SAT-091 Metabolic Effects of JAK1/2 Inhibition in Patients with Myeloproliferative Neoplasms

Background: Ruxolitinib is a JAK1/2 inhibitor that is FDA approved to treat certain myeloproliferative neoplasms (MPNs), including myelofibrosis (MF) and polycythemia vera (PV). The JAK family kinases are targeted in cancers due to their role in cytokine receptor signal transduction, and are also key intermediates in growth hormone, leptin and prolactin receptor signaling. Clinical trials have reported that ruxolitinib treatment was associated with weight gain, but other metabolic consequences remain unknown. Aim: We aimed to determine the metabolic consequences of JAK1/2 inhibition with ruxolitinib in patients with MPN in the clinical setting. Methods: IRB approval was obtained, and we identified patients from an electronic medical record (EMR) based database who began treatment with ruxolitinib for MPN from December 2011 to December 2016. Data collected from EMRs included age, gender, weight, height, systolic and diastolic blood pressure (SBP, DBP), medications, co-morbidities, random serum glucose, and lipid profile. We compared parameters from baseline (prior to initiating ruxolitinib) to 72±8 weeks after starting treatment. Baseline and 72 week data were compared using the Wilcoxon signed rank test. Results: 129 patients were initially identified, of which 71 had data available for weight, and at least one other metabolic parameter of interest at baseline and 72 weeks. Patient characteristics were as follows: 49.3% male; mean age at initiation of treatment was 64.6±SD11.1 years; indications for treatment were MF (77%), PV(17%), other MPNs (6%). Mean baseline weight was 73.6±16.9kg, and was 78.3±8.9kg at 72 weeks (n=71, p<0.001). Mean body mass index (BMI) at baseline was 25.6±4.6kg/m(2), and 27.3±5.4kg/m(2) at 72 weeks (n=68, p<0.001).The BMI (kg/m(2)) distribution for underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obese (>30) at baseline were: 3%, 43%, 41%, and 13%, respectively; at 72 weeks it was 1%, 40%, 34%, and 28%, respectively (p=0.002). At 72 weeks,19% moved up a BMI class from baseline. Next, we investigated the effect of ruxolitinib treatment on BP and glucose concentrations. SBP was 124±15 mmHg at baseline and 129±18 mmHg at 72 weeks, (p=0.042, n=71). DBP was not different between baseline and 72 weeks. Glucose at baseline was 99±28mg/dL and 101±29mg/dL at 72 weeks (p=0.015, n=59). There was no change in the percent of patients with hyperglycemia (glucose ≥200mg/dL) or on treatment for diabetes at baseline (13.6%) and 72 weeks (13.6%). An insufficient number of patients had lipid data available for analysis. Conclusions: Systemic JAK1/2 inhibition was associated with weight gain, the development of obesity, and increased SBP in this cohort of patients. As pharmacological JAK1 and 2 inhibitors are developed and more widely used, it is important to gain a greater understanding of their long-term metabolic consequences.