Original article
Ixekizumab treatment shows a neutral impact on cardiovascular parameters in patients with moderate-to-severe plaque psoriasis: Results from UNCOVER-1, UNCOVER-2, and UNCOVER-3

https://doi.org/10.1016/j.jaad.2018.02.074Get rights and content

Background

The impact of ixekizumab treatment for psoriasis on cardiovascular-related parameters in patients is unknown.

Objective

To investigate cardiovascular-related parameters in patients with psoriasis treated with ixekizumab.

Methods

In phase 3 trials, patients with moderate-to-severe psoriasis were randomized and treated with placebo, ixekizumab, or etanercept during the induction period (weeks 0-12; UNCOVER-1, UNCOVER-2, and UNCOVER-3). At week 12, responders were rerandomized to receive placebo or ixekizumab through the maintenance period (weeks 12-60; UNCOVER-1 and UNCOVER-2). Laboratory measures (fasting lipid profiles, glucose level, or high-sensitivity C-reactive protein [hsCRP] level), weight, blood pressure, and electrocardiograms were obtained through 60 weeks.

Results

Baseline parameters were within normal ranges with the exception of elevated triglyceride and hsCRP levels. After maintenance dosing, no significant changes were observed versus placebo for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglyceride, apolipoprotein A1, apolipoprotein B, or fasting glucose levels or for systolic/diastolic blood pressure at 60 weeks. Importantly, low-density lipoprotein–to–high-density lipoprotein ratios remained stable during the induction and maintenance periods. HsCRP concentrations were significantly reduced versus placebo at 12 weeks and remained reduced at 60 weeks, although not significantly. Although transient changes were observed for some parameters during the induction period, these changes did not persist into the maintenance period.

Limitations

A lack of echocardiogram evaluations.

Conclusions

Ixekizumab had a neutral impact on cardiovascular-related parameters in patients with psoriasis.

Key words

cardiovascular
cholesterol
hsCRP
IL-17A
ixekizumab
psoriasis
UNCOVER

Abbreviations used

HDL
high-density lipoprotein
hsCRP
high-sensitivity C-reactive protein
IL-17A
interleukin 17A
LDL
low-density lipoprotein
MACEs
major adverse cardiovascular events

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Funding sources: Supported by Eli Lilly and Company.

Disclosure: Dr Egeberg has received research funding from Pfizer, Eli Lilly and Company, the Danish National Psoriasis Foundation, and the Kgl Hofbundtmager Aage Bangs Foundation, as well as honoraria for serving as a consultant and/or speaker from Leo Pharma, Samsung Bioepis, Pfizer, Eli Lilly and Company, Novartis, Galderma, and Janssen Pharmaceuticals. Dr Wu has served as an investigator for AbbVie, Amgen, Eli Lilly and Company, Janssen, Novartis, and Regeneron. Dr Solomon has served as a consultant for and/or received honoraria from Eli Lilly and Company, Genentech, Castle Biosciences, and Samumed, and he is an employee of Ameriderm Research, which has received clinical trial grants from Allergan, Altana, Anacor, Apotex, AstraZeneca, Asubio, Barrier, Basilea, Bayer, Boehringer Ingelheim, Biocryst, Braintree, Centocor, Celtic, Chilter, Cipher, Clynsis, Concentrics, Covance, CuTech, Dermira, Dow, Eli Lilly and Company, Encorium, Epithany, Galderma, Genentech, Genomics, GlaxoSmithKline, Glenmark, Health Decisions, HedgePath Pharmaceutical, Hill, ICON, Incyte, Inventiv, Kendle International, Leo Pharmaceuticals, Manhattan, Maruho, MAVIS, Merck, Novartis, Noven, Novum, Omnicare, ParaPro Inc, Parexel, Peplin, Pfizer, PharmaNet, Polynoma, PPD Development, PRA, Premier, Pro Trials, Quintiles, Regeneron, Research Sample Bank, Rho, Roche, Sanofi-Aventis, SciQuus, Serentis, SGS, Steifel, Sterling Bio, Symbio, Taisho, Taro, Teva, Theraputics, TKL Research, Tolmar, Topaz, Vanda, and Worldwide Clinical Trials. Dr Korman has served as an investigator, grant reviewer, speaker or advisory board member for Abbvie, Amgen, Dermira, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Prothena, Regeneron, Sun, and Valeant. Drs Goldblum, Zhao, and Mallbris are full-time employees of Eli Lilly and Company and own stock in it.

This manuscript was prepared with the assistance of a medical writer who is a full-time employee of Eli Lilly and Company.

Portions of the results reported in this manuscript were previously presented in the form of an abstract and poster at the American Academy of Dermatology 75th Annual Meeting, Orlando, FL, March 5, 2017.

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© 2018 by the American Academy of Dermatology, Inc.