Of mice and men: An open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk Academic Article uri icon


MeSH Major

  • Disease Models, Animal
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Oxazines
  • Protein-Tyrosine Kinases
  • Purpura, Thrombocytopenic, Idiopathic
  • Pyridines


  • To determine whether inhibition of Syk would be useful in FcgammaR-dependent cytopenias such as immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia, mouse models were used to evaluate efficacy of R406, an inhibitor of Syk function, in treating cytopenia. Both disease models responded favorably to treatment, with amelioration of ITP being more dramatic. Thus, phase 2 clinical trial was initiated to study the effects of Syk inhibition in humans with ITP. Sixteen adults with chronic ITP were entered into an open-label, single-arm cohort dose-escalation trial beginning with 75 mg and escalating as high as 175 mg twice daily. Doses were increased until a persistent response was seen, toxicity occurred, or 175 mg twice daily was reached. Eight patients achieved persistent responses with platelet counts greater than 50 x 10(9)/L (50 000 mm(3)) on more than 67% (actually 95%) of their study visits, including 3 who had not persistently responded to thrombopoietic agents. Four others had nonsustained responses. Mean peak platelet count exceeded 100 x 10(9)/L (100 000 mm(3)) in these 12 patients. Toxicity was primarily GI-related with diarrhea (urgency) and vomiting; 2 patients had transaminitis. In conclusion, inhibition of Syk was an efficacious means of increasing and maintaining the platelet count in half the patients with chronic refractory ITP. (ClinicalTrials.gov, no. NCT00706342).

publication date

  • April 2, 2009



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1182/blood-2008-07-166439

PubMed ID

  • 19096013

Additional Document Info

start page

  • 3154

end page

  • 60


  • 113


  • 14