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
Tildrakizumab is a high-affinity, humanized, immunoglobulin G1κ, anti–IL‐23p19 monoclonal antibody approved for treatment of moderate to severe plaque psoriasis. Tildrakizumab specifically blocks IL-23 function without affecting the IL-12 heterodimer. 18 Recently, Lebwohl et al. showed for the first time that tildrakizumab efficacy and safety in patients with moderate to severe psoriasis did not differ based on concomitant MetS status through 52 weeks.19 Elevated IL-23 levels in patients with CV disease—which has been linked to increased morbidity and mortality—suggests inhibition of IL-23 via tildrakizumab may have the potential to directly or indirectly impact CV risk factors.20 Here, we evaluate changes in 6 cardiometabolic risk factors for MetS after tildrakizumab treatment based on MetS status at baseline—FG, low-density lipoprotein-cholesterol (LDL-C)/HDL-C, total cholesterol (TC), TG, body weight, and BP.
Methods for this pooled, post hoc analysis of 2 phase 3, 3-part, double-blind, randomized, placebo-controlled studies (reSURFACE 1 [NCT01722331] and reSURFACE 2 [NCT01729754]) were previously reported.19,21 Briefly, patients were ≥18 years of age with moderate to severe plaque psoriasis (body surface area involvement ≥10%, Physician's Global Assessment score ≥3, and Psoriasis Area and Severity Index score ≥12). All protocols were reviewed and approved by local institutional review boards or ethics panels and conducted according to the Declaration of Helsinki. A placebo treatment arm was included for the first 12 weeks of these studies.
Only patients who continuously received tildrakizumab 100 or 200 mg at weeks 0 and 4 and then every 12 weeks throughout the base study periods for a total of 64 weeks for reSURFACE 1 and 52 weeks for reSURFACE 2 were included; patients receiving placebo during the first 12 weeks of the base study period prior to reassignment to tildrakizumab were not included. A retrospective clinical evaluation of baseline MetS status was conducted19 as defined by National Cholesterol Education Program Adult Treatment Panel III criteria.22 Body mass index, calculated from body weight, was used as a proxy for waist circumference data, as this parameter was not collected. Cardiometabolic factors FG, LDL-C/HDL-C, TC, TG, body weight, and systolic/diastolic BP (SBP/DBP) were measured in all patients who received tildrakizumab 100 or 200 mg. The last body weight measurement was at week 28.
Results for week 64 (reSURFACE 1) and week 52 (reSURFACE 2) were combined by tildrakizumab dose. Mean (95% CI) values of cardiometabolic factors stratified by MetS status within each treatment cohort, mean/median absolute and percent change (95% CI) from baseline to weeks 64/52 were calculated.
Of 1862 patients entering reSURFACE 1 (n = 772) and reSURFACE 2 (n = 1090), 369 received tildrakizumab 100 mg and 330 received tildrakizumab 200 mg continuously throughout the base study, with no placebo exposure or dose modifications. In total, 79 (21.4%) and 67 (20.3%) patients receiving tildrakizumab 100 and 200 mg, respectively, met MetS criteria. Baseline demographics and disease characteristics were similar between treatments.19
As expected, patients with MetS had lower baseline HDL-C; higher baseline body weight, body mass index, TG, FG, and SBP/DBP (Table 1); and prevalence of CV disease and diabetes mellitus19 compared with patients without MetS. Six (4.1%) patients with MetS (n = 5 tildrakizumab 100 mg; n = 1 tildrakizumab 200 mg) and 25 (4.5%) patients without MetS (n = 12 tildrakizumab 100 mg; n = 13 tildrakizumab 200 mg) did not complete week 64/52.