Commentary: Does biologic treatment of psoriasis lower the risk of cardiovascular events and mortality?

Gelfand, Joel M.

doi:10.1016/j.jaad.2018.03.046

Cited by 17 publications

(14 citation statements)

References 9 publications

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“…Historically, the sponsor has evaluated serious MACEs in psoriatic patients who have increased risk for occlusive vascular diseases [ 30 , 31 ], likely resulting from higher rates of cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, obesity, smoking) and the disease itself representing an independent risk factor [ 32 ]. In a systematic review and meta-analysis of 11 observational studies ( n = 32,973), cardiovascular and cerebrovascular morbidity were increased by 43% and 22%, respectively, in PsA patients versus the general population [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn’s Disease: An Integrated Analysis of Phase II/III Clinical Development Programs

et al. 2019

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Introduction Theoretical risks of biologic agents remain under study. Objective The aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials. Methods Patients had moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) (± methotrexate), or moderate-to-severe Crohn’s disease (CD; failed/intolerant of immunomodulators/corticosteroids). Psoriatic patients received subcutaneous ustekinumab 45/90 mg or placebo, generally at week 0, week 4, then every 12 weeks thereafter, while those with CD received a single intravenous ustekinumab dose (130 mg or weight range-based dosing of approximately 6 mg/kg) or placebo induction dose at week 0, followed by subcutaneous ustekinumab 90 mg at week 8 and every 8/12 weeks thereafter. The incidence rates of a priori-defined safety events were integrated post hoc (adjusted for duration of follow-up, reported per 100 patient-years [PYs]). Results Among 6280 enrolled patients, 5884 ustekinumab-treated patients (psoriasis: 3117; PsA: 1018; CD: 1749) contributed 4521 PYs versus 674 PYs in placebo-treated patients through year 1 (829 PYs and 385 PYs during 8- to 16-week controlled periods). Combined across diseases among ustekinumab- versus placebo-treated patients, respective incidences/100 PYs (95% confidence intervals) of infections were 125.4 (122.2–128.7) versus 129.4 (120.9–138.3) through year 1, and not meaningfully increased in patients who did versus those who did not receive methotrexate (92.5 [84.2–101.5] vs. 115.3 [109.9–121.0]), or significantly increased in patients who did versus those who did not receive corticosteroids (116.3 [107.3–125.9] vs. 107.3 [102.0–112.8]) at baseline. Major adverse cardiovascular events (0.5 [0.3–0.7] vs. 0.3 [0.0–1.1]), malignancies (0.4 [0.2–0.6] vs. 0.2 [0.0–0.8]), and deaths (0.1 [0.0–0.3] vs. 0.0 [0.0–0.4]) were rare across indications. Conclusions Ustekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications. Trial Registrations ClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355.

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Section: Discussionmentioning

confidence: 99%

Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn’s Disease: An Integrated Analysis of Phase II/III Clinical Development Programs

et al. 2019

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“…Although these genes have been previously identified in PTs, 44,45 changes with secukinumab predict cleared plaque skin should have a markedly improved ability to metabolize circulating lipids and possibly lower long-term risk of comorbid cardiovascular and metabolic complications. 46 There are several reports on the effects of immune-modulating therapies on psoriasis histopathology, but few have correlated clinical and histologic changes with transcriptomic changes at clinically relevant and approved drug doses. One week after administration of cyclosporine, psoriatic LS specimens showed reductions in KC hyperplasia, mitoses, lymphocytic and perivascular mononuclear infiltrates, and antigen-presenting cells and complete clearance of neutrophils.…”

Section: Discussionmentioning

confidence: 99%

IL-17A inhibition by secukinumab induces early clinical, histopathologic, and molecular resolution of psoriasis

Krueger

Wharton

Schlitt

et al. 2019

Journal of Allergy and Clinical Immunology

138

106

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and East Hanover, NJ GRAPHICAL ABSTRACT Background: Hyperactivity of the IL-23/IL-17 axis is central to plaque psoriasis pathogenesis. Secukinumab, a fully human mAb that selectively inhibits IL-17A, is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Secukinumab improves the complete spectrum of psoriasis manifestations, with durable clinical responses beyond 5 years From a the

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“…Initial studies of IL-17A inhibitors in patients with psoriasis have shown no impact (with large confidence intervals [CIs]) on major adverse CV events (OR 1.00, 95% CI ¼ 0.09e11.09) during the placebocontrolled portion of clinical studies (Strober et al, 2017). However, much larger and long-term studies in humans will be necessary to determine the true impact of IL-17 inhibition on CVD (Gelfand, 2018;Rungapiromnan et al, 2017). Thus, how inhibition of IL-17 modulates CV risk in humans with psoriasis also remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

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

Gelfand

Shin

Duffin

et al. 2020

Journal of Investigative Dermatology

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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 18 F-2-fluorodeoxyglucoseepositron 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 e0.053 (95% confidence interval ¼ e0.169 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-a (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.

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Commentary: Does biologic treatment of psoriasis lower the risk of cardiovascular events and mortality?

Cited by 17 publications

References 9 publications

Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn’s Disease: An Integrated Analysis of Phase II/III Clinical Development Programs

Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn’s Disease: An Integrated Analysis of Phase II/III Clinical Development Programs

IL-17A inhibition by secukinumab induces early clinical, histopathologic, and molecular resolution of psoriasis

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

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