The pathogenesis of RA is a complex and ever-changing landscape but amid the 
chaos of the disease process we have found effective treatment regimes. However, 
our current therapeutics, although targeting various components of both the 
innate and adaptive immune response, do not result in disease remission. Protein 
kinase inhibitors are attractive targets due to their ability to influence 
downstream signalling and their oral bioavailability. Fostamatinib (R788) 
inhibits spleen tyrosine kinase (Syk) and has been in clinical trials involving 
both MTX inadequate responders (MTX-IRs) and biologic inadequate responders. 
Studies on the MTX-IR population revealed ACR20 responses of 67-72% at higher 
doses (150 mg bd and 100 mg bd), ACR50 responses of 43-57% and ACR70 responses 
of 28-40%. The trial in the biologic non-responder population showed no 
efficacy, however, post hoc analyses of the data suggested that a further trial 
in this population is warranted. The most common adverse events included 
gastrointestinal effects, hypertension, neutropenia and transaminitis. Many 
adverse effects were dose responsive and hypertension was amenable to treatment. 
Upper respiratory tract infections were more likely at higher doses, but no 
serious infections with tuberculosis, fungi or opportunistic infections were 
reported. The oral availability of these agents makes them attractive treatment 
options for our patients, although the literature from the oncology field 
suggests that patients will only choose the oral route if efficacy is 
equivalent. Long-term follow-up studies are ongoing and will be critical for 
rare side effects. The role of these agents in our current arsenal is unclear 
and economic analyses are awaited.