TITLE

Ruxolitinib In the Treatment of Myelofibrosis

AUTHOR(S)
Yang, Lily P. H.; Keating, Gillian M.
PUB. DATE
September 2012
SOURCE
Drugs;2012, Vol. 72 Issue 16, p2117
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Ruxolitinib is a selective inhibitor of Janus kinases (JAK) 1 and 2, which are involved in the signalling pathway of various cytokines and growth factors essential to haematopoiesis. JAK 1 and 2 are implicated in the development of myelofibrosis, as well as other haematological malignancies. Ruxolitinib is the first agent approved for the treatment of myelofibrosis. In a randomized, double-blind, placebo-controlled, multicentre trial (COMFORT-I) in patients with myelofibrosis, significantly more ruxolitinib than placebo recipients achieved a >35% reduction in spleen volume (primary endpoint) at 24 weeks. In a randomized, open-label, multicentre trial (COMFORT- II) in patients with myelofibrosis, significantly more ruxolitinib than best available therapy recipients achieved the same primary endpoint at 48 weeks. Significantly more ruxolitinib than placebo recipients achieved a >50% reduction in Total Symptom Score at 24 weeks in COMFORT-I. Ruxolitinib generally improved health-related quality-of-life scores, while best available therapy was generally associated with worsened scores at 48 weeks in COMFORT-II. In COMFORT-I, overall survival data appeared to favour ruxolitinib over placebo; of note, most placebo recipients had crossed over to receive ruxolitinib. In COMFORT- II, a significant difference in overall survival between ruxolitinib and best available therapy was not shown; this trial was not powered to detect such a difference. In clinical trials in patients with myelofibrosis, ruxolitinib was generally associated with an acceptable tolerability profile. In the placebo-controlled trial, the most commonly reported grade 3 or 4 adverse events in ruxolitinib recipients were thrombocytopenia, anaemia and neutropenia. These haematological adverse events were mainly managed with dosage interruptions/reductions and/or transfusions, and rarely resulted in discontinuation.
ACCESSION #
83364640

 

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