W Wang, W Niezychowski, C Su, E Maller
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
Sunina Nathoo, William A Hood, Sara Keihanian, Amy L Collinsworth, Sarah C Glover
BACKGROUND: Esophageal Crohn's disease is reported as a rare manifestation, although its prevalence may be underestimated because upper endoscopies are not routinely performed in asymptomatic adults. Tofacitinib, an oral janus kinase inhibitor, is a new biologic that has shown promise in the treatment of ulcerative colitis and may be effective in the treatment of Crohn's disease according to phase 2 trials. We report the first case of esophageal Crohn's disease successfully treated with tofacitinib in a patient with worsening symptoms despite maintenance therapy with a tumor necrosis factor-α inhibitor...
2016: Journal of Medical Case Reports
Robert Roskoski
The Janus kinase (JAK) family of non-receptor protein-tyrosine kinases consists of JAK1, JAK2, JAK3, and TYK2 (tyrosine kinase-2). Each of these proteins contains a JAK homology pseudokinase (JH2) domain that regulates the adjacent protein kinase domain (JH1). JAK1/2 and TYK2 are ubiquitously expressed whereas JAK3 is found predominantly in hematopoietic cells. The Janus kinase family is regulated by numerous cytokines including interleukins, interferons, and hormones such as erythropoietin, thrombopoietin, and growth hormone...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Silvio Danese, Matthew Grisham, Jennifer Hodge, Jean-Baptiste Telliez
The inflammatory diseases ulcerative colitis and Crohn's disease constitute the two main forms of inflammatory bowel disease (IBD). They are characterized by chronic, relapsing inflammation of the gastrointestinal tract, significantly impacting on patient quality of life and often requiring prolonged treatment. Existing therapies for IBD are not effective for all patients, and an unmet need exists for additional therapies to induce and maintain remission. Here we describe the mechanism of action of the Janus kinase (JAK) inhibitor, tofacitinib, for the treatment of IBD and the effect of JAK inhibition on the chronic cycle of inflammation that is characteristic of the disease...
February 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Silvio Danese, Lucine Vuitton, Laurent Peyrin-Biroulet
Six biologic agents are currently approved for the treatment of IBD: four anti-TNF agents (infliximab, adalimumab, golimumab and certolizumab pegol) and two anti-integrin agents (natalizumab and vedolizumab). In Crohn's disease and ulcerative colitis refractory to standard medications, treatment choice among available biologic agents can be challenging. Several parameters should be taken into account to help physicians through the decision-making process, including the comparative effectiveness and long-term safety profile, availability and labelling in the prescriber's country, international guidelines, and cost, as well as patient preferences (such as the route of administration)...
September 2015: Nature Reviews. Gastroenterology & Hepatology
Mark Löwenberg, Geert D'Haens
Various novel drugs have recently been evaluated in clinical trials showing promising effects in patients with inflammatory bowel disease (IBD). Here, we summarize the recent literature in the area of emerging therapies in the field of IBD, with specific focus on anti-integrin antibodies, such as vedolizumab (anti-α4β7) and etrolizumab (anti-rhuMAb β7), and the Janus kinase (JAK) inhibitor tofacitinib. Moreover, we will discuss efficacy and safety data of golimumab (a new subcutaneous anti-tumor necrosis factor (TNF) antibody), Avaxia (an orally delivered anti-TNF antibody), and Budesonide MMX; all have been developed for the treatment of ulcerative colitis...
June 2015: Current Gastroenterology Reports
Juergen Braun, Uta Kiltz, Frank Heldmann, Xenofon Baraliakos
INTRODUCTION: The topic under discussion is of strong relevance to the field of spondyloarthritis (SpA) because, in addition to established biological, there are new promising compounds. The reason for the review is to put all available data together to allow for an overview on recent developments and to especially inform readers about emerging drugs, biologics and small molecules in the field of SpA. AREAS COVERED: This review on new therapies in axial and peripheral SpA comprising psoriatic arthritis (PsA) shows, that, in addition to the established anti-TNF agents infliximab, etanercept, adalimumab, golimumab, certolizumab and the first biosimilar approved in the EU, there are at least two emerging biologics in the field of SpA: ustekinumab, a compound targeting IL12/IL-23 via the p40 subunit of both cytokines works for psoriasis and PsA and probably also for Crohn's disease, and the anti-IL-17 antibody secukinumab which has also been shown to work in psoriasis, both compounds seem to also work in ankylosing spondylitis...
March 2015: Expert Opinion on Emerging Drugs
Bruce E Sands
TNF antagonists have revolutionized the treatment of IBD. Nevertheless, between 30 and 45% of patients discontinue infliximab and other TNF antagonists over a 2- to 6-year period due to nonresponse, loss of response, or adverse events. Accordingly, the need for novel therapies grows each year. Recent studies have demonstrated the promise of new drugs with distinct modes of action for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). These include agents targeting leukocyte trafficking, therapies directed against IL-12/23 and Janus kinases (JAK), and antibodies against the classic inflammatory cytokine, IL-6...
2014: Digestive Diseases
Brigid S Boland, William J Sandborn, John T Chang
Janus kinase (JAK) inhibitors have emerged as a novel orally administered small-molecule therapy for the treatment of ulcerative colitis and possibly Crohn disease. These molecules are designed to selectively target the activity of specific JAKs and to offer a targeted mechanism of action without risk of immunogenicity. Based on data from clinical trials in rheumatoid arthritis and phase 2 studies in inflammatory bowel disease, tofacitinib and other JAK inhibitors are likely to become a new form of medical therapy for the treatment of inflammatory bowel disease...
September 2014: Gastroenterology Clinics of North America
William J Sandborn, Subrata Ghosh, Julian Panes, Ivana Vranic, Wenjin Wang, Wojciech Niezychowski
BACKGROUND & AIMS: Tofacitinib, an orally administered Janus kinase inhibitor, blocks signaling through γ-chain-containing cytokines (interleukins 2, 4, 7, 9, 15, and 21). We performed a phase 2 trial to measure its efficacy in patients with moderate-to-severe active Crohn's disease. METHODS: Patients (N = 139; age, ≥18 y) with moderate-to-severe active Crohn's disease were assigned randomly to groups given 1 mg (n = 36), 5 mg (n = 34), or 15 mg (n = 35) tofacitinib or placebo (n = 34), twice daily for 4 weeks, at 48 centers in 12 countries...
September 2014: Clinical Gastroenterology and Hepatology
Patrick B Allen, Laurent Peyrin-Biroulet
PURPOSE OF REVIEW: The inflammatory bowel diseases (IBDs) are chronic disabling conditions. Despite the benefits of anti-tumor necrosis factor (TNF)-α agents in improving quality of life and reducing the need for surgeries, overall only one-third of patients are in clinical remission at 1 year and loss of response is frequent. It seems clear that treatment must go beyond alleviation of symptoms in IBD. It is important that treatment targets in IBD will ensure mucosal healing and deep remission...
July 2013: Current Opinion in Gastroenterology
Lucine Vuitton, Stéphane Koch, Laurent Peyrin-Biroulet
The advent of anti-Tumor Necrosis Factor (TNF) therapy has changed the way of treating inflammatory bowel disease (IBD). However, primary and secondary failure are relatively frequent with all anti-TNF agents, which are available only as parenteral agents. Tofacitinib is an oral janus kinase (JAK) inhibitor that inhibits JAK family kinase members, in particular JAK1 and JAK3, achieving a broad limitation of inflammation by interfering with several cytokine receptors. It first proved its efficacy as an immunosuppressive regimen after renal transplantation, and was recently approved by the FDA for rheumatoid arthritis...
November 2013: Current Drug Targets
Svend T Rietdijk, Geert R D'Haens
Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases that have been treated with corticosteroids, 5-aminosalicates and thiopurines, but therapeutic options have been broadened with the arrival of anti-tumor necrosis factor antibodies. In this article we reviewed the current evidence-based approach to inflammatory bowel disease, the modifications that have been made to existing therapies and discussed new drugs that have shown success in clinical trials. The new drugs discussed here are those that disturb lymphocyte homing to the gut (natalizumab, vedolizumab and anti-mucosal addressin cellular adhesion molecule); one that blocks interleukin (IL)-12 as well as the IL-23/T helper 17 (Th17) axis (ustekinumab) and one that blocks the signaling of multiple cytokines (tofacitinib)...
June 2013: Journal of Digestive Diseases
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