The use of biologic therapy has increased over the past decade well beyond primary autoimmune diseases. Indeed, a recent trial using an anti-IL-1beta antibody reduced second myocardial infarction (MI) in those who have had MI. Psoriasis is a chronic inflammatory disease often treated with biologics when severe, is associated with increased risk of MI, in part driven by high-risk coronary plaque phenotypes by coronary computed tomography angiography (CCTA). We hypothesized that we would observe a reduction in inflammatory-driven phenotypes of coronary plaque, including non-calcified coronary plaque burden and lipid-rich necrotic core in those treated with biologic therapy after one-year compared with non-biologic therapy.

Background Psoriasis, a chronic inflammatory disease associated with an accelerated risk of MI, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease (CAD) burden composed of non-calcified plaques with high-risk features. However, inadequate efforts have been made to directly measure CAD in this vulnerable population. As such, we sought to compare total (TB) and non-calcified (NCB) coronary plaque burden, and high-risk plaque (HRP) prevalence, between psoriasis patients (n=105), hyperlipidemic patients eligible for statin therapy under NCEP-ATP III guidelines (n=100) who were ~10 years older, and non-psoriasis healthy volunteers (HV) (n=25). Methods Patients underwent coronary computed-tomography angiography (CCTA) for TB and NCB quantification, and HRP identification, defined as low-attenuation (<30 HU), positive remodeling (>1.10), and spotty calcification. A consecutive sample of the first 50 psoriasis patients were scanned again at 1 year following therapy. Results Despite being younger and at lower traditional risk than hyperlipidemic patients, psoriasis patients had increased NCB (mean±S.D.:1.18±0.33 vs 1.11±0.32, p=0.02), and similar HRP prevalence (p=0.58). Furthermore, compared to HV, psoriasis patients had increased TB (1.22±0.31 vs 1.04±0.22, p=0.001), NCB (1.18±0.33 vs 1.03±0.21, p=0.004), and HRP prevalence beyond traditional risk (OR=6.0, 95% CI: 1.1–31.7; p=0.03). Finally, amongst psoriasis patients followed for 1-year, improvement in psoriasis severity associated with improvement in TB (β=0.45, 0.23–0.67; p<0.001) and NCB (β=0.53, 0.32–0.74; p<0.001) beyond traditional risk factors. Conclusions Psoriasis patients had greater NCB and increased HRP prevalence than HV. Additionally, psoriasis patients had elevated NCB and equivalent HRP prevalence as older, hyperlipidemic patients. Finally, modulation of target organ inflammation (eg. skin) associated with an improvement in NCB at 1 year, suggesting that control of remote sites of inflammation may translate into reduced CAD risk.

IMPORTANCE Psoriasis is a chronic inflammatory skin disease associated with increased coronary plaque burden and cardiovascular events. Biologic therapy for psoriasis has been found to be favorably associated with luminal coronary plaque, but it is unclear whether these associations are attributable to direct anti-inflammatory effects on the coronary arteries. OBJECTIVE To investigate the association of biologic therapy with coronary inflammation in patients with psoriasis using the perivascular fat attenuation index (FAI), a novel imaging biomarker that assesses coronary inflammation by mapping spatial changes of perivascular fat composition via coronary computed tomography angiography (CCTA). DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study performed from January 1, 2013, through March 31, 2019, analyzed changes in FAI in patients with moderate to severe psoriasis who underwent CCTA at baseline and at 1 year and were not receiving biologic psoriasis therapy at baseline. EXPOSURES Biologic therapy for psoriasis. MAIN OUTCOMES AND MEASURES Perivascular FAI mapping was performed based on an established method by a reader blinded to patient demographics, visit, and treatment status. RESULTS Of the 134 patients (mean [SD] age, 51.1 [12.1] years; 84 [62.5%] male), most had low cardiovascular risk by traditional risk scores (median 10-year Framingham Risk Score, 3% [interquartile range, 1%-7%]) and moderate to severe skin disease. Of these patients, 82 received biologic psoriasis therapy (anti-tumor necrosis factor α, anti-interleukin [IL] 12/23, or anti-IL-17) for 1 year, and 52 did not receive any biologic therapy and were given topical or light therapy (control group). At baseline, 46 patients (27 in the treated group and 19 in the untreated group) had a focal coronary atherosclerotic plaque. Biologic therapy was associated with a significant decrease in FAI at 1 year (median FAI −71.22 HU [interquartile range (IQR), −75.85 to −68.

Switching bDMARD therapies is a recommended strategy for patients who experience treatment failure. Many factors must be considered for determining which agent to switch to including PsA disease characteristics, comorbidities, cardiometabolic risk factors, treatment history, and patient preference. Switching between TNFis can be effective for many patients, but bDMARDs with different mechanisms of action may be superior alternatives.

To compare drug survival of ixekizumab to other IL-17 inhibitors (IL-17i) and TNF inhibitors (TNFi) among patients with psoriasis (PsO) in a real-world setting. Participants included adult PsO patients enrolled in the Corrona Psoriasis Registry who initiated ixekizumab, TNFi, or other IL-17i between 16 March 2016 to 10 August 2019 and completed ≥1 follow-up visit. Multivariable adjusted hazard ratios (HR) were calculated to estimate the risk for drug discontinuation in the ixekizumab group relative to the other drugs. Among the 1604 drug initiations, 552 initiated ixekizumab, 450 initiated TNFi, and 602 initiated other IL-17i. Mean age was 51 years, 49% were women, and 52% were obese (BMI > 30). Ixekizumab patients had a higher proportion of patients with PASI >12 at drug initiation (24%) than TNFi (15%) and other IL-17i (19%). Over a median of 11 months of follow-up, 723/1604 (45%) drug discontinuations occurred. Persistence of ixekizumab, TNFi, and other IL-17i at 24-months were 68%, 33%, and 46%, among biologic-naïve patients (n = 543), and 46%, 23%, and 36%, for biologic-experienced patients (n = 1061), respectively. Ixekizumab patients had a 64% lower risk of discontinuation vs TNFi (HR = 0.36; 95% CI 0.27-0.47) and a 31% lower risk vs other IL-17i (HR = 0.69, 95% CI 0.55-0.87) after adjustment for biologic experience and other covariates. HRs were similar when limited to patients with moderate-to-severe PsO (BSA > 3, PASI > 3, and IGA > 1, n = 1076) at initiation. In our study of real-world patients with PsO, initiators of ixekizumab had more prolonged drug survival than both initiators of TNFi and other IL-17i up to 2 years of follow-up.

No abstract

BACKGROUND. Psoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis. METHODS. Consecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50). RESULTS. Patients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc 3 vs. 13370.7 ± 806.8 cc 3 , P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm 2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm 2 vs. 0.91 ± 0.2 mm 2 , P < 0.001). VAT associated with NCB in fully adjusted models (β = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc 3 to 15,158.7 ± 881.5 cc 3 ; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc 3 to 16310.4 ± 889.6 cc 3 ; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (β = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (β = 0.39, P = 0.003). CONCLUSIONS. Inflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis. TRIAL REGISTRATION. ClinicalTrials.gov NCT01778569.

BackgroundInformation on the factors that influence treatment management decisions for psoriatic arthritis (PsA) is limited.ObjectiveOur objective was to evaluate the impact of clinical specialty setting and geographic region on the management of patients with PsA in the USA.MethodsLOOP was a multicenter, cross-sectional, observational study conducted across 44 sites in the USA. Patients were aged ≥ 18 years with a suspected or established diagnosis of PsA and were routinely visiting a rheumatologist or dermatologist. All patients enrolled in the study were assessed by both a rheumatologist and a dermatologist. Primary outcomes were the times from symptom onset to PsA diagnosis; PsA diagnosis to first conventional synthetic disease-modifying antirheumatic drug (csDMARD); PsA diagnosis to first biologic DMARD (bDMARD); and first csDMARD to first bDMARD.ResultsOf 681 patients enrolled in the study, 513 had a confirmed diagnosis of PsA and were included in this analysis. More patients were recruited by rheumatologists (71.3%) than by dermatologists (28.7%). The median time from symptom onset to diagnosis of PsA was significantly shorter for patients enrolled by rheumatologists than for those enrolled by dermatologists (1.0 vs. 2.6 years; p < 0.001). Disease activity and burden were generally similar across enrolling specialties. However, patients in western areas of the USA had less severe disease than those in central or eastern areas, including measures of joint involvement, enthesitis, and dactylitis.ConclusionsThere was a substantial delay in the time from symptom onset to diagnosis in this study population, and this was significantly longer for patients enrolled in the dermatology versus the rheumatology setting. This supports the need for collaboration across specialties to ensure faster recognition and treatment of PsA.Electronic supplementary materialThe online version of this article (10.1007/s40257-019-00470-6) contains supplementary material, which is available to authorized users.