The Effect of Tildrakizumab on Cardiometabolic Risk Factors in Psoriasis by Metabolic Syndrome Status: Post Hoc Analysis of Two Phase 3 Trials (ReSURFACE 1 and ReSURFACE 2)

August 2020 | Volume 19 | Issue 8 | Original Article | 703 | Copyright © August 2020

Published online July 22, 2020

M. Alan Menter MDa, Nehal N. Mehta MD MSCE FAHAb, Mark G. Lebwohl MDc, Alice B. Gottlieb MD PhDd, Alan M. Mendelsohn MDe, Stephen J. Rozzo PhDe, Craig Leonardi MDf

aDivision of Dermatology, Baylor Scott & White, and Texas A&M College of Medicine, Dallas, TX BNational Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD cDepartment of Dermatology, Mount Sinai Hospital, New York, NY dDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY eSun Pharmaceutical Industries, Inc., Princeton, NJ fCentral Dermatology and Saint Louis University School of Medicine, St. Louis, MO

Background: Metabolic syndrome (MetS) is the most prevalent comorbidity in psoriasis and increases the risk of cardiovascular disease, diabetes, and mortality. Assessment of impacts of biologic therapies on cardiometabolic risk factors are relatively limited. This study evaluated the effect of tildrakizumab on cardiometabolic risk factors in patients with moderate to severe plaque psoriasis and stratified by MetS status.
Methods: In this post hoc analysis of reSURFACE 1/2, tildrakizumab 100 and 200 mg were continuously administered to patients with moderate to severe plaque psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Mean and mean percent changes from baseline were assessed for fasting serum glucose, low/high-density lipoprotein-cholesterol, total cholesterol, triglyceride levels, body weight, and blood pressure at week 64/52 for reSURFACE 1 and 2, respectively, in patients with and without MetS.
Results: A total of 369 patients in reSURFACE 1 and 2 received continuous tildrakizumab 100 mg and 330 received tildrakizumab 200 mg; 21.4% and 20.3% in reSURFACE 1 and 2, respectively, had MetS. At week 64/52, mean changes in cardiometabolic risk factors from baseline did not significantly differ regardless of MetS status. Numerically larger mean decreases in fasting glucose, triglycerides, and systolic blood pressure following tildrakizumab 100 mg and in systolic and diastolic blood pressure following tildrakizumab 200 mg were observed in patients with MetS relative to those without MetS.
Conclusions: Changes in cardiometabolic disease risk factors following tildrakizumab treatment were limited. Risk factors were not increased in patients with MetS vs without MetS.

J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5337


Metabolic syndrome (MetS) is a combination of factors including dysglycemia, raised blood pressure (BP), dyslipidemia (raised triglycerides [TG] and lowered high-density lipoprotein cholesterol [HDL-C]), raised fasting glucose (FG), and central obesity1 that increase the risk of cardiovascular (CV) disease,1 diabetes,1 and mortality.2 In patients with moderate-to-severe plaque psoriasis, MetS is the most prevalent comorbidity.3-5 Relative to the general population, patients with psoriasis have a higher prevalence of MetS with a reported pooled odds ratio (95% confidence interval [CI]) of 2.14 (1.84, 2.48) from 35 studies.6

The presence of MetS risk factors may influence future treatment decisions, as they reduce the efficacy of some medications in psoriasis, including anti-tumor necrosis factor alpha (TNF-α) and anti–interleukin (IL)-17 based biologic therapies,7-9 or have neutral effects with other treatments.10,11 Both ustekinumab and TNF-α antagonists have been associated with weight gain during treatment.12-15 Adalimumab, etanercept, and ustekinumab were associated with a 9% increase in serum triglyceride levels in patients with psoriasis.16 Biologic therapies for psoriasis may increase body weight and total cholesterol, triglycerides, and low density lipoprotein in patients not taking statins.12,17 Higher rates of risk for complications of preexisting obesity, hypertension, and/or hypertriglyceridemia, as well as higher rates of cardiovascular disease and new or worsening diabetes mellitus are anticipated in patients with psoriasis and concomitant MetS relative to patients without MetS while receiving biologic therapy.1 There are no published data evaluating biologic therapy-induced changes in cardiometabolic risk factors based on concomitant MetS status in psoriasis.