Weight Gain, Blood Pressure Rise Seen With JAK Inhibitor Therapy

By Megan Brooks

April 01, 2019

NEW YORK (Reuters Health) - Pharmacologic inhibition of Janus kinases (JAK) 1 and 2 is associated with significant weight gain and increased systolic blood pressure, according to a review of patients treated with the JAK1/2 inhibitor ruxolitinib.

"We recommend that patients who go on this medication and do have an increase in weight get a full metabolic workup," Dr. Emily Gallagher of Icahn School of Medicine at Mount Sinai, in New York City, noted in a phone interview with Reuters Health.

"Because cancer today is much more of a chronic disease and patients are surviving longer, we want to make sure we're not putting them at risk for other complications such as cardiovascular disease," said Dr. Gallagher.

She presented her research March 24 at the Endocrine Society's annual meeting in New Orleans.

Ruxolitinib is approved by the U.S. Food and Drug Administration (FDA) for certain myeloproliferative neoplasms (MPNs), including myelofibrosis (MF) and polycythemia vera (PV). In clinical trials, ruxolitinib was associated with some weight gain, but other metabolic consequences remain unknown.

"As JAK1 and 2 inhibitors are developed and more widely used, it is important to develop a greater understanding of their long-term metabolic consequences," Dr. Gallagher and colleagues note in their meeting poster.

To that end, the Mount Sinai team took a look back at 69 patients (35 women) with MPNs who started on ruxolitinib from 2010 to 2017 at Mount Sinai. The medical records had data on metabolic parameters up to one year prior to starting ruxolitinib and 72 weeks after starting the drug.

According to the records, average weight at baseline was 73.9 kg (162.9 lbs) and increased to 78.5 kg (173 lbs) at 72 weeks (P<0.001). Average body mass index (BMI) was 25.8 kg/m2 at baseline and increased to 27.5 kg/m2 at 72 weeks (P<0.001).

The BMI distribution for underweight, normal, overweight and obese at baseline was 2.9%, 41.2%, 41.2%, and 14.7%, respectively; at 72 weeks, it was 1.5%, 38.2%, 30.9%, and 29.4%, respectively.

"At least 50% of patients who take this medication gain a substantial amount of weight," Dr. Gallagher told Reuters Health. "The clinical trials reported a mean weight gain of about 3.9 kg but we found a weight gain of more than 5 to 10% of their baseline body weight which is a substantial amount of weight gain."

"What's also interesting," she said, "is we found an increase in systolic blood pressure and that obviously needs to be reproduced in a bigger cohort but that is potentially something to look out for that this medication could be associated with cardiovascular events."

Systolic BP was 124 mm Hg at baseline and 129 mm Hg after 72 weeks on ruxolitinib.

"We didn't have enough information to look at lipids and other metabolic parameters. The glucose in this sample was random glucose so it's not clear if it causes significant changes in glucose but the weight gain and increase in systolic blood pressure in itself are important findings. The change in blood pressure is not something described before," Dr. Gallagher noted.

As for liver enzymes, baseline and week-72 alanine aminotransferase (ALT) levels were 25.8 and 32.1 IU/L (P=0.013), respectively, and corresponding aspartate aminotransferase (AST) levels were 27.0 and 31.5 IU/L (P=0.041).

"Based on these results, it is important to monitor patients who are treated with JAK targeted therapy for the development of metabolic derangements including hyperglycemia, dyslipidemia, hypertension and hepatic steatosis," the authors conclude in their poster.

Incyte Corporation, which markets ruxolitinib at Jakafi, did not respond to a request for comment on the study findings by press time.

SOURCE: http://bit.ly/2CLdg5P

The Endocrine Society 2019.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: