TY - JOUR
T1 - Metabolic Effects of JAK1/2 Inhibition in Patients with Myeloproliferative Neoplasms
AU - Sapre, Manali
AU - Tremblay, Douglas
AU - Wilck, Eric
AU - James, Annie
AU - Leiter, Amanda
AU - Coltoff, Alexander
AU - Koshy, Anita G.
AU - Kremyanskaya, Marina
AU - Hoffman, Ronald
AU - Mascarenhas, John O.
AU - Gallagher, Emily J.
N1 - Funding Information:
M.S. received funding from the Icahn School of Medicine at Mount Sinai Summer Student Investigator Award; A.C. received support from the American Society of Hematology Honors Award, E.J.G. received support from the National Institutes of Health/National Cancer Institute K08CA190770, the Department of Medicine and the Tisch Cancer Institute at Mount Sinai.
Funding Information:
J.O.M. has received research funding from Incyte, Novartis, Roche, Merck, CTI Biopharma, Janssen, PharmaEssentia, and is on the clinical trial steering committee for Incyte, CTI Biopharma and Celgene. M.K. has received research funding from Incyte, Constellation, Celgene, Blueprint and fees from La Jolla Pharmaceuticals. M.S., A.C., A.L., D.T., A.J., E.W. and A.G. have no conflicts of interest. E.J.G. served on advisory board for Novartis.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Ruxolitinib is an FDA approved janus kinase (JAK)1/2 inhibitor used to treat myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera. We aimed to determine the metabolic consequences of ruxolitinib treatment in patients with MPNs. We performed a retrospective single-center cohort study utilizing an electronic medical record based database of patients who began treatment with ruxolitinib for MPNs from January 2010 to March 2017. We also examined the effects of ruxolitinib on adipose tissue JAK/STAT signaling in a mouse model. 127 patients were identified, of which 69 had data available for weight, and at least one other parameter of interest before, and 72 weeks after starting ruxolitinib. Mean baseline weight was 73.9 ± 17.0 kg, and 78.54 ± 19.1 kg at 72 weeks (p < 0.001). 50% of patients gained >5% body weight. Baseline body mass index (BMI) was 25.8 ± 4.8 kg/m2, and 27.5 ± 5.5 kg/m2 at 72 weeks (p < 0.001). Patients treated with ruxolitinib had a higher systolic blood pressure, serum AST, and ALT at 72 weeks, compared with baseline (p = 0.03, p = 0.01, p = 0.04, respectively). In mice, ruxolitinib decreased basal and GH-stimulated STAT5 phosphorylation in adipose tissue. As pharmacological JAK1/2 inhibitors are being developed and used in clinical practice, it is important to understand their long-term metabolic consequences.
AB - Ruxolitinib is an FDA approved janus kinase (JAK)1/2 inhibitor used to treat myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera. We aimed to determine the metabolic consequences of ruxolitinib treatment in patients with MPNs. We performed a retrospective single-center cohort study utilizing an electronic medical record based database of patients who began treatment with ruxolitinib for MPNs from January 2010 to March 2017. We also examined the effects of ruxolitinib on adipose tissue JAK/STAT signaling in a mouse model. 127 patients were identified, of which 69 had data available for weight, and at least one other parameter of interest before, and 72 weeks after starting ruxolitinib. Mean baseline weight was 73.9 ± 17.0 kg, and 78.54 ± 19.1 kg at 72 weeks (p < 0.001). 50% of patients gained >5% body weight. Baseline body mass index (BMI) was 25.8 ± 4.8 kg/m2, and 27.5 ± 5.5 kg/m2 at 72 weeks (p < 0.001). Patients treated with ruxolitinib had a higher systolic blood pressure, serum AST, and ALT at 72 weeks, compared with baseline (p = 0.03, p = 0.01, p = 0.04, respectively). In mice, ruxolitinib decreased basal and GH-stimulated STAT5 phosphorylation in adipose tissue. As pharmacological JAK1/2 inhibitors are being developed and used in clinical practice, it is important to understand their long-term metabolic consequences.
UR - http://www.scopus.com/inward/record.url?scp=85074979561&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-53056-x
DO - 10.1038/s41598-019-53056-x
M3 - Article
C2 - 31719581
AN - SCOPUS:85074979561
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 16609
ER -