Literature DB >> 27177233

Tofacitinib for the treatment of ulcerative colitis.

Roberta Izzo1, Gerolamo Bevivino1, Giovanni Monteleone1.   

Abstract

INTRODUCTION: Management of patients with active ulcerative colitis (UC), one of the most frequent inflammatory bowel diseases in human beings, is mainly based on the use of mesalamine and corticosteroids. Since in the long-term, these two drugs may be ineffective in nearly one third of the patients, immunosuppressants and/or biologics are needed to control disease activity. AREAS COVERED: The marked activation of JAK/STAT molecules in inflamed mucosa of UC patients and the demonstration that UC-associated mucosal injury is driven by soluble factors that signal through JAK/STAT pathways led to investigation of JAK inhibitors for the treatment of active UC. Tofacitinib, an oral inhibitor of the cytokine-driven JAK-STAT signalling cascade, has recently been proposed for the treatment of moderate-to-severe UC. Phase 2 study showed the efficacy of tofacitinib to induce clinical and endoscopic improvement/remission and the safety profile of the drug. Herein the authors review this compound. EXPERT OPINION: The results obtained from clinical trials with tofacitinib suggest that this drug could be a new treatment option for patients with moderate to severe UC. However, further experimentation is needed to assess the efficacy of this drug in selected subgroups of patients as well as to maintain remission and to determine the long-term safety profile of the drug.

Entities:  

Keywords:  CD4+ T cells; JAK; STAT; cytokines; inflammatory bowel diseases; intestinal inflammation

Mesh:

Substances:

Year:  2016        PMID: 27177233     DOI: 10.1080/13543784.2016.1189900

Source DB:  PubMed          Journal:  Expert Opin Investig Drugs        ISSN: 1354-3784            Impact factor:   6.206


  7 in total

1.  Tofacitinib inhibits inflammatory cytokines from ulcerative colitis and healthy mucosal explants and is associated with pSTAT1/3 reduction in T-cells.

Authors:  Rhonda M Brand; Beverley A Moore; Ashley Zyhowski; Aaron Siegel; Shikhar Uttam; E Jeffrey Metter; Jarret Engstrom; Randall E Brand; Nabanita Biswas; David C Whitcomb; David G Binion; Marc Schwartz; Ian McGowan
Journal:  Am J Physiol Gastrointest Liver Physiol       Date:  2020-12-23       Impact factor: 4.052

2.  Tofacitinib for induction of remission in ulcerative colitis: systematic review and meta-analysis.

Authors:  Paschalis Paschos; Anastasia Katsoula; Olga Giouleme; Maria Sarigianni; Aris Liakos; Eleni Athanasiadou; Eleni Bekiari; Apostolos Tsapas
Journal:  Ann Gastroenterol       Date:  2018-05-10

Review 3.  Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders.

Authors:  Patrizia Fasching; Martin Stradner; Winfried Graninger; Christian Dejaco; Johannes Fessler
Journal:  Molecules       Date:  2017-01-14       Impact factor: 4.411

4.  Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib.

Authors:  Kevin L Winthrop; Gil Y Melmed; Séverine Vermeire; Millie D Long; Gary Chan; Ronald D Pedersen; Nervin Lawendy; Andrew J Thorpe; Chudy I Nduaka; Chinyu Su
Journal:  Inflamm Bowel Dis       Date:  2018-09-15       Impact factor: 5.325

5.  Topical Administration of 0.3% Tofacitinib Suppresses M1 Macrophage Polarization and Allograft Corneal Rejection by Blocking STAT1 Activation in the Rat Cornea.

Authors:  Jianfeng Yu; Pengfei Li; Zhuang Li; Yingqi Li; Jiawei Luo; Wenru Su; Dan Liang
Journal:  Transl Vis Sci Technol       Date:  2022-03-02       Impact factor: 3.048

6.  Targeting Lineage-Specific Transcription Factors and Cytokines of the Th17/Treg Axis by Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Attenuates TNBS-Induced Experimental Colitis.

Authors:  Marta Szandruk-Bender; Benita Wiatrak; Stanisław Dzimira; Anna Merwid-Ląd; Łukasz Szczukowski; Piotr Świątek; Adam Szeląg
Journal:  Int J Mol Sci       Date:  2022-08-31       Impact factor: 6.208

Review 7.  Efficacy of JAK inhibitors in Crohn's Disease.

Authors:  Gerhard Rogler
Journal:  J Crohns Colitis       Date:  2020-08-01       Impact factor: 9.071

  7 in total

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