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Drugs

, Volume 74, Issue 4, pp 415–422 | Cite as

Spleen Tyrosine Kinase Inhibitors for Rheumatoid Arthritis: Where Are We Now?

  • Ian C. Scott
  • David L. Scott
Review Article

Abstract

The development of small-molecule inhibitors of inflammatory cascade signaling kinases offers a potential approach to treating rheumatoid arthritis (RA). Spleen tyrosine kinase is one such tyrosine kinase. Recent research efforts have focussed on the development and testing of a spleen tyrosine kinase inhibitor, fostamatinib. We reviewed the results of the clinical trials of fostamatinib in RA with the aim of outlining its clinical efficacy and the nature and frequency of its main adverse events. To date, this drug has been evaluated in over 3,200 RA patients enrolled in three phase II, one phase IIb and three phase III trials. These studies showed fostamatinib was effective. In four trials in which patients received 100 mg twice daily, fostamatinib reduced inflammatory synovitis; the relative risks of achieving American College of Rheumatology Responder rates compared with placebo in the combined studies ranged from 1.6 for 20 % of responders to 3.7 for 70 % of responders. There was a similar relative risk of achieving a clinically meaningful reduction in disability of 1.6 for the chance of patients achieving a reduction in health assessment questionnaire scores of 0.22 or more. Three of the trials examined the impact of fostamatinib on erosive radiographic damage using changes in the modified total Sharp score. None of them provided any evidence for a significant effect of fostamatinib on erosive damage over 6 months. All the trials included descriptions of adverse events. Hypertension was common, involving over 40 % of patients treated. Other common adverse events included diarrhoea, neutropenia and increases in hepatic enzyme levels. Some patients developed infections. On the conclusion of the phase III trials, one of the main pharmaceutical sponsors decided not to further develop fostamatinib for RA.

Keywords

Rheumatoid Arthritis Adalimumab Minimal Clinically Important Difference Tumour Necrosis Factor Inhibitor Health Assessment Questionnaire 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments and conflict of interest

ICS receives funding from Arthritis Research UK (Grant Reference Number 19739). DLS receives grant funding from Arthritis Research UK and the National Institute for Health Research. In the last 3 years he has received honoraria (under £1,000) from Merck, Sharp and Dohme, UCB Pharma and Bristol Myers Squibb.

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of Medical and Molecular Genetics, 8th Floor Tower Wing, Guy’s HospitalKing’s College LondonLondonUK
  2. 2.Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, 1st Floor, New Hunt’s House, Guy’s CampusKing’s College LondonLondonUK
  3. 3.Department of Rheumatology, 3rd Floor, Weston Education CentreKing’s College HospitalLondonUK

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