Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers: A randomized placebo-controlled trial

Nehal N. Mehta, Daniel B. Shin, Aditya A. Joshi, Amit K. Dey, April W. Armstrong, Kristina Callis Duffin, Zelma Chiesa Fuxench, Charlotte L. Harrington, Rebecca A. Hubbard, Robert E. Kalb, Alan Menter, Daniel J. Rader, Muredach P. Reilly, Eric Simpson, Junko Takeshita, Drew A. Torigian, Thomas J. Werner, Andrea B. Troxel, Stephen K. Tyring, Suzette Baez VanderbeekAbby S. Van Voorhees, Martin P. Playford, Mark A. Ahlman, Abass Alavi, Joel M. Gelfand

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere007394
JournalCirculation: Cardiovascular Imaging
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2018

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Psoriasis
Blood Vessels
Randomized Controlled Trials
Biomarkers
Placebos
Inflammation
Phototherapy
Therapeutics
Acetylation
Glycoproteins
Confidence Intervals
HDL Lipoproteins
Adalimumab
Adiponectin
Fluorodeoxyglucose F18
Dyslipidemias
Leptin
Vascular Diseases
HDL Cholesterol
Lipoproteins

Keywords

  • Adalimumab
  • Biomarkers
  • Inflammation
  • Psoriasis

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers : A randomized placebo-controlled trial. / Mehta, Nehal N.; Shin, Daniel B.; Joshi, Aditya A.; Dey, Amit K.; Armstrong, April W.; Duffin, Kristina Callis; Fuxench, Zelma Chiesa; Harrington, Charlotte L.; Hubbard, Rebecca A.; Kalb, Robert E.; Menter, Alan; Rader, Daniel J.; Reilly, Muredach P.; Simpson, Eric; Takeshita, Junko; Torigian, Drew A.; Werner, Thomas J.; Troxel, Andrea B.; Tyring, Stephen K.; Vanderbeek, Suzette Baez; Van Voorhees, Abby S.; Playford, Martin P.; Ahlman, Mark A.; Alavi, Abass; Gelfand, Joel M.

In: Circulation: Cardiovascular Imaging, Vol. 11, No. 6, e007394, 01.06.2018.

Research output: Contribution to journalArticle

Mehta, NN, Shin, DB, Joshi, AA, Dey, AK, Armstrong, AW, Duffin, KC, Fuxench, ZC, Harrington, CL, Hubbard, RA, Kalb, RE, Menter, A, Rader, DJ, Reilly, MP, Simpson, E, Takeshita, J, Torigian, DA, Werner, TJ, Troxel, AB, Tyring, SK, Vanderbeek, SB, Van Voorhees, AS, Playford, MP, Ahlman, MA, Alavi, A & Gelfand, JM 2018, 'Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers: A randomized placebo-controlled trial', Circulation: Cardiovascular Imaging, vol. 11, no. 6, e007394. https://doi.org/10.1161/CIRCIMAGING.117.007394
Mehta, Nehal N. ; Shin, Daniel B. ; Joshi, Aditya A. ; Dey, Amit K. ; Armstrong, April W. ; Duffin, Kristina Callis ; Fuxench, Zelma Chiesa ; Harrington, Charlotte L. ; Hubbard, Rebecca A. ; Kalb, Robert E. ; Menter, Alan ; Rader, Daniel J. ; Reilly, Muredach P. ; Simpson, Eric ; Takeshita, Junko ; Torigian, Drew A. ; Werner, Thomas J. ; Troxel, Andrea B. ; Tyring, Stephen K. ; Vanderbeek, Suzette Baez ; Van Voorhees, Abby S. ; Playford, Martin P. ; Ahlman, Mark A. ; Alavi, Abass ; Gelfand, Joel M. / Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers : A randomized placebo-controlled trial. In: Circulation: Cardiovascular Imaging. 2018 ; Vol. 11, No. 6.
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abstract = "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.",
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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

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.

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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