title: Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis.
abstract: Ruxolitinib (INCB018424) is the first potent, selective, oral inhibitor of JAK1 and 2 being developed for clinical use. Its major cellular and systemic effects are proliferation inhibition, apoptosis induction and reduction in cytokine plasma levels, all mediated by the drug's inhibition of JAKs' ability to phosphorylate STAT. In initial clinical trials of its use in myelofibrosis, ruxolitinib exhibited durable efficacy in reduction of splenomegaly and alleviation of constitutional symptoms. Patients also showed weight gain and improvement in general physical condition. The dose-limiting toxicity was thrombocytopenia. In preliminary findings of a Phase III trial in patients with primary, postpolycythemia-vera, or postessential-thrombocythemia myelofibrosis, administration at an initial dosage of 15 or 20 mg twice daily led to a spleen-volume response rate (≥ 35% reduction at 24 weeks) of 41.9 versus 0.7% for placebo (p < 0.0001); furthermore, 45.9% of the ruxolitinib recipients had ≥ 50% improvement in symptom score (on the modified Myelofibrosis Symptom Assessment Form version 2.0) versus 5.3% for placebo (p < 0.0001). Ruxolitinib recipients also showed improvement in parameters of quality of life.
authors.affiliation: Department of Hematology, University Hospital Merkur, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Alen
authors.initials: A
authors.lastname: Ostojic
authors.forename: Radovan
authors.initials: R
authors.lastname: Vrhovac
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D016896:Treatment Outcome
chemical_list: D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053613:Janus Kinase 1; D053614:Janus Kinase 2