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Ruxolitinib for the treatment of myelofibrosis: its clinical potential
(7387) Total Article Views
Authors: Ostojic A, Vrhovac R, Verstovsek S
Published Date March 2012
Volume 2012:8 Pages 95 - 103
|Received:||03 January 2012|
|Accepted:||11 February 2012|
|Published:||01 March 2012|
1Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb, Zagreb, Croatia; 2Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
Abstract: Ruxolitinib is an orally bioavailable, selective Janus kinase (JAK) 1 and 2 inhibitor approved for the treatment of myelofibrosis (MF), a bone marrow disease in which the JAK pathway is dysregulated, leading to impaired hematopoiesis and immune function. By inhibiting JAK1 and JAK2, ruxolitinib modulates cytokine-stimulated intracellular signaling. In a phase II clinical trial in patients with MF, ruxolitinib recipients exhibited durable reductions in spleen size, reductions in circulating pro-inflammatory cytokines, improvements in physical activity, weight gain, and alleviation of symptoms (including constitutional symptoms) in patients with and without JAK2 mutation. These findings were confirmed by two phase III clinical MF studies, in which a greater proportion of ruxolitinib recipients achieved a spleen volume reduction of ≥35% from baseline at week 24, compared with placebo in one study (41.9% versus 0.7%; P < 0.0001) and with best available therapy in the other (31.9% versus 0%; P < 0.0001). Alleviation of MF symptoms and improvements in quality of life were also significantly greater in ruxolitinib recipients. Overall survival of patients treated with ruxolitinib was significantly longer than of those receiving the placebo. Owing to risks of potentially serious adverse effects, eg, myelosuppression, ruxolitinib should be used under close physician supervision. Longer follow-up of the phase III MF studies is needed to reach firm conclusions regarding ruxolitinib’s capacity to modify the natural disease course.
Keywords: myelofibrosis, JAK2 inhibitor, ruxolitinib
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