TY - JOUR
T1 - A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S)
AU - Gelfand, Joel M.
AU - Shin, Daniel B.
AU - Duffin, Kristina Callis
AU - Armstrong, April W.
AU - Blauvelt, Andrew
AU - Tyring, Stephen K.
AU - Menter, Alan
AU - Gottlieb, Scott
AU - Lockshin, Benjamin N.
AU - Simpson, Eric L.
AU - Kianifard, Farid
AU - Sarkar, Rajendra Prasad
AU - Muscianisi, Elisa
AU - Steadman, Jennifer
AU - Ahlman, Mark A.
AU - Playford, Martin P.
AU - Joshi, Aditya A.
AU - Dey, Amit K.
AU - Werner, Thomas J.
AU - Alavi, Abass
AU - Mehta, Nehal N.
N1 - Funding Information:
The authors are grateful to Jennifer Steadman and Suzette Baez Vanderbeek for their expert project management and to the patients who volunteered for this study. The authors would like to thank Bitumani Borah and Mohammad Fahad Haroon (Novartis Health Care Pvt Ltd, Hyderabad, India) for providing medical writing and editorial assistance. The study was approved by the Institutional Review Boards of University of Utah and University of Southern California. Conceptualization: JG, AA, NM, FK, JS; Data Curation: DS, AAJ, TW, MP; Formal Analysis: JG, DS, NM, AAJ, RPS, FK; Funding Acquisition: JG, NM; Investigation: JG, KCD, AA, AB, ST, SG, BL, ES, AM, TW, MP; Methodology: JG, DS, MA, EM, FK, AD; Project Administration: JG, JS, TW; Resources: JG, AA, NM, MA, AD; Software: DS, RPS; Supervision: JG, FK, EM; Validation: DS; Visualization: DS, RPS, FK; Writing - Original Draft: JG; Writing - Review and Editing: DS, KCD, AA, AB, ST, AM, SG, BL, ES, FK, RPS, EM, JS, MA, MP, AJ, AD, TW, AA, NM
Funding Information:
Gelfand served as a consultant for BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, UCB (DSMB), Sanofi, and Pfizer, receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from AbbVie, Boehringer Ingelheim, Janssen, Novartis, Celgene, Ortho Dermatologics, and Pfizer; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Eli Lilly, Ortho Dermatologics, and Novartis. Gelfand is a deputy editor for the Journal of Investigative Dermatology, receiving honoraria from the Society for Investigative Dermatology. Gelfand’s laboratory replicated the Novartis analyses independently and conducted the exploratory analyses. Duffin has received research grants from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sienna Biopharmaceuticals, Stiefel Laboratories, and UCB; has received consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Ortho Dermatologic, Pfizer, Sienna Biopharmaceuticals, Stiefel Laboratories, and UCB; and is on the speaker's bureau for Novartis. Armstrong has served as investigator, advisor, and/or consultant to Leo, AbbVie, UCB, Janssen, Novartis, Eli Lilly, Sun, Dermavant, BMS, Regeneron Pharmaceuticals, Inc, Sanofi U.S., Dermira, Modmed, and Ortho Dermatologics, Inc. Blauvelt has served as a scientific advisor and/or clinical study investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, FLX Bio, Forte, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Meiji, Merck Sharp & Dohme, Novartis, Ortho, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, and Vidac and as a paid speaker for AbbVie, Regeneron, and Sanofi Genzyme. Tyring has conducted studies sponsored by the producer of secukinumab. Menter has received compensation from or served as an investigator, consultant, advisory board member, or speaker for Abbott Labs, AbbVie, Allergan, Amgen, Anacor, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Janssen, Leo, Merck & Co, Neothetics, Novartis, Pfizer, Regeneron, Sienna, Symbio/Maruho, UCB, Vitae, and Xenoport. Gottlieb is currently serving as consultant, advisory board member, speaker for Janssen, Celgene, Bristol-Myers Squibb, Beiersdorf, AbbVie, UCB, Novartis, Incyte, Lilly, Reddy Labs, Valeant, Dermira, Allergan, Sun Pharmaceutical Industries, Xbiotech, Leo, and Avotres Therapeutics, and has received research/educational grants from Janssen, Incyte, UCB, Novartis, Lilly Xbiotech, and Boeringer Ingelheim. Lockshin reports personal fees from Lilly, Novartis, Janssen, and Abbott; has served as a speaker for Novartis, Eli Lilly, and AbbVie; conducted research for Celgene, AbbVie, Novartis, Eli Lilly, and Strata; and served as a consultant for Novartis, Eli Lilly, AstraZeneca, and AbbVie. Simpson reports grants from Eli Lilly, Kyowa Hakko Kirin, Leo Pharmaceutical, Merck, Pfizer, and Regeneron, and personal fees from Menlo Therapeutics, Valeant, Novartis, Eli Lilly, Galderma, Dermira, Sanofi Genzyme, Pfizer, Regeneron, and Leo Pharmaceuticals. F Kianifard, E Muscianisi, and J Steadman are employees and/or stockholders of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. R Sarkar is an employee of Novartis Healthcare Private Limited, Hyderabad, India. Mehta is a full-time US Government Employee and receives research grants to NHLBI from AbbVie, Janssen, Celgene and Novartis. Gelfand in the past has served as a consultant for Amgen, Coherus (DSMB), Dermira, Eli Lilly, Janssen Biologics, Leo Pharma, Merck (DSMB), Novartis Corp, Regeneron, Dr. Reddy’s labs, Sanofi and Pfizer Inc, receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from AbbVie, Janssen, Novartis Corp, Regeneron, Sanofi, Celgene, and Pfizer; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Eli Lilly and AbbVie. Shin, Ahlman, Playford, Joshi, Dey, Werner, and Alavi have nothing to disclose. This study is funded by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Publisher Copyright:
© 2020 The Authors
PY - 2020/9
Y1 - 2020/9
N2 - Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose–positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was –0.053 (95% confidence interval = –0.169 to 0.064; P = 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P = 0.0063) and ferritin (P = 0.0354), and an increase in fetuin-A (P = 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.
AB - Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose–positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was –0.053 (95% confidence interval = –0.169 to 0.064; P = 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P = 0.0063) and ferritin (P = 0.0354), and an increase in fetuin-A (P = 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.
UR - http://www.scopus.com/inward/record.url?scp=85082809951&partnerID=8YFLogxK
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U2 - 10.1016/j.jid.2020.01.025
DO - 10.1016/j.jid.2020.01.025
M3 - Article
C2 - 32088207
AN - SCOPUS:85082809951
SN - 0022-202X
VL - 140
SP - 1784-1793.e2
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -