JAK selectivity for inflammatory bowel disease treatment: does it clinically matter?

Abstract:

:The two major forms of inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated conditions characterised by an increased production of pro-inflammatory cytokines that act as critical drivers of intestinal inflammation. Anti-cytokine therapy has been shown to improve clinical outcomes in IBD. Janus kinases (JAKs) are tyrosine kinases that bind different intracellular cytokine receptors, leading to phosphorylation of signal transducer and activation of transcription molecules implicated on targeted gene transcription. Four isoforms of JAKs have been described: JAK1, JAK2, JAK3 and TYK2. Oral JAK inhibitors (JAKi) have been developed as synergic anti-cytokine therapy in IBD, showing different selectivity towards JAK isoforms. Tofacitinib, a pan-JAK inhibitor, has been recently approved for the treatment of moderate-to-severe UC. With the aim of improving the benefit: risk ratio of this drug class, several second-generation subtype-selective JAKi are under development. However, whether selective inhibition of JAK isoforms is associated with an increased clinical efficacy and/or a better safety profile remains debatable. The aim of this review is to critically review the preclinical and clinical data for the differential selectivity of JAK inhibitors and to summarise the potential clinical implications of the selective JAK inhibitors under development for UC and CD.

journal_name

Gut

journal_title

Gut

authors

Danese S,Argollo M,Le Berre C,Peyrin-Biroulet L

doi

10.1136/gutjnl-2019-318448

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1893-1899

issue

10

eissn

0017-5749

issn

1468-3288

pii

gutjnl-2019-318448

journal_volume

68

pub_type

杂志文章,评审

相关文献

GUT文献大全
  • Plasma insulin, serum lipids and lipoproteins in gall stone disease in non-insulin dependent diabetic subjects: a case control study.

    abstract::Fasting insulin, lipids and lipoproteins were measured in 22 middle aged female non-insulin dependent diabetics with gall stone disease (cases) and in 22 non-insulin dependent diabetics without gall stone disease (controls). The groups were matched for sex, age, obesity, and fasting glucose concentrations. No differen...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.31.3.344

    authors: Laakso M,Suhonen M,Julkunen R,Pyörälä K

    更新日期:1990-03-01 00:00:00

  • Intestinal metaplasia at the gastro-oesophageal junction: Helicobacter pylori gastritis or gastro-oesophageal reflux disease?

    abstract:BACKGROUND:Intestinal metaplasia, whether in the cardia or the distal oesophagus, has been uniformly defined as specialised columnar epithelium, suggesting a relation with Barrett's oesophagus. It is, however, not clear whether the risk factors associated with intestinal metaplasia are identical at both sites. AIMS:To...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.43.1.17

    authors: Hackelsberger A,Günther T,Schultze V,Manes G,Dominguez-Muñoz JE,Roessner A,Malfertheiner P

    更新日期:1998-07-01 00:00:00

  • Role of intracellular Ca2+ and the calmodulin messenger system in pepsinogen secretion from isolated rabbit gastric mucosa.

    abstract::Both carbachol (10(-4)-10(-3) mol/l) and cholecystokinin octapeptide (CCK-8) (10(-8)-10(-6) mol/l) significantly stimulated the release of pepsinogen from rabbit gastric mucosa maintained in organ culture (213-216% and 143-261% of control, respectively, p less than 0.05-0.01). The secretion was not affected by removin...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.33.1.21

    authors: Miyamoto T,Itoh M,Noguchi Y,Yokochi K

    更新日期:1992-01-01 00:00:00

  • Rebamipide, a novel antiulcer agent, attenuates Helicobacter pylori induced gastric mucosal cell injury associated with neutrophil derived oxidants.

    abstract::The effect of rebamipide, a novel antiulcer compound, on Helicobacter pylori activated neutrophil dependent in vitro gastric epithelial cell injury was investigated. Luminol dependent chemiluminescence (ChL), which detects toxic oxidants from neutrophils exhibited a 12-fold increase when the bacterial suspension of H ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.35.10.1375

    authors: Suzuki M,Miura S,Mori M,Kai A,Suzuki H,Fukumura D,Suematsu M,Tsuchiya M

    更新日期:1994-10-01 00:00:00

  • Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses.

    abstract:OBJECTIVES:To characterise the association between type 2 diabetes mellitus (T2DM) subtypes (new-onset T2DM (NODM) or long-standing T2DM (LSDM)) and pancreatic cancer (PC) risk, to explore the direction of causation through Mendelian randomisation (MR) analysis and to assess the mediation role of body mass index (BMI)....

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gutjnl-2019-319990

    authors: Molina-Montes E,Coscia C,Gómez-Rubio P,Fernández A,Boenink R,Rava M,Márquez M,Molero X,Löhr M,Sharp L,Michalski CW,Farré A,Perea J,O'Rorke M,Greenhalf W,Iglesias M,Tardón A,Gress TM,Barberá VM,Crnogorac-Jurcevic T,

    更新日期:2021-02-01 00:00:00

  • Inability of normal human intestinal macrophages to form multinucleated giant cells in response to cytokines.

    abstract::Multinucleated giant cells are an important feature of the granulomatous reaction in Crohn's disease (CD) but their cellular origin is poorly understood. The aim of this study was to discover if intestinal macrophages are capable of generating multinucleated giant cells in vitro in response to cytokine stimulation. Hu...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.37.6.798

    authors: Fais S,Pallone F

    更新日期:1995-12-01 00:00:00

  • Effect of secretogogues on mucosal blood flow in the antrum and corpus of the stomach.

    abstract::Gastric mucosal blood flow in the rat was determined by the indicator fractionation technique of Sapirstein using Rb86Cl. Antral and corpus flow rates were determined in response to increasing doses of pentagastrin and histamine and the effect of vagotomy was determined. With progressive stimulation the antral:corpus ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.19.1.14

    authors: Taylor TV,Pullan BR,Goddard J,Torrance B

    更新日期:1978-01-01 00:00:00

  • INK4a-ARF alterations in liver cell adenoma.

    abstract:BACKGROUND:The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16(INK4a) and p14(ARF), whose functions are inactivated in many human cancers. AIMS:To evaluate p14(ARF) and p16(INK4a) alterations in liver cell adenoma. METHODS:After microdissection, DNA from 25 liver cell adenomas ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.51.2.253

    authors: Tannapfel A,Busse C,Geissler F,Witzigmann H,Hauss J,Wittekind C

    更新日期:2002-08-01 00:00:00

  • Reticuloendothelial function in coeliac disease and ulcerative colitis.

    abstract::Patients with ulcerative colitis and coeliac disease who had been shown by impaired clearance of heat damaged red cells to have diminished splenic phagocytosis, were examined for evidence of more generalised reticuloendothelial malfunction by measuring their circulatory clearance of micro-aggregated albumin. Although ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.24.5.384

    authors: Palmer KR,Barber DC,Sherriff SB,Holdsworth CD

    更新日期:1983-05-01 00:00:00

  • Pk11195, a mitochondrial benzodiazepine receptor antagonist, reduces apoptosis threshold in Bcl-X(L) and Mcl-1 expressing human cholangiocarcinoma cells.

    abstract:BACKGROUND:Cholangiocarcinoma cells express high levels of the antiapoptotic proteins Bcl-X(L) and Mcl-1 and are markedly chemo- and radioresistant. Mitochondria have emerged as central players in apoptosis. Antiapoptotic members of the Bcl-2 protein family localise to the outer mitochondrial membrane and regulate mito...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.51.4.556

    authors: Okaro AC,Fennell DA,Corbo M,Davidson BR,Cotter FE

    更新日期:2002-10-01 00:00:00

  • Chemoprevention of colorectal cancer.

    abstract::Colorectal cancer is the fourth commonest form of cancer in men with 678 000 estimated new cases per year worldwide, representing 8.9% of all new cancers. The disease is most frequent in Occidental countries and particularly so in North America, Australia, New Zealand, and parts of Europe. Prospects for colorectal can...

    journal_title:Gut

    pub_type: 杂志文章,评审

    doi:10.1136/gut.43.4.578

    authors: Langman M,Boyle P

    更新日期:1998-10-01 00:00:00

  • An ultrastructural study of the liver in Indian childhood cirrhosis with particular reference to the structure of cytoplasmic hyaline.

    abstract::Ultrastructural features of the liver in eight cases of Indian childhood cirrhosis, a fatal and elusive liver disease in India, have been described. Severe parenchymal damage, diffuse creeping fibrosis, and other light microscopic alterations, including the frequent presence of cytoplasmic hyaline, reported earlier ar...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.12.9.693

    authors: Roy S,Ramalingaswami V,Nayak NC

    更新日期:1971-09-01 00:00:00

  • Simplified cholangiography using ioglycamide.

    abstract::Intravenous cholangiograms were performed on 100 unselected nonicteric patients using methylglucamine ioglycamide (Biligram). Fifty patients received 10.5 g of contrast medium and 50 received 5.25 g of medium. The contrast medium was injected evenly over five minutes. Side effects were recorded in only 13% of patients...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.15.4.268

    authors: Parkin GJ,Herlinger H

    更新日期:1974-04-01 00:00:00

  • Bowel diversion should be used with caution in stenosing anal Crohn's disease.

    abstract::Proximal diversion has commonly been used for severe perianal Crohn's disease in an attempt to relieve local symptoms, whether the primary intestinal disease is in the colon or small bowel. Two patients are presented in whom diversion led to severe symptomatic disease in the previously normal defunctioned bowel. In ea...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.35.8.1139

    authors: Williamson ME,Hughes LE

    更新日期:1994-08-01 00:00:00

  • Abdominal decompression plays a major role in early postparacentesis haemodynamic changes in cirrhotic patients with tense ascites.

    abstract:BACKGROUND:Some cirrhotic patients with tense ascites who undergo paracentesis develop a circulatory dysfunction syndrome, manifested by an increase in plasma renin activity. Recently, a significant inverse correlation between postparacentesis changes in plasma renin activity and systemic vascular resistance has been d...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.48.3.384

    authors: Cabrera J,Falcón L,Gorriz E,Pardo MD,Granados R,Quinones A,Maynar M

    更新日期:2001-03-01 00:00:00

  • Radiographic evaluation of pancreatico-jejunal shunts.

    abstract::This paper describes opacification and identification of two surgically constructed pancreatico-jujunal shunts. A fibreoptic panendoscope was used with retrograde injection via the ampulla of Vater (ERCP). This procedure makes possible more accurate anatomical evaluation and so more precise clinical appraisal of both...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.17.6.439

    authors: Miller EW,Goldberg HI,Goldberg SB,Shapiro H

    更新日期:1976-06-01 00:00:00

  • The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis.

    abstract:OBJECTIVE:To clarify the prognostic role of tumour protein 53 (TP53) mutations in patients with oesophageal adenocarcinoma (OAC) as there is a need for biomarkers that assist in guiding management for patients with OAC. DESIGN:A systematic review was conducted using MEDLINE, Embase, PubMed and Current Contents Connect...

    journal_title:Gut

    pub_type: 杂志文章,meta分析,评审

    doi:10.1136/gutjnl-2015-310888

    authors: Fisher OM,Lord SJ,Falkenback D,Clemons NJ,Eslick GD,Lord RV

    更新日期:2017-03-01 00:00:00

  • Serum hepatocyte growth factor as an index of extensive catabolism of patients awaiting liver transplantation.

    abstract:BACKGROUND:Whole body catabolism as the result of intrahepatic metabolic derangement is common in liver transplant candidates. However, individual nutritional assessment parameters lack sensitivity and specificity in determining energy status of these patients. Recently, serum hepatocyte growth factor (HGF) has been sh...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.44.6.862

    authors: Miki C,Mayer AD,Buckels JA,Iriyama K,Suzuki H,McMaster P

    更新日期:1999-06-01 00:00:00

  • Glucosamine synthetase activity of the colonic mucosa in membranous colitis.

    abstract::Glucosamine synthetase, the first enzyme in glycoprotein synthesis, has been measured in serial rectal biopsies in four patients with membranous colitis. In two of the patients the levels of the enzyme were very high initially and in the other two patients the enzyme levels rose to a peak above the normal range after ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.18.3.229

    authors: Goodman MJ,Kent PW,Truelove SC

    更新日期:1977-03-01 00:00:00

  • Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence.

    abstract:OBJECTIVE:In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 (CARD9), a key innate immunity gene, is required to shape a normal gut microbiota. Card9-/- mice are more susceptible to the enteric mouse pathogen C...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gutjnl-2017-314195

    authors: Lamas B,Michel ML,Waldschmitt N,Pham HP,Zacharioudaki V,Dupraz L,Delacre M,Natividad JM,Costa GD,Planchais J,Sovran B,Bridonneau C,Six A,Langella P,Richard ML,Chamaillard M,Sokol H

    更新日期:2018-10-01 00:00:00

  • Lipid peroxidation in rats chronically fed ethanol.

    abstract::Chronic alcohol consumption induces cytochrome P450IIE1, enabling habitual abusers to consume far greater quantities of alcohol than normal subjects. This pathway of metabolism leads to the production of free radical species, which cause tissue damage through peroxidation of cell membranes. Groups of Wistar rats of eq...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.35.11.1644

    authors: Teare JP,Greenfield SM,Watson D,Punchard NA,Miller N,Rice-Evans CA,Thompson RP

    更新日期:1994-11-01 00:00:00

  • Gall bladder emptying in severe idiopathic constipation.

    abstract:BACKGROUND:It has been suggested that slow transit constipation (STC) may be part of a panenteric motor disorder. AIM:To evaluate motility of an upper gastrointestinal organ, the gall bladder, in 16 patients with STC and 20 healthy controls. METHODS:Gall bladder emptying (ultrasonography) was studied in response to n...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.45.2.264

    authors: Penning C,Gielkens HA,Delemarre JB,Lamers CB,Masclee AA

    更新日期:1999-08-01 00:00:00

  • Evaluation of the trophic effect of longterm treatment with the histamine H2 receptor antagonist loxtidine on rat oxyntic mucosa by differential counting of dispersed cells.

    abstract::To evaluate whether the general trophic effect of gastrin on the oxyntic mucosa is an indirect effect mediated by histamine H2 receptors, sustained 24 hour hypergastrinaemia was induced in Sprague-Dawley rats by treatment with the long acting and potent histamine H2 antagonist loxtidine for five months. The trophic ef...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.35.11.1547

    authors: Brenna E,Swarts HG,Klaassen CH,de Pont JJ,Waldum HL

    更新日期:1994-11-01 00:00:00

  • Short chain fatty acids in human large intestine, portal, hepatic and venous blood.

    abstract::Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within fou...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.28.10.1221

    authors: Cummings JH,Pomare EW,Branch WJ,Naylor CP,Macfarlane GT

    更新日期:1987-10-01 00:00:00

  • Laparoscopic biliary and gastric bypass: a useful adjunct in the treatment of carcinoma of the pancreas.

    abstract::Over 90% of patients with inoperable carcinoma of the pancreas are successfully palliated by endoscopic retrograde cholangiopancreatography and stent insertion. Treatment of the residual 10% of patients often entails a laparotomy, which is difficult to justify when median survival of these patients is only 150 days. L...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.36.5.778

    authors: Rhodes M,Nathanson L,Fielding G

    更新日期:1995-05-01 00:00:00

  • Evaluation of colonic myoelectrical activity in health and functional disorders.

    abstract::Electrical activity of the colon was investigated in six healthy volunteers and 22 patients presenting functional colonic disorders associated with pain, constipation, or diarrhoea. Myoelectrical activity during 10 hours, including two daily meals, was recorded from eight groups of nickel-chrome electrodes using a 1.5...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.21.6.480

    authors: Bueno L,Fioramonti J,Ruckebusch Y,Frexinos J,Coulom P

    更新日期:1980-06-01 00:00:00

  • Mislocalisation of hephaestin, a multicopper ferroxidase involved in basolateral intestinal iron transport, in the sex linked anaemia mouse.

    abstract:BACKGROUND:Hephaestin is a multicopper ferroxidase required for basolateral transport of iron from enterocytes. Sex linked anaemia (sla) mice have a defect in the release of iron from intestinal enterocytes into the circulation due to an interstitial deletion in the hephaestin gene (heph). RESULTS:We have demonstrated...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.2003.019026

    authors: Kuo YM,Su T,Chen H,Attieh Z,Syed BA,McKie AT,Anderson GJ,Gitschier J,Vulpe CD

    更新日期:2004-02-01 00:00:00

  • Effect of scheduled second therapeutic endoscopy on peptic ulcer rebleeding: a prospective randomised trial.

    abstract:AIM:Recurrent bleeding after initial haemostasis is an important factor that directly relates to the outcome in the management of peptic ulcer bleeding. Conflicting reports have been published concerning the effectiveness of scheduled second therapeutic endoscopy on ulcer rebleeding. We investigate the use of scheduled...

    journal_title:Gut

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1136/gut.52.10.1403

    authors: Chiu PW,Lam CY,Lee SW,Kwong KH,Lam SH,Lee DT,Kwok SP

    更新日期:2003-10-01 00:00:00

  • Abnormalities of B-cell activation and immunoregulation in patients with Crohn's disease.

    abstract::We have studied B-lymphocyte function in 39 patients with Crohn's disease and 35 normal individuals using a reverse haemolytic plaque assay as the effector system. Ten patients had active Crohn's disease, the others being in an inactive state of the disease. Compared with normal individuals, the Crohn's disease patien...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.25.11.1255

    authors: Sieber G,Herrmann F,Zeitz M,Teichmann H,Rühl H

    更新日期:1984-11-01 00:00:00

  • Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer.

    abstract:BACKGROUND:Helicobacter pylori affects gastric epithelium integrity by acceleration of apoptosis. However, it remains unclear what product of the bacteria causes apoptosis, or whether or not the apoptosis is involved in the development of ulcers. AIMS:To elucidate the factor from H pylori that causes acceleration of a...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.44.4.456

    authors: Kohda K,Tanaka K,Aiba Y,Yasuda M,Miwa T,Koga Y

    更新日期:1999-04-01 00:00:00