Effects of the Tumor Necrosis Factor-α Antagonist Adalimumab on Arterial Inflammation Assessed by Positron Emission Tomography in Patients With Psoriasis

Abstract

P soriasis is a chronic immune-mediated disease affecting up to 3% of the population.1 Skin and joint inflammation are the hallmarks of psoriasis and an increase in the number of T lymphocytes, antigen presenting cells, macrophages, and neutrophils is found in psoriatic plaques. 2 The complex interplay between inflammatory cells and keratinocytes induces epidermal proliferation resulting in the typical indurated, scaly, and erythematous plaques of psoriasis.3 Psoriasis has been shown to increase the risk of myocardial infarction and stroke. [4][5][6][7] Psoriasis treatments include topical corticosteroids, vitamin D analogs and phototherapy and also systemic anti-inflammatory agents, such as methotrexate, cyclosporin, or biological agents targeting tumor necrosis factor-α (TNF-α) or interleukin (IL)-12/IL-23. 8 These systemic agents all have a profound effect on skin and joint inflammation. Clinical Perspective on p 90Atherosclerosis is also an inflammatory disease. 9 We hypothesized that treatment-induced reduction in the local inflammatory process in patients with psoriasis would be associated with decreased vascular inflammation as assessed by positron emission tomography/computed tomography (PET/CT). Methods Study Design and PatientsThis was an investigator-initiated, single-center, single-blind (cardiologist and all staff involved in vascular imaging and analysis were Background-Psoriasis is a chronic inflammatory disease associated with increased risks of myocardial infarction and stroke. Systemic treatments for moderate to severe psoriasis can reduce skin and joint inflammation; however, their effects on vascular inflammation are unknown. Methods and Results-This randomized, controlled trial included 30 patients with moderate to severe psoriasis and a history, or multiple risk factors, of coronary atherosclerosis. Patients were randomized (2:1) to receive either adalimumab subcutaneously for 4 months or to control nonsystemic treatment (topical therapies or phototherapy). Vascular inflammation was measured in the carotid artery and ascending aorta at baseline and week 15, by

Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

“…The average PASI 75 response rate in the placebo arm across all trials is 6.2%, whereas the average rate in studies of adult populations is 5.9% and in studies of children and young people is 11.1%. Three adult studies 106,108,132 have substantially higher placebo response rates (approximately 18-20%) than the other studies. Four studies, including the two trials in children and young people 72 and two in adults, 114,116 have approximately double the average placebo rate.…”

“…Table 41 showed that the PASI response rates in the placebo arms of the trials ranged from 0% 136 to 20%. 108 All of the trials varied by design, eligibility criteria, previous medication use, average age and other characteristics. All of these variations could contribute to differences in placebo response rates and, therefore, to differences in the relative efficacy of the intervention compared with placebo.…”

Psoríase e Doença Cardiovascular: Impacto da Terapêutica com Inibidores do TNF-alfa

“…44 Os doentes foram randomizados (2:1) em dois grupos, o grupo tratado com adalimumab e o grupo controlo (doentes tratados com agentes tópicos, fototerapia ou sem tratamento), e seguidos durante 16 semanas. A inflamação vascular foi avaliada em dois momentos distintos: 10 dias antes do início da terapêutica com adalimumab e à 15ª semana de tratamento, nas artérias carótidas e aorta ascendente, com recurso a imagens obtidas por 18FDG-PET/ CT. Os resultados foram mensurados pela determinação da média dos valores máximos de TBR (MeanMaxTBR), pela média dos valores médios de TBR (MeanMeanTBR) e pelo valor de TBR no segmento mais doente, obtidos quer no vaso com maior valor basal de TBR, quer nas artérias carótidas e aorta ascendente separadamente.…”

Assessment of atherosclerosis in large vessel walls: A comprehensive review of FDG-PET/CT image acquisition protocols and methods for uptake quantification

“…Using this method, investigators could compare the vessels which are more diseased and may better show the effect of interventions. 14,18,59 Superiority of the methods using vessel with the highest baseline FDG uptake activity (index vessel) over other methods evaluating similar anatomical vessels (carotid vs carotid or aorta vs aorta) for evaluation and comparison between groups is not clear. In the studies showing that the same vessels have significantly different FDG uptake between groups, index vessel may or may not be able to show this difference.…”

“…3,14-17 These methodologies may lead to different image qualities and inconsistent final findings. [18][19][20] Herein, we show the different patient preparation and image acquisition protocols and describe their influences on image quality and final findings. Also, we summarize common measurement indices and quantification methods and discuss their strengths and weaknesses.…”