Effect of Janus kinase inhibition by tofacitinib on body composition and glucose metabolism

J Med Invest. 2018;65(3.4):166-170. doi: 10.2152/jmi.65.166.

Abstract

Tofacitinib is the first Janus Kinase (JAK) inhibitor to treat moderately to severely active RA. In this study, we investigated whether the effect of tofacitinib have any effects on body composition in mice and female patients with RA. Female C57BL/6 mice fed with a high-fat diet were treated with 30 mg/kg/day tofacitinib or vehicle for 70 days. Following treatment, trunk muscle, subcutaneous fat, and visceral fats were measured using X-ray computed tomography CT scan. Glucose tolerance and insulin sensitivity were assessed. In female RA patients treated with biological disease modified anti-rheumatic-drugs (biological DMARDs) or tofacitinib (n=4 per group), we also evaluated the body composition after 3 months from the start of treatment initiation using bioelectrical impedance analysis. Treatment with tofacitinib did not affect the body weight, and body composition in C57BL/6 mice. It also did not affect glucose, and insulin tolerance in mice. In patients with RA, treatment with biological DMARDs did not affect the body composition whereas the muscle mass was unchanged after receiving tofacitinib and the fat mass was significantly increased. J. Med. Invest. 65:166-170, August, 2018.

Keywords: Body composition; Rheumatoid arthritis; Tofacitinib.

MeSH terms

  • Adiposity / drug effects
  • Adult
  • Aged
  • Animals
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacology
  • Arthritis, Rheumatoid / drug therapy
  • Body Composition / drug effects*
  • Diet, High-Fat / adverse effects
  • Female
  • Glucose / metabolism*
  • Humans
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / pharmacology*
  • Lipolysis / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Piperidines / adverse effects
  • Piperidines / pharmacology*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology*
  • Pyrroles / adverse effects
  • Pyrroles / pharmacology*
  • Weight Gain / drug effects

Substances

  • Antirheumatic Agents
  • Janus Kinase Inhibitors
  • Piperidines
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • Glucose