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

ABSTRACT: 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.

SUBMITTER: Gelfand JM

PROVIDER: S-EPMC7434644 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Gelfand Joel M JM Shin Daniel B DB Duffin Kristina Callis KC Armstrong April W AW Blauvelt Andrew A Tyring Stephen K SK Menter Alan A Gottlieb Scott S Lockshin Benjamin N BN Simpson Eric L EL Kianifard Farid F Sarkar Rajendra Prasad RP Muscianisi Elisa E Steadman Jennifer J Ahlman Mark A MA Playford Martin P MP Joshi Aditya A AA Dey Amit K AK Werner Thomas J TJ Alavi Abass A Mehta Nehal N NN

The Journal of investigative dermatology 20200221 9

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 <sup>18</sup>F-2-fluorodeoxyglu ...[more]

PMID: 32088207

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Project description:TitleSecukinumab efficacy and safety in Indian patients with moderate-to-severe plaque psoriasis: sub-analysis from FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), a randomized, placebo-controlled, phase 3 study.BackgroundEvidence has suggested Interleukin (IL)-17A to be an important effector cytokine in the pathogenesis of psoriasis. Here, we report results for an Indian sub-population from a multinational study FIXTURE, designed to assess the safety, tolerability, and long-term efficacy of fully human anti-IL-17A monoclonal antibody secukinumab in patients with moderate-to-severe plaque psoriasis.Materials and methodsIn this double-dummy, placebo controlled, 52-weeks phase 3 study FIXTURE, 149 Indian patients were randomized 1:1:1:1 to receive secukinumab at a dose of 300 mg or 150 mg, etanercept, or placebo. The study objective was to show the superiority of secukinumab over placebo at week 12, vis-à-vis proportion of patients achieving a reduction of 75% or more from the baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (IGA mod 2011) (co-primary end points).ResultsAt week 12, 61.0% and 55.9% patients in secukinumab 300 mg and 150 mg groups, respectively, achieved PASI 75 response compared to 20.0% in the etanercept and 7.1% in the placebo groups. Similarly, IGA mod 2011 0 or 1 response was achieved by 43.9% and 20.6% in patients in the secukinumab 300 mg and 150 mg group, respectively, vs. 13.3% in the etanercept and 2.4% in the placebo groups at week 12. Likewise, higher proportions of patients in secukinumab 300 mg (41.5%) and 150 mg (20.6%) group were PASI 90 responders at week 12 than those in the etanercept (10.0%) or placebo (0.0%) groups. The incidences of adverse events (AEs), during the induction period were similar in all the treatment groups. Overall secukinumab was well-tolerated at both doses in the Indian sub-population.ConclusionThe results from the Indian sub-population suggest that secukinumab is an efficacious and safe drug for use in moderate-to-severe chronic plaque psoriasis.

Project description:ImportanceInflammation is critical to atherosclerosis. Psoriasis, a chronic inflammatory disease associated with early cardiovascular events and increased aortic vascular inflammation (VI), provides a model to study the process of early atherogenesis. Fludeoxyglucose F 18 positron emission tomography/computed tomography (18F-FDG PET/CT) helps quantify aortic VI, and coronary computed tomography angiography provides coronary artery disease (CAD) assessment through evaluation of total plaque burden (TB) and noncalcified coronary plaque burden (NCB), luminal stenosis, and high-risk plaques (HRP). To our knowledge, association between aortic VI and broad CAD indices has not yet been assessed in a chronic inflammatory disease state. Such a study may provide information regarding the utility of aortic VI in capturing early CAD.ObjectiveTo assess the association between aortic VI and CAD indices, including TB, NCB, luminal stenosis, and HRP prevalence, in psoriasis.Design, setting, and participantsIn a cross-sectional cohort study at the National Institutes of Health, 215 consecutive patients with psoriasis were recruited from surrounding outpatient dermatology practices. All patients underwent 18F-FDG PET/CT for aortic VI assessment, and 190 of 215 patients underwent coronary computed tomography angiography to characterize CAD. The study was conducted between January 1, 2013, and May 31, 2017. Data were analyzed in March 2018.ExposuresAortic VI assessed by 18F-FDG PET/CT.Main outcomes and measuresPrimary outcome: TB and NCB. Secondary outcomes: luminal stenosis and HRP.ResultsAmong 215 patients with psoriasis (mean [SD] age, 50.4 [12.6] years; 126 men [59%]), patients with increased aortic VI had increased TB (standardized β = 0.48; P < .001), and higher prevalence of luminal stenosis (OR, 3.63; 95% CI, 1.71-7.70; P = .001) and HRP (OR, 3.05; 95% CI, 1.42-6.47; P = .004). The aortic VI and TB association was primarily driven by NCB (β = 0.49; P < .001), whereas the aortic VI and HRP association was driven by low-attenuation plaque (OR, 5.63; 95% CI, 1.96-16.19; P = .001). All associations of aortic VI remained significant after adjustment for cardiovascular risk factors: aortic VI and TB (β = 0.23; P < .001), NCB (β = 0.24; P < .001), luminal stenosis (OR, 3.40; 95% CI, 1.40-8.24; P = .007), and HRP (OR, 2.72; 95% CI, 1.08-6.83; P = .03). No association was found between aortic VI and dense-calcified coronary plaque burden.Conclusions and relevanceAortic VI is associated with broad CAD indices, suggesting that aortic VI may be a surrogate for early CAD. Larger prospective studies need to assess these associations longitudinally and examine treatment effects on these outcomes.

Project description:IntroductionThe association between physician-reported and patient-reported outcomes in patients with psoriasis is not adequately explored. Trends in PASI scores across body regions and the descriptive correspondence between physician-reported PASI components and patient-reported Psoriasis Symptom Diary are reported here.MethodsPURE is a prospective observational study in adult patients from Canada and Latin America with moderate-to-severe chronic plaque psoriasis. The study enrolled 2362 adult patients treated with secukinumab versus other approved therapies (1:1 ratio). The PASI total score, PASI sub-scores for erythema, thickening, and scaling, and PASI scores for each body region were evaluated and further correlated with disease impact using the Psoriasis Symptom Diary.ResultsSecukinumab treatment showed early reduction in the PASI total score (mean ± SD) from 13.3 ± 9.02 at baseline to 2.3 ± 3.99 at 3 months; a similar trend was observed for PASI sub-scores for erythema (4.8 ± 3.21 to 0.9 ± 1.44), thickening (4.3 ± 3.00 to 0.7 ± 1.33) and scaling (4.2 ± 3.04 to 0.7 ± 1.30). The reduction in PASI total and sub-scores were sustained up to 36 months. Psoriasis Symptom Diary component scores related to redness, cracking, and scaling showed a similar reduction from baseline at 3 months that was also sustained up to 36 months. PASI regional scores for each body region showed reduction at 3 months with disease in the lower limbs being more treatment resistant. Safety profile of secukinumab was consistent with its established safety profile without any new or unexpected signals.ConclusionsOverall, an early and sustained resolution of erythema, thickening, and scaling was observed. Improvements were evident across all body regions, with the most persistent disease seen in the lower limbs. Trends in disease severity, as assessed by physicians using PASI, broadly reflected the trend in the comparable questions of the Psoriasis Symptom Diary assessed by patients.

Project description:Background The efficacy and safety of secukinumab in patients with psoriasis has been established in randomised clinical trials. However, data on effectiveness and safety of secukinumab in Latin American real-world settings are scarce.ObjectivesTo evaluate the effectiveness and safety of secukinumab in real-world settings in patients with psoriasis in Latin America.MethodsPURE is an ongoing multinational, prospective, observational study in patients with moderate-to-severe chronic plaque psoriasis in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab and other approved therapies. The study enrolled (1:1) patients treated with secukinumab versus other approved therapies (other Tx) per local standard of care from 81 community- and hospital-based speciality sites (21 in Latin America). Here, we report effectiveness and safety outcomes with secukinumab and other Tx for plaque psoriasis for up to 12 months in a Latin American population.ResultsOverall, 187 patients were included in the analysis, 89 of whom initiated secukinumab treatment and 98 of whom received other Tx. At month 12, 84.4%, 71.1% and 53.3% of patients treated with secukinumab achieved Psoriasis Area and Severity Index (PASI) 75/90/100, respectively, compared with 66.7%, 47.9% and 29.2% of patients who received other Tx. Investigator Global Assessment (IGA) 0/1 responders in secukinumab versus other Tx were 78.3% versus 36.7% at month 3 and 81.8% versus 66.7% at month 12, respectively. Overall, the proportion of patients achieving Dermatology Life Quality Index (DLQI) 0/1 improved from 6.9% at baseline to 76.5% at month 12 in patients treated with secukinumab versus 5.6% at baseline to 54.5% at month 12 in patients on other Tx. No unexpected adverse events were reported during the 12-month observation period.ConclusionSecukinumab demonstrated real-world effectiveness and improved dermatology quality-of-life in chronic plaque psoriasis patients from Latin America.Trial registrationPURE: NCT02786186.

Project description:IntroductionSecukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab.MethodsIn the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator's Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients' quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized.ResultsBoth co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%).ConclusionThe results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis.Trial registrationClinicaltrials.gov Identifier, NCT02826603.FundingNovartis Pharma AG, Basel, Switzerland.

Dataset Information

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

Publications

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

Similar Datasets

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