June 2013

The pathogenesis of rheumatoid arthritis

The New England Journal of Medicine 2011; 365:2205-19

This review article describes the pathogenic processes involved in rheumatoid arthritis (RA) and discusses the genetic factors and environmental triggers implicated in the disease. Data from twin studies are discussed along with candidate genes with single nucleotide polymorphisms (SNPs) that have been linked to RA. It is now thought a multistep progression to the development of RA occurs via environmental factors, epigenetic modification of susceptible genes that leads to altered post-transcrip...

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Janus kinases inhibitors in autoimmune diseases

Annals of the Rheumatic Diseases 2013; 72:ii111-ii115

This review describes the role of various cytokines in rheumatoid arthritis (RA) and related diseases. This includes an overview of the different types of cytokine receptors including type I, which bind some of the interleukins (ILs), colony stimulating factors (CSFs) and hormones such as erythropoietin, prolactin and growth hormone (GH); and type II, which bind to interferons and IL-10-related proteins. In addition, the cytoplasmic domain of type I and II cytokine receptors bind to members of a...

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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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The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: autocrine role of type 1 interferon

Annals of Rheumatic Diseases 2012; 71:440-47

This study investigated the effect of the novel Janus kinase (JAK) inhibitor CP-690,550 [tofacitinib] in fibroblast-like synoviocytes (FLSs) collected from patients with rheumatoid arthritis (RA). Human FLSs were cultured from the synovial tissue of patients with RA who were undergoing arthroplastic surgery, cultured and then serum-starved 48 hours prior to stimulation. Quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) or multiplex bead assay were used to...

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Effects of fostamatinib (R788), an oral spleen tyrosine kinase inhibitor, on health-related quality of life in patients with active rheumatoid arthritis: analyses of patient-reported outcomes from a randomized, double-blind, placebo-controlled trial

The Journal of Rheumatology 2013; 40(3):369-78

This phase 2 clinical trial assessed the influence of fostamatinib on patient reported outcomes (PROs) in 457 patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Patients received either placebo or fostamatinib 100 mg twice daily or 150 mg once daily (1:1:1) for 24 weeks in addition to their baseline MTX. Patients taking fostamatinib 100 mg twice daily had statistically significant improvements in health-related quality of life scores for pain, patien...

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