Is spleen tyrosine kinase inhibition an effective therapy for patients with RA?

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.