Ruxolitinib (Jakafi): A twice-daily oral kinase inhibitor indicated for the treatment of myelofibrosis

On November 16, 2011, FDA approved ruxolitinib (Jakafi), a twice-daily tablet, indicated for the treatment of myelofibrosis. Ruxolitinib is a kinase inhibitor, specifically targeting Janus Associated Kinases (JAKs) 1 and 2 that mediate the signaling of cytokines and growth factors relevant to hematopoiesis and immune function. JAKs 1 and 2 initiate recruitment of signal transducers and activators of transcription to the cytokine receptors, which ultimately modulates gene expression.

Efficacy. Ruxolitinib's efficacy was established in 2 randomized, phase 3 trials in patients presenting with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia-myelofibrosis. Study 1 was a double-blind, placebo-controlled (n=309) trial for patients refractory to or not candidates for available therapy. Study 2 was an open-label trial (n=219) comparing ruxolitinib to the best available therapy. The primary efficacy end points were the proportion of patients who achieved a 35% or greater reduction in spleen volume from baseline, at 24 and 48 weeks for study 1 and study 2, respectively. In both studies, ruxolitinib was found to be more efficacious than placebo in study 1 and best available therapy in study 2.

Safety. The safety of ruxolitinib was evaluated in 6 clinical studies (n=617) over a median duration of 10.9 months, involving (n=301) patients with myelofibrosis in two phase 3 studies. In clinical trials, the most common adverse events included bruising, dizziness, headache, urinary tract infections, weight gain, and flatulence. Ruxolitinib may cause hematologic adverse reactions consisting of thrombocytopenia, anemia, and neutropenia. A complete blood count (CBC) should be performed prior to initiation of therapy and every 2 to 4 weeks until doses are stabilized. Patients with a platelet count less than 200 X 10⁹/L will be more susceptible to developing thrombocytopenia. If thrombocytopenia does present while taking ruxolitinib, dosage reduction or discontinuation of treatment must be advised. Patients developing anemia may require blood transfusions and dosage modifications of ruxolitinib. Patients developing neutropenia (ANC less than 0.5 X 10⁹/L) should withhold ruxolitinib until symptoms resolve. Risk of infection via bacteria, myobacteria, fungal, or viral should be assessed prior to initiation of ruxolitinib. If signs or symptoms of an infection are present, appropriate treatment should be initiated before starting ruxolitinib therapy. Clinicians should inform patients of early signs and symptoms of herpes zoster and advise patients to seek treatment.