Polycythemia vera: current pharmacotherapy and future directions.

In the past, management of polycythemia vera (PV) was built upon a cornerstone of control over erythrocytosis, through therapeutic phlebotomy, as well as the use of low-dose aspirin. Historically, selected patients were managed with additional cytoreductive therapies to decrease the risk of vascular events, with the recognition that these therapies likely did not impede progression.
Recent clinical trials have demonstrated, in a randomized fashion, that optimal control of the hematocrit to target levels < 45% are important for decreasing the risk of vascular events. We are identifying that our historical set of cytoreductive agents, such as hydroxyurea, may be replaced in the future. The first candidate is pegylated interferon alpha-2a, which is demonstrating the ability to control vascular events and control extended hematopoiesis, while potentially having impact on fibrotic progression and Janus kinase 2 (JAK2) V1617F mutant allele burden. Ruxolitinib, as well as other JAK2 inhibitors in development, are demonstrating that this class of agents is making a very meaningful impact on the risk of vascular events in PV, controlling expanded hematopoiesis, as well as helping with symptomatic burden.
Future goals include attaining a better understanding of the specific roles of JAK inhibitor therapy and whether their use in combination with standard therapies offers greater efficacy than single agents alone.
AuthorsBenjamin Hensley, Holly Geyer, Ruben Mesa
JournalExpert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 14 Issue 5 Pg. 609-17 (Apr 2013) ISSN: 1744-7666 [Electronic] England
PMID23480062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Alkylating Agents
  • Hematologic Agents
  • INCB018424
  • Interferon-alpha
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Recombinant Proteins
  • peginterferon alfa-2a
  • Polyethylene Glycols
  • JAK2 protein, human
  • Janus Kinase 2
  • Aspirin
  • Hydroxyurea
  • Alkylating Agents (therapeutic use)
  • Aspirin (therapeutic use)
  • Hematocrit
  • Hematologic Agents (adverse effects, therapeutic use)
  • Hematopoiesis (drug effects)
  • Humans
  • Hydroxyurea (therapeutic use)
  • Interferon-alpha (therapeutic use)
  • Janus Kinase 2 (antagonists & inhibitors, metabolism)
  • Polycythemia Vera (blood, complications, diagnosis, drug therapy)
  • Polyethylene Glycols (therapeutic use)
  • Predictive Value of Tests
  • Protein Kinase Inhibitors (therapeutic use)
  • Pyrazoles (therapeutic use)
  • Recombinant Proteins (therapeutic use)
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

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