Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis

Rheumatology 2013;52:1556–1562 doi:10.1093/rheumatology/ket225

Both the innate and adaptive immune responses are targeted by current RA treatments, but these treatments do not achieve consistent sustained disease remission. Protein kinase inhibitors represent a promising new therapeutic target, owing to their influence on downstream signalling and oral bioavailability. Fostamatinib (R788) has shown ACR20 responses of 67–72% in MTX inadequate responder patients at doses of 100mg bd and 150mg bd. However, the results in biologic non-responder patients were no...

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June 2013

This review describes cytokines and the cytokine network in chronic inflammatory diseases such as rheumatoid arthritis (RA). It also discusses how therapies that target cytokines may be feasible and efficacious treatments option for RA. Various targets are considered including blockade of tumour necrosis factor (TNF) and interleukin-1 (IL-1), as well as the targeting of cytokines that play a central role in immune regulation and tissue matrix destruction such as IL-6, IL-15, interferon-gamma (IF...

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Cytokines in the pathogenesis of rheumatoid arthritis

Nature Reviews Immunology 2007; 7:429-42

The imbalance between the activity of pro- and anti-inflammatory cytokines favouring induction of autoimmunity, chronic inflammation and joint damage is well known, but how cytokines are organised within a hierarchical regulatory network and which cytokines are the best targets for clinical intervention is uncertain. This review therefore examines the effector function of cytokines in the immunological processes central to the pathogenesis of rheumatoid arthritis (RA). The paper aims to try and ...

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...
This review paper considers how advances in understanding of the disease process underlying rheumatoid arthritis (RA) and the development of novel techniques have transformed the management of this progressively disabling condition. Physicians are no longer limited to prescribing symptomatic treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) or choosing from a seemingly random array of drugs drawn from multiple disciplines, such as methotrexate and sulphasalazine, which are descri...

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This randomised, placebo-controlled, multicentre phase 2 study evaluated the efficacy and safety of atorvastatin versus placebo in modifying lipids in 111 patients with active rheumatoid arthritis (RA) receiving tofacitinib. All patients took tofacitinib 10 mg twice daily for 12 weeks, and after the first 6 weeks patients were randomised 1:1 to receive either atorvastatin 10 mg once daily (n=50) or matched placebo (n=48) in a double-blind phase for a further 6 weeks. Tofacitinib-induced elevatio...