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

This is the author accepted manuscript. The final version is available from the American Heart Association via http://dx.doi.org/10.1161/ATVBAHA.115.306460OBJECTIVE: 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 (β=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 (β=0.53; P=0.02) and vascular inflammation (β=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.JMT is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z) and the NIHR Cambridge Biomedical Research Centre. JHFR is part-supported by the HEFCE, the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trus

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Impact of Clinical Specialty Setting and Geographic Regions on Disease Management in Patients with Psoriatic Arthritis in the United States: A Multicenter Observational Study.

BACKGROUND: Information on the factors that influence treatment management decisions for psoriatic arthritis (PsA) is limited. OBJECTIVE: Our objective was to evaluate the impact of clinical specialty setting and geographic region on the management of patients with PsA in the USA. METHODS: LOOP 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. RESULTS: Of 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 \u3c 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. CONCLUSIONS: There 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

Efficacy, safety, usability, and acceptability of risankizumab 150 mg formulation administered by prefilled syringe or by an autoinjector for moderate to severe plaque psoriasis

Background Risankizumab is approved for treatment of moderate to severe plaque psoriasis. Availability of a patient-controlled single self-injection of risankizumab may improve adherence and long-term management of psoriasis. Objective To investigate efficacy, safety, and usability of a new risankizumab 150 mg/mL formulation administered as a single subcutaneous injection via prefilled syringe (PFS) or autoinjector (AI). Methods Efficacy, safety, usability, and acceptability of risankizumab 150 mg/mL PFS or AI were investigated in adults with moderate to severe psoriasis in two phase 3 studies. Study 1 was a multicenter, randomized, double-blinded, placebo-controlled study that investigated 150 mg/mL risankizumab PFS; study 2 was a multicenter, single-arm, open-label study that investigated 150 mg/mL risankizumab AI. Results At week 16, risankizumab 150 mg/mL demonstrated efficacy vs. placebo (Psoriasis Area and Severity Index ≥90% improvement (PASI 90), 62.9% vs. 3.8%; static Physician Global Assessment (sPGA) 0/1, 78.1% vs. 9.6%; both p< .001) in study 1; in study 2, PASI 90 and sPGA 0/1 were 66.7%, and 81.5%, respectively. All patients successfully self-administered study treatments via PFS or AI. Acceptability of self-injection was high in both studies. Efficacy and safety of risankizumab 150 mg/mL were comparable with results from previous risankizumab phase 3 studies using the 90 mg/mL formulation. Conclusions The efficacy, safety, and usability of 150 mg/mL risankizumab delivered as a single PFS or AI injection support use of this new formulation in patients with moderate to severe plaque psoriasis. Clinical trials NCT03875482 and NCT038750

Examining disease severity and symptom improvement with patient and physician assessments: Results from a phase IV analysis of apremilast in patients with moderate plaque psoriasis

Background: UNVEIL is the first study of apremilast in patients (pts) with moderate psoriasis (body surface area [BSA] 5%-10%) naive to biologic and systemic therapy. Physician and pt evaluations help determine treatment effectiveness. Improvements on physician and pt assessments over 52 wks are described. Methods: Patients with chronic moderate plaque psoriasis (BSA 5%-10%; Static Physician’s Global Assessment [sPGA] score 3 [0-5 scale]) were randomized (2:1) to apremilast 30 mg bid (APR) or placebo (PBO) for 16 wks. Pts continued APR (APR/APR) or switched from PBO to APR (PBO/APR) through wk 52 (open-label treatment phase). Physician assessments were the product of sPGA and BSA (PGA×BSA), proportion of pts who achieved sPGA response (score of 0 [clear] or 1 [almost clear]), and PGA×BSA-75 response (≥75% improvement from baseline [BL]). Pt assessments were Dermatology Life Quality Index (DLQI), pruritus VAS (0-100 mm), Treatment Satisfaction Questionnaire for Medication (TSQM), and Pt’s Global Assessment (PtGA [0-4 scale]). Results: In randomized pts (PBO n = 73; APR n = 148), mean BL BSA was 7.2%, PGA×BSA was 21.8DLQI was 11.0, and pruritus VAS was 56.6 mm. At wk 16, APR showed greater mean improvement in PGA×BSA vs. PBO (−48.1% vs. −10.2%; P \u3c .0001), and more pts achieved sPGA response and PGA×BSA-75 with APR vs. PBO (30.4% vs. 9.6% and 35.1% vs. 12.3%, respectively). Achievement of DLQI response (≥5-point decrease from BL in pts with BL DLQI \u3e5) was greater with APR at wk 16 vs. PBO (63.8% vs. 34.5%), as was pruritus VAS response (improvement ≥20%: 62.8% vs. 45.2%) and TSQM global satisfaction (63.2 vs. 48.7) and effectiveness (57.3 vs. 38.8). PtGA ≤1 was achieved by more pts receiving APR vs. PBO (33.8% vs. 20.5%). At wk 52, changes in PGA×BSA were −42.2% (PBO/APR) and −55.5% (APR/APR); 45.3% (PBO/APR) and 42.1% (APR/APR) of pts achieved PGA×BSA-75, 35.9% (PBO/APR) and 33.1% (APR/APR) achieved sPGA response, 55.6% (PBO/APR) and 59.4% (APR/APR) achieved DLQI response, and 68.8% (PBO/APR) and 66.9% (APR/APR) achieved pruritus VAS response. TSQM global satisfaction (PBO/APR 59.2; APR/APR 59.9) and effectiveness (PBO/APR 57.7; APR/APR 54.1) scores were similar between treatment groups at wk 52; 42.2% (PBO/APR) vs. 37.2% (APR/APR) had PtGA ≤1. No new safety/tolerability issues emerged. Conclusion: Physician and pt assessments showed improvement with APR up to 52 wks in biologic- and systemic-naive pts with moderate psoriasis (BSA 5%-10%)

The Efficacy and Safety of Bimekizumab for Plaque Psoriasis: An Expert Consensus Panel

Abstract Introduction Psoriasis is a chronic inflammatory condition affecting the skin, joints, and several other organ systems with significant disease burden. Bimekizumab is the first monoclonal antibody targeting both interleukin (IL)-17A and interleukin-17F and has demonstrated efficacy for treating moderate to severe psoriasis. Limited guidelines exist for incorporating this drug into clinical practice. The purpose of this study was for a panel of experts in psoriasis management to synthesize current literature and provide consensus statements with guidance on use of bimekizumab. Methods A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the use of bimekizumab for moderate to severe psoriasis and psoriatic arthritis. A panel of nine dermatologists with significant expertise in treatment of psoriasis gathered to review the articles and create consensus statements on this new medication. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using Strength of Recommendation Taxonomy criteria. Results The literature search produced 102 articles that met criteria. A thorough screening of the studies for relevance to the research question resulted in 19 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 14 consensus statements and recommendations, 12 of which were given a strength of “A”, one of which was given a strength of “B”, and one of which was given a strength of “C”. Conclusion Bimekizumab results in rapid and long-lasting clinical improvement for patients with moderate to severe plaque psoriasis and psoriatic arthritis. It has demonstrated superior efficacy when compared to several other biologics. The safety profile is consistent with other biologics, except for an increased incidence of oropharyngeal candidiasis