TY - JOUR
T1 - Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers
T2 - A randomized placebo-controlled trial
AU - Mehta, Nehal N.
AU - Shin, Daniel B.
AU - Joshi, Aditya A.
AU - Dey, Amit K.
AU - Armstrong, April W.
AU - Duffin, Kristina Callis
AU - Fuxench, Zelma Chiesa
AU - Harrington, Charlotte L.
AU - Hubbard, Rebecca A.
AU - Kalb, Robert E.
AU - Menter, Alan
AU - Rader, Daniel J.
AU - Reilly, Muredach P.
AU - Simpson, Eric L.
AU - Takeshita, Junko
AU - Torigian, Drew A.
AU - Werner, Thomas J.
AU - Troxel, Andrea B.
AU - Tyring, Stephen K.
AU - Vanderbeek, Suzette Baez
AU - Van Voorhees, Abby S.
AU - Playford, Martin P.
AU - Ahlman, Mark A.
AU - Alavi, Abass
AU - Gelfand, Joel M.
N1 - Funding Information:
This study was supported by grants (National Heart, Lung, and Blood Institute R01-HL111293, K24-AR-064310) and by an unrestricted grant from AbbVie (to the Trustees of the University of Pennsylvania). Dr Mehta is supported by National Institutes of Health Intramural Research Program (Z01 HL-06193). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication.
Funding Information:
Dr Mehta is a full-time US Government Employee and receives research grants to the National Heart, Lung, and Blood Institute (NHLBI) from AbbVie, Janssen, Cel-gene, and Novartis. Dr Gelfand in the past 12 months has served as a consultant for Coherus (DSMB), Dermira, Janssen Biologics, Merck (DSMB), Novartis Corp, Regeneron, Dr. Reddy’s Laboratories, Sanofi and Pfizer Inc, receiving honoraria; and receives research grants (to the Trustees of the University of Pennsylvania) from Abbvie, Janssen, Novartis Corp, Regeneron, Sanofi, Celgene, and Pfizer Inc; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly and Abbvie. Dr Gelfand is a co-patent holder of resiquimod for treatment of cutaneous T cell lymphoma. Dr Takeshita receives a research grant from Pfizer Inc (to the Trustees of the University of Pennsylvania) and has received payment for continuing medical education work related to psoriasis that was supported indirectly by Eli Lilly. A.B. Troxel is a co-patent holder of resiquimod for treatment of cutaneous T cell lymphoma. Dr Tyring conducts clinical studies sponsored by the following companies: Abbvie/ BI; Celgene; Coherus; Dermira; Eli Lilly; Janssen; Leo; Merck; Novartis; Pfizer; Regeneron/Sanofi; and Valeant. He is a speaker for Abbvie, Eli Lilly, Janssen, Leo, Novartis, Pfizer, Regeneron/Sanofi, and Valeant. Dr Armstrong has received research grants and honorarium from AbbVie, Celgene, Janssen, Novartis, Eli Lilly, Regeneron, Sanofi, and Valeant and has participated in continuing medical education work related to psoriasis that was indirectly supported by Eli Lilly and AbbVie. Dr Duffin has received grant/research/clinical trial support from Amgen, Abbvie, Celgene, Eli Lilly, Janssen, Bristol-Myers Squibb, Stiefel, Novartis, and Pfizer over the last 24 months. Additionally, Dr Duffin has served as a consultant/ on the advisory boards for Amgen, Abbvie, Celgene, Eli Lilly, Janssen, Bristol-My-ers Squibb, Stiefel, Novartis, and Pfizer. Dr Chiesa Fuxench has no conflicts of interest. However, she was being funded, at the time, by a research grant from the National Psoriasis Foundation and a training grant from the National Institutes of Health. Dr Hubbard receives grant funding from the National Institutes of Health and Patient-Centered Outcomes Research Institute. Dr Rader is the co-founder of Vascular Strategies and holds equity in the company. Dr Kalb has received grants/research funding from AbbVie, Amgen, Boehringer Ingelheim, Janssen-Ortho Inc, Merck & Co, Inc, and Novartis Pharmaceuticals Corp over the last 24 months. During this time frame, he has also served as a consultant honoraria for Dermira, Janssen-Ortho Inc, Sun Pharmaceutical Industries Ltd, and a DSMB member honoraria for Eli Lilly and Co. Dr Simpson has served as a consultant for AbbVie, Anacor, Celgene, Dermira, Genentech, Leo, Glaxo Smith Kline, Pfizer, Regeneron, Sanofi-Genzyme, Menlo, and Eli Lilly in the last 24 months. During this time frame, he has also acted as the primary investigator for the following sponsored trials: Anacor, Celgene, Chugai, Dermira, Eli Lilly, Genentech, MedIm-mune, Merck, Novartis, Regeneron, Roivant, Tioga, and Vanda. Dr Torigian is the co-founder of Quantitative Radiology Solutions LLC. Dr Van Voorhees has served on the advisory board of Celgene, Dermira, Allergan, Merck, Pfizer, Aqua, Astra Zeneca, Jannsen, Amgen, Leo, Allergan, and Lilly. For Novartis and AbbVie, Dr Van Voorhees acts as a consultant as well as serves on the board. Dr Van Voor-hees has received a portion of ex-spouse pension from Merck. Dr Menter in the last 24 months has served on the advisory board for AbbVie, Allergan, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Inc, and LEO Pharma. He has also worked as a consultant for AbbVie, Allergan, Amgen, Eli Lilly, Galderma, Janssen Biotech, Inc, LEO Pharma, Novartis, Pfizer, Vitae, and Xenoport. Additionally, he has acted as an investigator for AbbVie, Allergan, Amgen, Anacor, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Janssen Biotech, Inc, LEO Pharma, Merck, Neothetics, Novartis, Pfizer, Regeneron, Symbio/Maruho, and Xenoport. He also serves as a speaker for AbbVie, Amgen, Janssen Biotech, Inc, and LEO Pharma. He has received compensation in the form of grants from AbbVie, Allergan, Am-gen, Anacor, Boehringer Ingelheim, Celgene, Dermira, Janssen Biotech, Inc, LEO Pharma, Merck, Neothetics, Novartis, Pfizer, Regeneron, Symbio/Maruho, and Xenoport. He has also received honoraria from AbbVie, Allergan, Amgen, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen Biotech, Inc, LEO Pharma, Novartis, Pfizer, Vitae, and Xenoport. The other authors report no conflicts.
Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - BACKGROUND: Psoriasis is a chronic inflammatory disease associated with dyslipidemia, cardiovascular events, and mortality. We aimed to assess and compare the effect of treatment of moderate-to-severe psoriasis with adalimumab or phototherapy on vascular inflammation and cardiovascular biomarkers. METHODS AND RESULTS: Randomized, double-blind, trial of adalimumab, phototherapy, and placebo (1:1:1) for 12 weeks, with crossover to adalimumab for 52 weeks total. Outcomes included vascular inflammation by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and biomarkers of inflammation, insulin resistance, and lipoproteins. Ninety-seven patients were randomized, 92 completed the randomized controlled trial portion; 81 entered the adalimumab extension with 61 completing 52 weeks of adalimumab. There was no difference in change in vascular inflammation at week 12 in the adalimumab group (change compared with placebo, 0.64%; 95% confidence interval, −5.84% to 7.12%) or the phototherapy group (−1.60%; 95% confidence interval, −6.78% to 3.59%) or after 52-week adalimumab treatment (0.02% compared with initiation; 95% confidence interval, −2.85% to 2.90%). Both adalimumab and phototherapy decreased inflammation by serum CRP, interleukin-6. Only adalimumab reduced tumor necrosis factor and glycoprotein acetylation at 12 and 52 weeks. Neither had an impact on metabolic markers (insulin, adiponectin, and leptin). Only phototherapy increased high-density lipoprotein-p at 12 weeks. At 52-week of adalimumab cholesterol efflux and high-density lipoprotein-p were reduced. CONCLUSIONS: Adalimumab reduced key markers of inflammation including glycoprotein acetylation compared with phototherapy with no effect on glucose metabolism and vascular inflammation, and potential adverse effects on high-density lipoprotein. Glycoprotein acetylation improvement may partially explain the beneficial effects of adalimumab seen in observational studies. Larger studies with more detailed phenotyping of vascular disease should assess the comparative differences in the effects of adalimumab and phototherapy seen in our study.
AB - BACKGROUND: Psoriasis is a chronic inflammatory disease associated with dyslipidemia, cardiovascular events, and mortality. We aimed to assess and compare the effect of treatment of moderate-to-severe psoriasis with adalimumab or phototherapy on vascular inflammation and cardiovascular biomarkers. METHODS AND RESULTS: Randomized, double-blind, trial of adalimumab, phototherapy, and placebo (1:1:1) for 12 weeks, with crossover to adalimumab for 52 weeks total. Outcomes included vascular inflammation by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and biomarkers of inflammation, insulin resistance, and lipoproteins. Ninety-seven patients were randomized, 92 completed the randomized controlled trial portion; 81 entered the adalimumab extension with 61 completing 52 weeks of adalimumab. There was no difference in change in vascular inflammation at week 12 in the adalimumab group (change compared with placebo, 0.64%; 95% confidence interval, −5.84% to 7.12%) or the phototherapy group (−1.60%; 95% confidence interval, −6.78% to 3.59%) or after 52-week adalimumab treatment (0.02% compared with initiation; 95% confidence interval, −2.85% to 2.90%). Both adalimumab and phototherapy decreased inflammation by serum CRP, interleukin-6. Only adalimumab reduced tumor necrosis factor and glycoprotein acetylation at 12 and 52 weeks. Neither had an impact on metabolic markers (insulin, adiponectin, and leptin). Only phototherapy increased high-density lipoprotein-p at 12 weeks. At 52-week of adalimumab cholesterol efflux and high-density lipoprotein-p were reduced. CONCLUSIONS: Adalimumab reduced key markers of inflammation including glycoprotein acetylation compared with phototherapy with no effect on glucose metabolism and vascular inflammation, and potential adverse effects on high-density lipoprotein. Glycoprotein acetylation improvement may partially explain the beneficial effects of adalimumab seen in observational studies. Larger studies with more detailed phenotyping of vascular disease should assess the comparative differences in the effects of adalimumab and phototherapy seen in our study.
KW - Adalimumab
KW - Biomarkers
KW - Inflammation
KW - Psoriasis
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UR - http://www.scopus.com/inward/citedby.url?scp=85048422916&partnerID=8YFLogxK
U2 - 10.1161/CIRCIMAGING.117.007394
DO - 10.1161/CIRCIMAGING.117.007394
M3 - Article
C2 - 29776990
AN - SCOPUS:85048422916
SN - 1941-9651
VL - 11
JO - Circulation. Cardiovascular imaging
JF - Circulation. Cardiovascular imaging
IS - 6
M1 - e007394
ER -