The objective of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to normalize blood levels and hence minimize thrombotic episodes. For patients with ET and PV at high risk of vascular problems, the most often utilized cytoreductive alternatives are hydroxyurea (HU) and interferon-α (IFN-α). The Myeloproliferative Disorders Research Consortium 112 study compared HU to pegylated IFN-α (PEG) in treatment-naive, high-risk patients with ET/PV. The primary outcome was the 12-month complete response (CR) rate. A total of 168 patients received treatment for an average of 81.0 weeks. 

At 12 months, the CR for HU was 37%, while the CR for PEG was 35% (P=.80). At 24 to 36 months, CR ranged from 20% to 17% for HU and from 29% to 33% for PEG. At 24 months, PEG resulted in a higher decrease in JAK2V617F, although histopathologic responses were more common with HU. Thrombotic events and disease progression were uncommon in both groups, although PEG was associated with a higher rate of grade 3/4 adverse events (46% vs. 28%). There was no significant difference in CR rates between HU and PEG after 12 months of therapy. According to this study, PEG and HU are both effective therapies for PV and ET. PEG was more successful in regulating blood counts and lowering driver mutation load with extended therapy, but HU induced higher histopathologic responses. Despite the differences, no drug reduced thrombotic events or disease progression in high-risk ET/PV patients.