Ruxolitinib: A Review in Polycythaemia Vera

Ruxolitinib (Jakavi^®, Jakafi^®) is an orally administered, first-in-class Janus Kinase (JAK) 1 and 2 inhibitor that was recently approved for the treatment of patients with polycythaemia vera (PV) who have responded inadequately to or are intolerant of hydroxyurea. By inhibiting JAK 1 and 2, ruxolitinib reduces hyperactive JAK-signal transducers and activators of transcription (STAT) signalling that is implicated in the pathogenesis of PV. This article briefly reviews the pharmacology of the drug, focusing on its clinical use in patients with PV. In the phase III RESPONSE trial in PV patients who had an inadequate response to or unacceptable adverse effects from hydroxyurea, ruxolitinib was superior to best available therapy in reducing haematocrit without phlebotomy and reducing spleen size after 32 weeks of treatment. Ruxolitinib was also associated with reducing leukocyte and platelet counts and improving symptoms. Patient follow-up demonstrated that response to ruxolitinib was durable, including preliminary results after up to 80 weeks of treatment. The drug is generally well tolerated, although mild to moderate anaemia, thrombocytopenia and lymphopenia were common in the RESPONSE trial. These effects can usually be managed with dosage modification and did not lead to therapy discontinuation in the RESPONSE trial. Thus, for a subgroup of PV patients for whom few treatment options have existed previously, ruxolitinib provides a valid option.