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Researchers Examine Metabolic Effects of Ruxolitinib

Allison Inserro
A recent study found that treatment with a systemic JAK1/2 inhibitor was associated with weight gain, the development of obesity, and increased systolic blood pressure.
A  recent study examined the metabolic effects of ruxolitinib in patients with myeloproliferative neoplasms (MPNs). Previous studies have reported that ruxolitinib treatment was linked with weight gain, but other metabolic effects are unknown.

Ruxolitinib, a tyrosine kinase inhibitor (TKI) that inhibits Janus kinase (JAK) 1/2, is approved by the FDA to treat certain 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.

In this study, researchers identified patients from a database of electronic medical records (EMRs). The patients had started 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, comorbidities, random serum glucose, and lipid profile.

Parameters were compared 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.

Of the 129 patients identified, 71 had data available for weight, and at least 1 other metabolic parameter of interest at baseline and 72 weeks. Patients were 49.3% male with a mean age at start of treatment of 64.6 (11.1) years. Disease indications for treatment were MF (77%), PV (17%), and other MPNs (6%).

Mean baseline weight was 73.6 (16.9) kg, and was 78.3 (8.9) kg at 72 weeks (n = 71, P <.001). Mean body mass index (BMI) at baseline was 25.6 (4.6) kg/m2, and 27.3 (5.4) kg/m2 at 72 weeks (n = 68, P <.001).

The BMI (kg/m2) distribution for underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), and obese (>30) at baseline were: 3%, 43%, 41%, and 13%, respectively. At 72 weeks it was 1%, 40%, 34%, and 28%, respectively (P = .002). At 72 weeks, 19% of the patients moved up a BMI class from baseline.

The effect of ruxolitinib was also examined for treatment on blood pressure and glucose concentrations. SBP was 124/15 mmHg at baseline and 129/18 mmHg at 72 weeks, (P = .042, n = 71). DBP was not different between baseline and 72 weeks.

Glucose at baseline was 99 (28) mg/dL and 101 (29) mg/dL at 72 weeks (P = .015, n = 59). There was no change in the percent of patients with hyperglycemia (glucose ≥200 mg/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.

In this group of patients, treatment with a systemic JAK1/2 inhibition was associated with weight gain, the development of obesity, and increased SBP.

The researchers said it is important to get an improved understanding of these therapies as they become more widely used.

Reference

Sapre M, Tremblay D, Leiter A, et al. SAT-091 metabolic effects of JAK1/2 inhibition in patients with myeloproliferative neoplasms. J Endocr Soc. 2019; 3(1) doi: 10.1210/js.2019-SAT-091.

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