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

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, ß-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.

Treatment of Plaque Psoriasis With an Excimer Laser Utilizing an Optimal Therapeutic UVB Dose Protocol.

Background: Traditionally, treatment with the excimer laser requires determining the minimal erythema dose on healthy skin or using plaque-based induration; however, these protocols often lead to underdosing of psoriatic plaques and reduced treatment efficacy. Objective: To prospectively evaluate the effect of the excimer laser on plaque psoriasis using an optimal therapeutic dose (OTD) protocol. Methods: Subjects with stable plaque psoriasis were tested with the Multi-Microdose (MMD) tip on the XTRAC excimer laser to determine a minimum blistering dose (MBD). Treatment was then initiated at 20% less than the MBD. A single psoriatic lesion was treated once weekly for up to 11 sessions. The change from baseline of the target lesion's modified psoriasis area severity index (mPASI), quality of life and safety were evaluated. Results: Thirteen subjects with a mean age of 48.9±14.9 years and Fitzpatrick skin types I-IV participated in the study. Target plaque mPASI significantly decreased at all time points relative to baseline with significant improvement by the second treatment. Patients reached mPASI-75 within 5±2 sessions. By the end of the study 92% of patients achieved mPASI-75. On average, patients maintained an mPASI score ≥50% for 60 days. Treatment was well tolerated with no erosions or hyperpigmentation. Erythema was the most common adverse event. Conclusion: The OTDTM protocol with the MMD® tip allows determining the optimal dose locally on the psoriatic plaque itself. Consequently, ineffectual dosing levels and treatments are minimized. The OTD protocol reduces treatment frequency from 2-3 times per week to once weekly. J Drugs Dermatol. 2020;19(4):349-354. doi:10.36849/JDD.2020.4891.

A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S).

Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose-positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was -0.053 (95% confidence interval = -0.169 to 0.064; P= 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P= 0.0063) and ferritin (P= 0.0354), and an increase in fetuin-A (P= 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.

Visceral Adiposity in Psoriasis is Associated With Vascular Inflammation by 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Beyond Cardiometabolic Disease Risk Factors in an Observational Cohort Study.

OBJECTIVES: The authors sought to examine the relationship between visceral adipose tissue (VAT) and vascular inflammation (VI) by 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in psoriasis (PSO). Furthermore, we evaluated whether treatment of PSO modulated VAT and VI. BACKGROUND: PSO, a chronic inflammatory skin disease, is associated with VI by 18F-FDG PET/CT and increased cardiometabolic risk including adipose tissue dysregulation. Recently, VI was associated with future cardiovascular events; however, the relationship of visceral and subcutaneous adiposity with VI in PSO has yet to be evaluated. METHODS: Consecutive PSO patients (N = 77) underwent 18F-FDG PET/CT scans to measure VI and abdominal adiposity. A subset of PSO patients with severe skin disease was scanned at 1 year following PSO treatment (N = 13). RESULTS: The cohort was middle aged (51.8 ± 12.6 years), predominantly male (n = 44, 57%), had low cardiovascular risk by Framingham 10-year risk (median 4 years [interquartile range (IQR): 2 to 7 years]), and mild-to-moderate skin disease (5.2 [IQR: 3.0 to 8.5]). PSO disease severity associated with VAT (ß = 0.33; p = 0.004) beyond SAT (ß = 0.30; p = 0.005). VAT (ß = 0.55; p < 0.001), but not SAT (ß = 0.15; p = 0.11), associated with VI beyond cardiovascular risk factors. We followed a subset of severe PSO patients treated aggressively for PSO and observed improvement in PSO severity and VAT, which was associated with an improvement in VI at 1 year beyond cardiovascular risk factors (ß = 0.53; p = 0.049). CONCLUSIONS: Volume-based CT measurement of VAT may capture metabolic risk associated with VI compared to subcutaneous adipose tissue in PSO. PSO treatment associated with a decrease in VAT as well as decrease in VI suggesting VAT as a relevant biomarker related to VI in PSO.

Association Between Skin and Aortic Vascular Inflammation in Patients With Psoriasis: A Case-Cohort Study Using Positron Emission Tomography/Computed Tomography.

Importance: Inflammation is critical in the development of atherosclerosis. Psoriasis is a chronic inflammatory skin disease that is associated with increased vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography in vivo and future cardiovascular events. It provides a human model to understand the effect of treating inflammation in a target organ (eg, the skin) on vascular diseases. Objective: To investigate the association between change in skin disease severity and change in vascular inflammation at 1 year and to characterize the impact of 1 year of anti-tumor necrosis factor therapy on vascular inflammation. Design, Setting, and Participants: In this prospective cohort study, 220 participants from outpatient practices were recruited at the US National Institutes of Health. A total of 115 consecutively recruited patients with psoriasis were followed up at 1 year. The study was conducted from January 1, 2013, through October 31, 2016, with data analyzed in November 2016. Exposure: Skin inflammation measured as Psoriasis Area and Severity Index (PASI) score. Main Outcomes and Measures: Vascular inflammation assessed as target-to-background ratio by 18fluorodeoxyglucose positron emission tomography/computed tomography. Results: Among the 115 patients, the mean (SD) age at 1-year follow-up was 50.8 (12.8) years and 68 were men (59%). The cohort had a low cardiovascular risk by Framingham risk score and mild-to-moderate psoriasis, with a median PASI score of 5.2 (interquartile range, 3.0-8.9). At follow-up, the total cohort had a median improvement in PASI score of 33%, with use of topical therapy (60%), biological therapy (66%, mostly anti-tumor necrosis factor) and phototherapy (15%) (P < .001). Moreover, improvement in PASI score was associated with improvement in target-to-background ratio of 6%, mainly driven by those with higher responses in PASI score (P < .001). This association persisted beyond traditional risk factors (ß = 0.19; 95% CI, 0.012-0.375; P = .03) and was the strongest in those initiated with anti-tumor necrosis factor therapy (ß = 0.79; 95% CI, 0.269-1.311; P = .03). Conclusions and Relevance: Improvement in psoriasis skin disease severity was associated with improvement in aortic vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography, with greater improvement in aortic vascular inflammation observed in those who had higher than 75% reduction in skin disease severity. These findings suggest that controlling remote target organ inflammation (eg, in the skin) may improve vascular diseases; however, randomized clinical trials are needed to confirm these findings.

GlycA Is a Novel Biomarker of Inflammation and Subclinical Cardiovascular Disease in Psoriasis.

RATIONALE: GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein in psoriasis is unknown. OBJECTIVE: To investigate the relationships between GlycA and psoriasis and between GlycA and subclinical CVD. METHODS AND RESULTS: Patients with psoriasis and controls (n=412) participated in a 2-stage study. We measured GlycA by nuclear magnetic resonance spectroscopy. National Institutes of Health (NIH) participants underwent 18-F Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18-FDG PET/CT) scans to assess vascular inflammation (VI) and coronary computed tomographic angiography to quantify coronary artery disease burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. high-sensitivity C-reactive protein and GlycA were increased in psoriasis compared with controls (GlycA: [PENN: 408.8±75.4 versus 289.4±60.2, P<0.0001; NIH: 415.8±63.2 versus 346.2±46, P<0.0001]) and demonstrated a dose-response with psoriasis severity. In stage 2, VI (ß=0.36, P<0.001) and coronary artery disease (ß=0.29, P=0.004) associated with GlycA beyond CV risk factors in psoriasis. In receiver operating characteristic analysis, GlycA added value in predicting VI (P=0.01) and coronary artery disease (P<0.01). Finally, initiating anti-tumor necrosis factor therapy (n=16) reduced psoriasis severity (P<0.001), GlycA (463.7±92.5 versus 370.1±78.5, P<0.001) and VI (1.93±0.36 versus 1.76±0.19, P<0.001), whereas GlycA remained associated with VI (ß=0.56, P<0.001) post treatment. CONCLUSIONS: GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and high-sensitivity C-reactive protein. Moreover, psoriasis treatment reduced GlycA and VI. These findings support the potential use of GlycA in subclinical CVD risk assessment in psoriasis and potentially other inflammatory diseases.

Self-reported depression in psoriasis is associated with subclinical vascular diseases.

BACKGROUND AND AIMS: Psoriasis is a chronic inflammatory disorder associated with vascular inflammation, measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), and an increased risk of myocardial infarction. Patients with psoriasis are also more likely to suffer from comorbid depression. Whether depression accelerates the development of subclinical atherosclerosis in psoriasis is unknown. METHODS: Patients were selected from within a larger psoriasis cohort. Those who reported a history of depression (N = 36) on survey were matched by age and gender to patients who reported no history of psychiatric illness (N = 36). Target-to-background ratio from FDG PET/CT was used to assess aortic vascular inflammation and coronary CT angiography scans were analyzed to determine coronary plaque burden. Multivariable linear regression was performed to understand the effect of self-reported depression on vascular inflammation and coronary plaque burden after adjustment for Framingham risk (standardized ß reported). RESULTS: In unadjusted analyses, vascular inflammation and coronary plaque burden were significantly increased in patients with self-reported depression as compared to patients with psoriasis alone. After adjustment for Framingham Risk Score, vascular inflammation (ß = 0.26, p = 0.02), total plaque burden (ß = 0.17, p = 0.03), and non-calcified burden (ß = 0.17, p = 0.03) were associated with self-reported depression. CONCLUSIONS: Self-reported depression in psoriasis is associated with increased vascular inflammation and coronary plaque burden. Depression may play an important role in promoting subclinical atherosclerosis beyond traditional cardiovascular risk factors.

Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study.

OBJECTIVE: To understand whether directly measured psoriasis severity is associated with vascular inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography computed tomography. APPROACH: In-depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index. Vascular inflammation was measured using average aortic target-to-background ratio using (18)F-fluorodeoxyglucose positron emission tomography computed tomography. RESULTS: Both the psoriasis patients (28 men and 32 women, mean age 47 years) and controls (13 men and 7 women, mean age 41 years) were young with low cardiovascular risk. Psoriasis area severity index scores (median 5.4; interquartile range 2.8-8.3) were consistent with mild-to-moderate skin disease severity. Increasing psoriasis area severity index score was associated with an increase in aortic target-to-background ratio (ß=0.41, P=0.001), an association that changed little after adjustment for age, sex, and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis, 3.7±1.2 versus 2.9±1.2; P=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 versus 195.4±157.8 ng/mL; P<0.01) and neutrophil elastase-1 (43.0±2.4 versus 30.8±6.7 ng/mL; P<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein was related to both psoriasis skin disease severity (ß=0.53; P=0.02) and vascular inflammation (ß=0.48; P=0.02). CONCLUSIONS: Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 was related to both skin disease severity and vascular inflammation.

Dermatologic side effects of psychotropic medications.

BACKGROUND: Although relatively uncommon, cutaneous reactions to psychotropic medications may thwart treatment of psychiatric illness and confuse diagnostic efforts especially when they occur in the context of comorbid medical conditions. Psychiatrists may be asked to comment on whether a particular cutaneous condition is due to a psychotropic medication or to recommend a replacement psychotropic agent. OBJECTIVE: To review the available literature describing cutaneous adverse effects prompted by psychotropic medications. METHOD: A search of the literature using PubMed was undertaken using the terms "psychotropic," "psychiatric," "antidepressant," "anxiolytic," "mood stabilizer," "antipsychotic," and "neuroleptic" in combination with either of the terms "dermatologic," "cutaneous" or "skin." RESULTS: Psychotropic medications from all classes have been associated with a broad variety of dermatologic reactions with variable rates of incidence. Psychiatrists should be aware of the potential cutaneous adverse effects of the medications they prescribe. Psychiatrists practicing in the general hospital, where cutaneous symptoms may present for any number of reasons, should be aware of the typical presentations and relative likelihood of these reactions to forestall unnecessary "blaming" of psychotropics for cutaneous reactions.