October 2015

Phase 3 studies comparing brodalumab with ustekinumab in psoriasis

N Engl J Med 2015;373:1318–28. doi: 10.1056/NEJMoa1503824

Brodalumab treatment resulted in a rapid reduction in the signs and symptoms of PsO. The median time to a PASI 75 response with 210 mg of brodalumab Q2W was 4 weeks, approximately twice as fast as the median time to a response with ustekinumab.

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May 2015

Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial

Arthritis Res Ther. 2015 Apr 6;17(1):95.

Mean increases from baseline in patient serum creatinine (SCr) levels have been observed in the clinical development programme for the JAK inhibitor tofacitinib. These increases predominantly occurred within the first three months, and reversed with tofacitinib withdrawal.

This phase 1, randomised, placebo-controlled, parallel-group, 2-period study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib, relative to placebo, in 148 patients with active RA. Result...

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December 2014

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis

Ann Rheum Dis. 2014 Nov 14. pii: annrheumdis-2014-206028. doi: 10.1136/annrheumdis-2014-206028. [Epub ahead of print]

Targeting intracellular pathways such as JAK/STAT represents a novel approach to the treatment of RA. Tofacitinib is an oral JAK inhibitor, proven to be effective in the treatment of RA, yet the pathways affected by tofacitinib and the effects on gene expression in situ are unknown. In this study, Boyle et al. tested the hypothesis that tofacitinib targets cytokine signalling critical to the pathogenesis of rheumatoid synovitis by investigating tofacitinib effects on synovial pathobiology.

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June 2014

Structural basis for the recognition of interferon-α receptor by tyrosine kinase 2

Nat Struct Mol Biol. 2014 May;21(5):443-8. doi: 10.1038/nsmb.2807. Epub 2014 Apr 6

Janus kinases, JAKs, are essential in the mediation of cytokine and interferon signalling whilst also being crucial to body processes such as immune function, hematopoeises, metabolism and cellular growth. However, it is not known is how the four members of the JAK family interact with and are activated by over 30 cytokine receptors with near perfect affinity and specificity. Currently, there are no crystal structures available for any JAK bound to a cytokine receptor. This study sought address ...

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April 2014

What is the future of targeted therapy in rheumatology: biologics or small molecules?

BMC Medicine 2014, 12:43

Our understanding of inflammatory rheumatic diseases such as rheumatoid arthritis has significantly increased over the last 20 years. With this greater understanding we have seen a significant improvement in the therapy of RA and other inflammatory rheumatic diseases. In this review, Moscai et al. discuss the improvements in therapies for the treatment of these diseases from the introduction of methotrexate as a frontline therapy through to the current era and approval of the first small molecul...

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February 2014

Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis

Ann Rheum Dis doi:10.1136/annrheumdis-2013-204588

Systematic literature reviews were undertaken to assess the efficacy of csDMARDs, glucocorticoids and tofacitinib in the treatment of RA. The first two were updates to reviews conducted for the 2010 recommendations while the tofacitinib SLR was a complete review.Two studies identified by the csDMARD SLR, tREACH and TEAR, compared efficacy between MTX mono- and combination therapy (MTX+SSZ+HQ). Both of these studies found there was no benefit to immediate triple therapy.Further studies analysing ...

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January 2014

STA-21, a promising STAT3 inhibitor that reciprocally regulates Th17 and Treg, inhibits osteoclastgenesis and alleviates autoimmune inflammation

Arthritis and Rheumatism doi: 10.1002/art.38305

STAT3 (signal transducer and activator of transcription 3) is the major transcription factor in the differentiation of Th17 cells, which along with IL-17 are significant in the development of RA. STA-21 is a new small molecule with significant inhibitory effects on STAT3, impeding DNA binding activity, dimerization and STAT3-dependent luciferase activity. While the effect of STA-21 in RA has not been fully determined, it has been hypothesised that STA-21 will suppress arthritis in animal models ...

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November 2013

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update

Ann Rheum Dis. 2013 doi: 10.1136/annrheumdis-2013-204573

The 2010 EULAR recommendations represented a significant step forward in the management of rheumatoid arthritis, and they have been widely adopted across the world. However, in the rapidly evolving world of rheumatology, it was recognised that a substantial amount of new evidence has accumulated, both on agents approved at that time as well as data on new compounds that have become available over the last 3–4 years. This motivated EULAR to form an international task force to update their recomme...

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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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