title: Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I.
abstract: BACKGROUND
  In the COMFORT (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy)-I study, the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib provided significant reductions in splenomegaly, improvements in myelofibrosis (MF)-related symptoms, and a survival advantage relative to placebo in patients with intermediate-2 or high-risk MF. In this post hoc analysis, we assessed the effects of ruxolitinib treatment on measures of metabolic and nutritional status.
  
  
  METHODS
  Patients were randomized to receive ruxolitinib (n = 155; 15 or 20 mg twice a day for patients with baseline platelet counts of 100-200 × 10(9)/L or > 200 × 10(9)/L, respectively) or placebo (n = 154). The primary end point was the proportion of patients with a ≥ 35% spleen volume reduction from baseline to week 24. A secondary end point was the proportion of patients with ≥ 50% improvement in Total Symptom Score (TSS) from baseline to week 24, measured using the modified Myelofibrosis Symptom Assessment Form version 2.0. Weight, cholesterol, and albumin were measured at specified time points throughout the study.
  
  
  RESULTS
  Compared with placebo, ruxolitinib treatment was associated with increased weight (mean change: 3.9 kg vs. -1.9 kg), total cholesterol (mean percentage change: 26.4% vs. -3.3%), and albumin levels (mean percentage change: 5.8% vs. -1.7%) at week 24; sustained improvements were observed with longer-term ruxolitinib therapy. Relative to placebo, increases in mean weight, total cholesterol, and albumin levels were observed with ruxolitinib treatment regardless of the degree of spleen volume and TSS reductions at 24 weeks.
  
  
  CONCLUSIONS
  Treatment with ruxolitinib improved measures of metabolic and nutritional status of patients with intermediate-2 or high-risk MF.
authors: Mayo Clinic, Scottsdale, AZ. Electronic address: mesa.ruben@mayo.edu.
authors: Ruben A
authors: RA
authors: Mesa
authors: The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Srdan
authors: S
authors: Verstovsek
authors: Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors: Vikas
authors: V
authors: Gupta
authors: Icahn School of Medicine at Mount Sinai, New York, NY.
authors: John O
authors: JO
authors: Mascarenhas
authors: Medical College of Wisconsin, Froedtert Hospital, Milwaukee, WI.
authors: Ehab
authors: E
authors: Atallah
authors: Incyte Corporation, Wilmington, DE.
authors: Timothy
authors: T
authors: Burn
authors: Incyte Corporation, Wilmington, DE.
authors: William
authors: W
authors: Sun
authors: Incyte Corporation, Wilmington, DE.
authors: Victor
authors: V
authors: Sandor
authors: Stanford Cancer Institute, Stanford, CA.
authors: Jason
authors: J
authors: Gotlib
mesh_terms: D015415:Biomarkers; D001835:Body Weight; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D009570:Nitriles; D009929:Organ Size; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D012709:Serum Albumin; D013154:Spleen / Q000033:anatomy & histology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D012709:Serum Albumin; C540383:ruxolitinib; D002784:Cholesterol; D053612:Janus Kinases
keywords: Albumin; Cachexia; Cholesterol; JAK inhibitor; Weight