February 2018

Professor Iain McInnes Reviews the Most Important Papers from 2017

Please click the links below to go to the CSF review of each paper.

2017 was a successful year for rheumatoid arthritis research, with some key advances in JAK inhibitors and IL-6 inhibitors, as outlined below. - Tofacitinib was suggested as a potential treatment for psoriatic arthritis, and NICE recommended tofacitinib as a treatment for moderate to severe rheumatoid arthritis - Baricitinib studies supported the potential use of baricitinib as a treatment for rheumatoid arthritis - Filgotinib Phase 2 studies suggested that filgotinib could be effective a...

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October 2017

Impact of Tocilizumab Monotherapy On Patient-Reported Outcomes in Patients With Rheumatoid Arthritis from Two Randomised Controlled Trials

RMD Open;3:e000496. doi: 10.1136/rmdopen-2017-000496

This post hoc analysis of 2 randomised controlled trials (RCTs) AMBITION and ADACTA found that tocilizumab monotherapy results in substantial and clinically meaningful improvements in patient-reported outcomes (PROs) over 24 weeks.PROs assessed included patient global assessment (PtGA), pain, HAQ-DI, Functional Assessment of Chronic Illness Therapy (FACIT-F) and Short-Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) and eight domain scores.Tocilizumab (TCZ) mon...

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December 2015

Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis

Ann Rheum Dis. 2015;0:1-7. doi:10.1136/annrheumdis-2015-207872 [Epub ahead of print]

RA patients have increased risk of CVD compared with the general population that is not fully explained by traditional risk factors. This is a post-hoc analysis of data from a clinical trial that compared IL-6 and TNF-α signaling inhibition to compare changes in lipids and lipid-associated CV risk markers in 324 patients treated with TCZ IV q4w or ADA SC q2w for 24 weeks. HDL-SAA and sPLA2 IIA is also measured in an additional subpopulation of 87 and 97 TCZ and ADA patients, respectively.Greater...

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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 2013

An Oral Spleen Tyrosine Kinase (Syk) Inhibitor for Rheumatoid Arthritis

The New England Journal of Medicine 2010; 363(14):1303-12

This is the first phase 2 study to be published for spleen tyrosine kinase (Syk) inhibitor R788 (fostamatinib). This phase 2 study ingestigated the efficacy and safety of fostamatinib in patients with active RA despite long-term treatment with methotrexate. In this 6-month, double-blind, placebo-controlled trial, patients were randomised to receive two doses of R788 (100 mg twice daily or 150 mg once daily) or placebo once or twice daily. Significantly more patients on R788 achieved ACR 20 respo...

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An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents

Arthritis & Rheumatism 2011; 63(2):337-45

This was the first phase 2 study to be published investigating the efficacy and safety of the spleen kinase (Syk) inhibitor R788 (fostamatinib) in patients with refractory rheumatoid arthritis (RA). In this multicentre, randomised, double-blind, placebo-controlled, 3-month trial, patients with active RA on stable background treatment (excluding biologics) were randomised to receive 100 mg R788 or placebo twice daily. Differences in ACR20 responses were significant at week 6 (p=0.003), but not th...

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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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