Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis

Robert Wolk, Ehrin J. Armstrong, Peter R. Hansen, Bruce Thiers, Shuping Lan, Anna M. Tallman, Mandeep Kaur, Svitlana Tatulych

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. Objective: The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Methods: Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. Results: At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. Conclusion: While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639].

Original languageEnglish (US)
JournalJournal of Clinical Lipidology
DOIs
StateAccepted/In press - 2017
Externally publishedYes

Fingerprint

Psoriasis
HDL Lipoproteins
Lipids
Serum Amyloid A Protein
Cholesterol
HDL Cholesterol
Phosphatidylcholine-Sterol O-Acyltransferase
Janus Kinases
Aryldialkylphosphatase
Serum
Lipid Metabolism
C-Reactive Protein
LDL Cholesterol
Lipoproteins
tofacitinib
Triglycerides
Antioxidants
Biomarkers
Macrophages
Placebos

Keywords

  • Cardiovascular risk
  • HDL function
  • Lipid levels
  • Lipid metabolism
  • Lipoproteins
  • Psoriasis
  • Tofacitinib

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

Cite this

Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis. / Wolk, Robert; Armstrong, Ehrin J.; Hansen, Peter R.; Thiers, Bruce; Lan, Shuping; Tallman, Anna M.; Kaur, Mandeep; Tatulych, Svitlana.

In: Journal of Clinical Lipidology, 2017.

Research output: Contribution to journalArticle

Wolk, Robert ; Armstrong, Ehrin J. ; Hansen, Peter R. ; Thiers, Bruce ; Lan, Shuping ; Tallman, Anna M. ; Kaur, Mandeep ; Tatulych, Svitlana. / Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis. In: Journal of Clinical Lipidology. 2017.
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abstract = "Background: Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. Objective: The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Methods: Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. Results: At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. Conclusion: While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639].",
keywords = "Cardiovascular risk, HDL function, Lipid levels, Lipid metabolism, Lipoproteins, Psoriasis, Tofacitinib",
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T1 - Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis

AU - Wolk, Robert

AU - Armstrong, Ehrin J.

AU - Hansen, Peter R.

AU - Thiers, Bruce

AU - Lan, Shuping

AU - Tallman, Anna M.

AU - Kaur, Mandeep

AU - Tatulych, Svitlana

PY - 2017

Y1 - 2017

N2 - Background: Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. Objective: The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Methods: Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. Results: At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. Conclusion: While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639].

AB - Background: Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. Objective: The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Methods: Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. Results: At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. Conclusion: While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639].

KW - Cardiovascular risk

KW - HDL function

KW - Lipid levels

KW - Lipid metabolism

KW - Lipoproteins

KW - Psoriasis

KW - Tofacitinib

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