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Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk.

Authors
  • Podolanczuk, Anna
  • Lazarus, Alan H
  • Crow, Andrew R
  • Grossbard, Elliot
  • Bussel, James B
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
Apr 02, 2009
Volume
113
Issue
14
Pages
3154–3160
Identifiers
DOI: 10.1182/blood-2008-07-166439
PMID: 19096013
Source
Medline
License
Unknown

Abstract

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).

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