Abstract
Despite the success of biologic therapeutic agents that target cytokines and lymphocytes, clinical needs remain unmet in the treatment of rheumatoid arthritis (RA). The development of small-molecule inhibitors that can block critical immune signal-transduction pathways are of particular interest as novel therapies for RA. Spleen tyrosine kinase (SYK) subserves the function of Fc receptors and the B-cell receptor; as such, it is attractive as a potential therapeutic target. Weinblatt and colleagues recently performed a proof-of-concept study, which demonstrated that inhibition of SYK reduced RA disease activity and levels of disease-relevant biomarkers. Dose-limiting adverse effects include diarrhea, neutropenia and hypertension, which result from both target-dependent and off-target effects. This novel study provides the first evidence that SYK could be a useful therapeutic target in RA.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Cha HS et al. (2006) A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated gene expression in synoviocytes. J Pharmacol Exp Ther 317: 571–578
Braselmann S et al. (2006) R406, an orally available spleen tyrosine kinase inhibitor blocks Fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther 319: 998–1008
Weinblatt ME et al. (2008) Treatment of rheumatoid arthritis with a SYK kinase inhibitor: a 12-week, randomized, placebo-controlled trial. Arthritis Rheum 58: 3309–3318
Bussel JB et al. (2007) R935788: a phase II, single center, open-label, efficacy and safety, ascending dose, pilot study for the treatment of adult immune thrombocytopenic purpura (ITP). Blood (ASH Annual Meeting Abstracts) 110: 1310
van Heeckeren WJ et al. (2007) Hypertension, proteinuria, and antagonism of vascular endothelial growth-factor signaling: clinical toxicity, therapeutic target, or novel biomarker? J Clin Oncol 25: 2993–2995
Williams W et al. (2008) A randomized placebo-controlled study of INCB018424, a selective Janus kinase 1 & 2 (JAK1&2) inhibitor in rheumatoid arthritis (RA) [abstract #714]. Arthritis Rheum 58: S431
Wilkinson B et al. (2008) Coadministration of an oral JAK inhibitor CP-690,550 and methotrexate is well tolerated in patients with rheumatoid arthritis [abstract #353]. Arthritis Rheum 58: S297
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
IB McInnes is a consultant for and has received grant/research support from Bristol-Myers Squibb, Roche, Schering-Plough and Wyeth, and has received speaker's honoraria from Schering-Plough.
Rights and permissions
About this article
Cite this article
Hueber, A., McInnes, I. Is spleen tyrosine kinase inhibition an effective therapy for patients with RA?. Nat Rev Rheumatol 5, 130–131 (2009). https://doi.org/10.1038/ncprheum1025
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ncprheum1025