Nehal N Mehta1, Daniel B Shin2, Aditya A Joshi3, Amit K Dey3, April W Armstrong4, Kristina Callis Duffin5, Zelma Chiesa Fuxench2, Charlotte L Harrington3, Rebecca A Hubbard6,7, Robert E Kalb8, Alan Menter9, Daniel J Rader10, Muredach P Reilly11, Eric L Simpson12, Junko Takeshita2,6,7, Drew A Torigian13, Thomas J Werner13, Andrea B Troxel6, Stephen K Tyring14, Suzette Baez Vanderbeek2, Abby S Van Voorhees15, Martin P Playford3, Mark A Ahlman16, Abass Alavi13, Joel M Gelfand17,6,7. 1. Cardiopulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (N.N.M., A.A.J., A.K.D., C.L.H., M.P.P.). nehal.mehta@nih.gov Joel.Gelfand@uphs.upenn.edu. 2. Department of Dermatology, Perelman School of Medicine (D.B.S., Z.C.F., J.T., S.B.V., J.M.G.). 3. Cardiopulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (N.N.M., A.A.J., A.K.D., C.L.H., M.P.P.). 4. University of Pennsylvania, Philadelphia. Department of Dermatology, University of Southern California, Los Angeles (A.W.A.). 5. Department of Dermatology, University of Utah, Salt Lake City (K.C.D.). 6. Department of Epidemiology and Biostatistics, Perelman School of Medicine (R.A.H., J.T., A.B.T., J.M.G.). 7. The Center for Clinical Epidemiology and Biostatistics (R.A.H., J.T., J.M.G.). 8. Department of Dermatology, Buffalo School of Medicine and Biomedical Sciences, State University of New York (R.E.K.). 9. Department of Dermatology, Baylor University Medical Center, Dallas, TX (A.M.). 10. Department of Genetics (D.J.R.). 11. Department of Cardiology, Division of Medicine, Vagelos College of Physician and Surgeons, and the Irving Institute for Clinical and Translational Research, Columbia University Irving Medical Center, New York, NY (M.P.R.). 12. Department of Dermatology, Oregon Health & Science University, Portland (E.L.S.). 13. Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia (D.A.T., T.J.W., A.A.). 14. Department of Dermatology, McGovern Medical School at Houston, TX (S.K.T.). 15. Department of Dermatology, Eastern Virginia Medical School, Norfolk (A.S.V.V.). 16. Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Research Center, Bethesda, MD (M.A.A.). 17. Department of Dermatology, Perelman School of Medicine (D.B.S., Z.C.F., J.T., S.B.V., J.M.G.) nehal.mehta@nih.gov Joel.Gelfand@uphs.upenn.edu.
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. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01866592 and NCT01553058.
RCT Entities:
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 adalimumabcholesterol 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. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01866592 and NCT01553058.
Authors: Paul M Ridker; Brendan M Everett; Tom Thuren; Jean G MacFadyen; William H Chang; Christie Ballantyne; Francisco Fonseca; Jose Nicolau; Wolfgang Koenig; Stefan D Anker; John J P Kastelein; Jan H Cornel; Prem Pais; Daniel Pella; Jacques Genest; Renata Cifkova; Alberto Lorenzatti; Tamas Forster; Zhanna Kobalava; Luminita Vida-Simiti; Marcus Flather; Hiroaki Shimokawa; Hisao Ogawa; Mikael Dellborg; Paulo R F Rossi; Roland P T Troquay; Peter Libby; Robert J Glynn Journal: N Engl J Med Date: 2017-08-27 Impact factor: 91.245
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Authors: Amit K Dey; Aditya A Joshi; Abhishek Chaturvedi; Joseph B Lerman; Tsion M Aberra; Justin A Rodante; Heather L Teague; Charlotte L Harrington; Joshua P Rivers; Jonathan H Chung; Mohammad Tarek Kabbany; Balaji Natarajan; Joanna I Silverman; Qimin Ng; Gregory E Sanda; Alexander V Sorokin; Yvonne Baumer; Emily Gerson; Ronald B Prussick; Alison Ehrlich; Lawrence J Green; Benjamin N Lockshin; Mark A Ahlman; Martin P Playford; Joel M Gelfand; Nehal N Mehta Journal: JAMA Cardiol Date: 2017-09-01 Impact factor: 14.676
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Authors: Kaisa M Mäki-Petäjä; Maysoon Elkhawad; Joseph Cheriyan; Francis R Joshi; Andrew J K Ostör; Frances C Hall; James H F Rudd; Ian B Wilkinson Journal: Circulation Date: 2012-10-24 Impact factor: 29.690
Authors: Margery A Connelly; James D Otvos; Irina Shalaurova; Martin P Playford; Nehal N Mehta Journal: J Transl Med Date: 2017-10-27 Impact factor: 5.531
Authors: Alexander V Sorokin; Kazuhiko Kotani; Youssef A Elnabawi; Amit K Dey; Aparna P Sajja; Shingo Yamada; Masashi Ueda; Charlotte L Harrington; Yvonne Baumer; Justin A Rodante; Joel M Gelfand; Marcus Y Chen; Aditya A Joshi; Martin P Playford; Alan T Remaley; Nehal N Mehta Journal: Circ Res Date: 2018-11-09 Impact factor: 17.367
Authors: Michael S Garshick; Michael Tawil; Tessa J Barrett; Charissa M Salud-Gnilo; Michael Eppler; Angela Lee; Jose U Scher; Andrea L Neimann; Sanja Jelic; Nehal N Mehta; Edward A Fisher; James G Krueger; Jeffrey S Berger Journal: Arterioscler Thromb Vasc Biol Date: 2020-03-05 Impact factor: 8.311
Authors: Michael S Garshick; Tessa J Barrett; Todd Wechter; Sarah Azarchi; Jose U Scher; Andrea Neimann; Stuart Katz; Judilyn Fuentes-Duculan; Maria V Cannizzaro; Sanja Jelic; Edward A Fisher; James G Krueger; Jeffrey S Berger Journal: Arterioscler Thromb Vasc Biol Date: 2019-04 Impact factor: 8.311
Authors: Marilyn T Wan; Drew A Torigian; Abass Alavi; Judith Alvarez; Zelma C Chiesa Fuxench; Megan H Noe; Maryte Papadopoulos; Daniel B Shin; Junko Takeshita; Thomas J Werner; Nehal N Mehta; Joel M Gelfand Journal: J Am Acad Dermatol Date: 2019-01-14 Impact factor: 11.527