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Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis.
J Clin Lipidol 2017 Sep - Oct; 11(5):1243-1256JC

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].

Authors+Show Affiliations

Pfizer Inc, Groton, CT, USA. Electronic address: robert.wolk@pfizer.com.Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Denver, CO, USA.Department of Cardiology, Herlev and Gentofte Hospital, Hellerup, Denmark.Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, SC, USA.Pfizer Inc, Groton, CT, USA.Pfizer Inc, New York, NY, USA.Pfizer Inc, Collegeville, PA, USA.Pfizer Inc, Groton, CT, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28751001

Citation

Wolk, Robert, et al. "Effect of Tofacitinib On Lipid Levels and Lipid-related Parameters in Patients With Moderate to Severe Psoriasis." Journal of Clinical Lipidology, vol. 11, no. 5, 2017, pp. 1243-1256.
Wolk R, Armstrong EJ, Hansen PR, et al. Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis. J Clin Lipidol. 2017;11(5):1243-1256.
Wolk, R., Armstrong, E. J., Hansen, P. R., Thiers, B., Lan, S., Tallman, A. M., ... Tatulych, S. (2017). Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis. Journal of Clinical Lipidology, 11(5), pp. 1243-1256. doi:10.1016/j.jacl.2017.06.012.
Wolk R, et al. Effect of Tofacitinib On Lipid Levels and Lipid-related Parameters in Patients With Moderate to Severe Psoriasis. J Clin Lipidol. 2017;11(5):1243-1256. PubMed PMID: 28751001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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, Y1 - 2017/06/24/ PY - 2016/12/12/received PY - 2017/05/30/revised PY - 2017/06/17/accepted PY - 2017/7/29/pubmed PY - 2018/5/15/medline PY - 2017/7/29/entrez KW - Cardiovascular risk KW - HDL function KW - Lipid levels KW - Lipid metabolism KW - Lipoproteins KW - Psoriasis KW - Tofacitinib SP - 1243 EP - 1256 JF - Journal of clinical lipidology JO - J Clin Lipidol VL - 11 IS - 5 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]. SN - 1933-2874 UR - https://www.unboundmedicine.com/medline/citation/28751001/Effect_of_tofacitinib_on_lipid_levels_and_lipid_related_parameters_in_patients_with_moderate_to_severe_psoriasis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1933-2874(17)30356-2 DB - PRIME DP - Unbound Medicine ER -