Alvaro González-Cantero1, Daniel Ortega-Quijano1, Noelia Álvarez-Díaz2, Maria Asuncion Ballester1, Natalia Jimenez-Gomez1, Pedro Jaen1, Jorge González-Cantero3, Jorge Luis González-Calvin4, Maria G Barderas5, Daniel B Shin6, Nehal N Mehta7, Joel M Gelfand8. 1. Department of Dermatology, Hospital Universitario Ramon y Cajal, Madrid, Spain. 2. Medical Library, Hospital Universitario Ramón y Cajal, Madrid, Spain. 3. Department of Radiology, University General Hospital Gregorio Marañón, Madrid, Spain. 4. Department of Gastroenterology, University Hospital San Cecilio, Granada, Spain. 5. Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain. 6. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 7. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. 8. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: Joel.Gelfand@pennmedicine.upenn.edu.
Abstract
BACKGROUND: The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use. OBJECTIVE: The objective of this study was to examine the impact of licensed biological therapies on imaging and biomarkers of cardiovascular disease risk in patients with psoriasis by a systematic review and meta-analysis of placebo-controlled trials. METHODS: A comprehensive search of studies published before 1 June 2020 was performed in Medline-Ovid, EMBASE, and CENTRAL using a predefined strategy to identify relevant articles. RESULTS: Five studies were included for the final examination, and two studies were included in the meta-analysis. We did not find a significant reduction in aortic vascular inflammation in patients treated with adalimumab compared with those who received placebo at weeks 12-16. There was no beneficial effect on imaging biomarkers (aortic vascular inflammation or flow-mediated dilatation) of cardiovascular disease risk in patients exposed to biological therapies (adalimumab and secukinumab) compared with those exposed to placebo, except for ustekinumab showing a reduction in aortic vascular inflammation at week 12 but not at week 52 after the open-label extension period. The strongest reduction in blood-based cardiometabolic risk biomarkers was observed with adalimumab (CRP, TNF-α, IL-6, and GlycA) and phototherapy (CRP and IL-6) compared with that observed with placebo. CONCLUSIONS: Randomized controlled trials show that ustekinumab reduces aortic vascular inflammation and that TNF-α inhibitors and phototherapy reduce CRP and IL-6. These surrogate marker findings require randomized controlled trials evaluating cardiovascular events to inform clinical practice.
BACKGROUND: The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use. OBJECTIVE: The objective of this study was to examine the impact of licensed biological therapies on imaging and biomarkers of cardiovascular disease risk in patients with psoriasis by a systematic review and meta-analysis of placebo-controlled trials. METHODS: A comprehensive search of studies published before 1 June 2020 was performed in Medline-Ovid, EMBASE, and CENTRAL using a predefined strategy to identify relevant articles. RESULTS: Five studies were included for the final examination, and two studies were included in the meta-analysis. We did not find a significant reduction in aortic vascular inflammation in patients treated with adalimumab compared with those who received placebo at weeks 12-16. There was no beneficial effect on imaging biomarkers (aortic vascular inflammation or flow-mediated dilatation) of cardiovascular disease risk in patients exposed to biological therapies (adalimumab and secukinumab) compared with those exposed to placebo, except for ustekinumab showing a reduction in aortic vascular inflammation at week 12 but not at week 52 after the open-label extension period. The strongest reduction in blood-based cardiometabolic risk biomarkers was observed with adalimumab (CRP, TNF-α, IL-6, and GlycA) and phototherapy (CRP and IL-6) compared with that observed with placebo. CONCLUSIONS: Randomized controlled trials show that ustekinumab reduces aortic vascular inflammation and that TNF-α inhibitors and phototherapy reduce CRP and IL-6. These surrogate marker findings require randomized controlled trials evaluating cardiovascular events to inform clinical practice.
Authors: Joel M Gelfand; Daniel B Shin; April W Armstrong; Stephen K Tyring; Andrew Blauvelt; Scott Gottlieb; Benjamin N Lockshin; Robert E Kalb; Robert Fitzsimmons; Justin Rodante; Philip Parel; Grigory A Manyak; Laurel Mendelsohn; Megan H Noe; Maryte Papadopoulos; Maha N Syed; Thomas J Werner; Joy Wan; Martin P Playford; Abass Alavi; Nehal N Mehta Journal: JAMA Dermatol Date: 2022-09-21 Impact factor: 11.816