Document Detail


JAK inhibitor tofacitinib for treating rheumatoid arthritis: from basic to clinical.
MedLine Citation:
PMID:  23212593     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Rheumatoid arthritis (RA) is a representative autoimmune disease characterized by chronic and destructive inflammatory synovitis. The multiple cytokines play pivotal roles in RA pathogenesis by inducing intracellular signaling, and members of the Janus kinase (JAK) family are essential for such signal transduction. An orally available JAK3 inhibitor, tofacitinib, has been applied for RA, with satisfactory effects and acceptable safety in multiple clinical examinations. From phase 2 dose-finding studies, tofacitinib 5 mg and 10 mg twice a day appear suitable for further evaluation. Subsequently, multiple phase 3 studies were carried out, and tofacitinib with or without methotrexate (MTX) is efficacious and has a manageable safety profile in active RA patients who are MTX naïve or show inadequate response to methotrexate (MTX-IR), disease-modifying antirheumatic drugs (DMARD)-IR, or tumor necrosis factor (TNF)-inhibitor-IR. The common adverse events were infections, such as nasopharyngitis; increases in cholesterol, transaminase, and creatinine; and decreases in neutrophil counts. Although the mode of action of tofacitinib remains unclear, we clarified that the inhibitory effects of tofacitinib could be mediated through suppression of interleukin (IL)-17 and interferon (IFN)-γ production and proliferation of CD4(+) T cells in the inflamed synovium. Taken together, an orally available kinase inhibitor tofacitinib targeting JAK-mediated signals would be expected to be a new option for RA treatment.
Authors:
Yoshiya Tanaka; Kunihiro Yamaoka
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-5
Journal Detail:
Title:  Modern rheumatology / the Japan Rheumatism Association     Volume:  -     ISSN:  1439-7609     ISO Abbreviation:  Mod Rheumatol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100959226     Medline TA:  Mod Rheumatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Kitakyushu, 807-8555, Japan, tanaka@med.uoeh-u.ac.jp.
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