June 2013

Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes

Best Practice & Research Clinical Rheumatology 2010; 24:513-26

This article reviews data from animal and phase 2 clinical studies assessing the immunomodulatory effects and pharmacokinetics of CP-690,550 (now known as tofacitinib), as well as its efficacy and safety in patients with rheumatoid arthritis (RA). In two rodent models of arthritis, CP-690,550 produced dose-dependent decreases in signs of disease activity compared with untreated controls, reductions in histologically assessed inflammation and articular cartilage damage, and statistically signific...

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Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050

Journal of Immunology 2010; 184(9):5298-307

This preclinical characterisation study examined the efficacy and tolerability of the small molecule INCB028050 (now known as baricitinib), an orally bioavailable, selective Janus kinase (JAK) 1/JAK2 inhibitor, in rodent models of arthritis. The decision to investigate its effects of INCB028050 followed positive evidence for the related compound ruxolitinib, the JAK inhibitor tofacitinib and the IL-6 inhibitor tocilizumab in rheumatoid arthritis (RA). In this preclinical study, INCB028050 was sh...

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Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550)

Journal of Immunology 2011; 186(7):4234-43

This study investigated the effects of the novel Janus kinase (JAK) inhibitor CP-690,550 (now known as tofacitinib) on adaptive and innate immune responses, in order to establish the mode of action of JAK inhibitors in the setting of inflammatory diseases. The inhibition of specific JAK/STAT-dependent pathways by CP-690,550 was determined through analysis of cytokine stimulation of mouse and human T cells in vitro.The effects of CP-690,550 on Th-cell differentiation of naive murine CD4+...

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