Association of Apremilast With Vascular Inflammation and Cardiometabolic Function in Patients With Psoriasis: The VIP-A Phase 4, Open-label, Nonrandomized Clinical Trial.

Autor:	Gelfand JM; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia.; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia., Shin DB; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia., Armstrong AW; Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles., Tyring SK; Department of Dermatology, University of Texas Health Science Center at Houston, Houston., Blauvelt A; Oregon Medical Research Center, Portland., Gottlieb S; Dermatology and Skin Surgery Center, Exton, Pennsylvania., Lockshin BN; DermAssociates, Rockville, Maryland., Kalb RE; SUNY at Buffalo School of Medicine and Biomedical Sciences, Department of Dermatology, Buffalo Medical Group, Buffalo, New York., Fitzsimmons R; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia., Rodante J; Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland., Parel P; Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland., Manyak GA; Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland., Mendelsohn L; Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland., Noe MH; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Papadopoulos M; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia., Syed MN; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia., Werner TJ; Department of Radiology (Nuclear Medicine), Perelman School of Medicine, University of Pennsylvania, Philadelphia., Wan J; Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland., Playford MP; Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland., Alavi A; Department of Radiology (Nuclear Medicine), Perelman School of Medicine, University of Pennsylvania, Philadelphia., Mehta NN; Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Jazyk:	angličtina
Zdroj:	JAMA dermatology [JAMA Dermatol] 2022 Dec 01; Vol. 158 (12), pp. 1394-1403.
DOI:	10.1001/jamadermatol.2022.3862
Abstrakt:	Importance: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss. Objective: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition. Design, Setting, and Participants: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites in the United States. A total of 101 patients with moderate to severe psoriasis were screened, 70 enrolled, 60 completed week 16, and 39 completed week 52. Intervention: Apremilast, 30 mg, twice daily. Main Outcomes and Measures: Aortic vascular inflammation (measured by FDG-PET/CT), 68 cardiometabolic biomarkers, and abdominal fat composition (measured by CT) at week 16 and week 52 compared with baseline. Results: The mean (SD) age of the 70 patients was 47.5 (14.6) years, 54 were male (77.1%), 4 were Black (5.7%), and 58 were White (82.9%). There was no change in aortic vascular inflammation at week 16 (target to background ratio, -0.02; 95% CI, -0.08 to 0.05; P = .61) or week 52 (target to background ratio, -0.07; 95% CI, -0.15 to 0.01; P = .09) compared with baseline. At week 16, potentially beneficial decreases in interleukin 1b, valine, leucine, isoleucine, fetuin A, and branched-chain amino acids were observed. At week 52 compared with baseline, potentially beneficial decreases in ferritin, β-hydroxybutyrate, acetone, and ketone bodies, with an increase in apolipoprotein A-1, were observed, but there was a reduction in cholesterol efflux. There was an approximately 5% to 6% reduction in subcutaneous and visceral adiposity at week 16 that was maintained at week 52. Conclusions and Relevance: The findings of this nonrandomized clinical trial suggest that apremilast has a neutral association with aortic vascular inflammation, variable but generally beneficial associations with a subset of cardiometabolic biomarkers, and associations with reductions in visceral and subcutaneous fat, indicating that the drug may have an overall benefit for patients with cardiometabolic disease and psoriasis. Trial Registration: ClinicalTrials.gov Identifier: NCT03082729.
Databáze:	MEDLINE
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