Ruxolitinib in patients with polycythemia vera resistant and/or intolerant to hydroxyurea:European observational study

Background: Hydroxyurea (HU) is a commonly used first-line treatment in patients with polycythemia vera (PV). However, approximately 15%–24% of PV patients report intolerance and resistance to HU. Methods: This phase IV, European, real-world, observational study assessed the efficacy and safety of ruxolitinib in PV patients who were resistant and/or intolerant to HU, with a 24-month follow-up. The primary objective was to describe the profile and disease burden of PV patients. Results: In the 350 enrolled patients, 70% were &gt;60 years old. Most patients (59.4%) had received ≥1 phlebotomy in the 12 months prior to the first dose of ruxolitinib. Overall, 68.2% of patients achieved hematocrit control with 92.3% patients having hematocrit &lt;45% and 35.4% achieved hematologic remission at month 24. 85.1% of patients had no phlebotomies during the study. Treatment-related adverse events were reported in 54.3% of patients and the most common event was anemia (22.6%). Of the 10 reported deaths, two were suspected to be study drug-related. Conclusion: This study demonstrates that ruxolitinib treatment in PV maintains durable hematocrit control with a decrease in the number of phlebotomies in the majority of patients and was generally well tolerated.</p

Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due To Combined Estrogen Plus Progestin Therapy

OBJECTIVE: To examine whether tissue factor pathway inhibitor or acquired activated protein C resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. APPROACH AND RESULTS: Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women’s Health Initiative randomized trial of estrogen plus progestin therapy (EPT). After multivariable covariate adjustment, both baseline tissue factor pathway activity (p=0.01) and activated protein C resistance (p=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and activated protein C resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared to placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased activated protein C resistance but these changes did not appear to modify or mediate the effect of estrogen plus progestin on CHD risk. CONCLUSIONS: Tissue factor pathway inhibitor activity and activated protein C resistance are related to CHD risk in women, but may not explain the increased CHD risk due to EPT. The data from this study do not support the clinical utility of measuring these hemostatic factors to help stratify risk prior to hormone therap