Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies

Ann Rheum Dis. 2018 Jul;77(7):988-995. doi: 10.1136/annrheumdis-2017-212461. Epub 2018 Feb 20.

Abstract

Objectives: Lipid profiles are altered by active disease in patients with rheumatoid arthritis (RA) and may be further modified by treatment with Janus kinase inhibitors and other disease-modifying antirheumatic drugs.

Methods: Lipid data were analysed from phase II and III studies of 4 mg (n=997) and 2 mg (n=479) oral baricitinib administered once daily in patients with moderate-to-severe active RA. Lipoprotein particle size and number and GlycA were evaluated with nuclear magnetic resonance in one phase III study. The effect of statin therapy on lipid levels was evaluated in patients on statins at baseline and in patients who initiated statins during the study.

Results: Treatment with baricitinib was associated with increased levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides, but no significant change in LDL-C:HDL-C ratio. Lipid levels plateaued after 12 weeks of treatment. Baricitinib treatment increased large LDL and decreased small, dense LDL particle numbers and GlycA. Lipid changes from baseline were not significantly different between baseline statin users and non-users. In patients who initiated statin therapy during the study, LDL-C, triglycerides (baricitinib 4 mg only) and apolipoprotein B decreased to pre-baricitinib levels; HDL-C and apolipoprotein A-I levels remained elevated.

Conclusions: Baricitinib was associated with increased LDL-C, HDL-C and triglyceride levels, but did not alter the LDL-C:HDL-C ratio. Evaluation of cardiovascular event rates during long-term treatment is warranted to further characterise these findings and their possible clinical implications.

Trial registration number: NCT00902486, NCT01469013, NCT01185353, NCT01721044, NCT01721057, NCT01711359, NCT01710358, NCT01885078.

Keywords: DMARDs (biologics); lipids; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antirheumatic Agents / administration & dosage
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Azetidines / administration & dosage*
  • Cholesterol, HDL / drug effects*
  • Cholesterol, LDL / drug effects*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Lipid Metabolism / drug effects*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Reference Values
  • Severity of Illness Index
  • Sulfonamides / administration & dosage*
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Azetidines
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Sulfonamides
  • baricitinib

Associated data

  • ClinicalTrials.gov/NCT01469013
  • ClinicalTrials.gov/NCT01885078
  • ClinicalTrials.gov/NCT01721057
  • ClinicalTrials.gov/NCT00902486
  • ClinicalTrials.gov/NCT01721044
  • ClinicalTrials.gov/NCT01711359
  • ClinicalTrials.gov/NCT01185353
  • ClinicalTrials.gov/NCT01710358