JAK inhibitor tofacitinib for treating rheumatoid arthritis: From basic to clinical

Yoshiya Tanaka, Kunihiro Yamaoka

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)415-424
Number of pages10
JournalModern rheumatology
Volume23
Issue number3
DOIs
Publication statusPublished - 2013 May 1

Keywords

  • Inflammation
  • JAK
  • Kinase
  • Rheumatoid arthritis
  • Treatment

ASJC Scopus subject areas

  • Rheumatology

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