Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis
Both the innate and adaptive immune responses are targeted by current RA treatments, but these treatments do not achieve consistent sustained disease remission. Protein kinase inhibitors represent a promising new therapeutic target, owing to their influence on downstream signalling and oral bioavailability. Fostamatinib (R788) has shown ACR20 responses of 67–72% in MTX inadequate responder patients at doses of 100mg bd and 150mg bd. However, the results in biologic non-responder patients were not convincing and no significant difference was shown versus placebo. In addition, toxicity concerns were raised in some trials, warranting further investigation to assess the impact of long-term use of this SYK inhibitor. The authors conclude that whilst fostamatinib did not show efficacy in the biologic non-responder population, post hoc subgroup analysis of these data suggests that further study is warranted. They add that literature from oncology research suggests that patients strongly prefer oral medication where efficacy is equivalent.