Association Between Early Severe Cardiovascular Events and the Initiation of Treatment With the Anti–Interleukin 12/23p40 Antibody Ustekinumab

Poizeau, Florence; Nowak, Emmanuel; Kerbrat, Sandrine; Nautout, Béranger Le; Droitcourt, Catherine; Drici, Milou‐Daniel; Sbidian, É.; Guillot, B.; Bachelez, H.; Ait‐Oufella, Hafid; Happe, André; Oger, Emmanuel; Dupuy, Alain

doi:10.1001/jamadermatol.2020.2977

Cited by 59 publications

(52 citation statements)

References 49 publications

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“…More recently, a French retrospective case-time-control study compared the risk of acute coronary syndrome or stroke in the 6 months before and after initiation of ustekinumab. The study found an increased risk for these events in patients considered high cardiovascular risk (two risk factors or personal history of acute coronary syndrome or stroke), positing a role for IL-17 in stabilizing atherosclerotic plaques [107]. In consideration of the latest study, mindful evaluation of risk factors such as hypertension, hyperlipidemia, and diabetes mellitus is important and alternatives to ustekinumab should be identified in high-risk patients.…”

Section: Discussionmentioning

confidence: 98%

Use of IL-23 Inhibitors for the Treatment of Plaque Psoriasis and Psoriatic Arthritis: A Comprehensive Review

2020

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Psoriasis is a common inflammatory skin disease with multiple comorbidities, including psoriatic arthritis and coronary artery disease, that can severely impact an individual’s quality of life and daily functioning. In recent years, enhanced understanding of the pathogenesis of psoriasis, especially the role of T helper 17 cells, has resulted in the development of new classes of biologic drugs targeting modulators along its disease pathway. Among these, inhibitors of interleukin-23 (e.g., ustekinumab, guselkumab, tildrakizumab, and risankizumab) have emerged as safe and effective options for the treatment of moderate-to-severe plaque psoriasis; ustekinumab and guselkumab have additionally been approved to treat psoriatic arthritis. Selective interleukin-23 inhibitors require less frequent dosing than interleukin-17 inhibitors and may possess a more favorable risk profile without an increased risk of candidiasis or inflammatory bowel disease. Overall, these highly effective medications are contributing to a rising standard for psoriasis outcomes through resolution of skin lesions and joint manifestations and improvement of patient quality of life.

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Section: Discussionmentioning

confidence: 98%

Use of IL-23 Inhibitors for the Treatment of Plaque Psoriasis and Psoriatic Arthritis: A Comprehensive Review

2020

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“…CD4 + T helper 1 (T H 1) cells have pro-atherogenic functions, whereas T reg cells canonically have atheroprotective roles, although T reg cell subsets with detrimental effects in atherosclerosis have been described 34 . Other CD4 + T cell subsets including T H 2 cells and T H 17 cells are present in the plaque microenvironment but their role in atherosclerosis is still controversial and mechanistically not fully understood [34][35][36][37][38] . In addition to macrophages and T cells, other innate and adaptive immune cells contribute to the pathogenesis of atherosclerosis, including neutrophils, natural killer (NK) T cells and B cells, and less clearly NK cells, and the role of these cells in atherosclerosis has been extensively reviewed 19,[39][40][41][42][43] .…”

Section: Key Pointsmentioning

confidence: 99%

Immune cell profiling in atherosclerosis: role in research and precision medicine

Fernandez

Giannarelli

2021

Nat Rev Cardiol

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Inflammation is intimately involved at all stages of atherosclerosis and remains a substantial residual cardiovascular risk factor in optimally treated patients. The proof of concept that targeting inflammation reduces cardiovascular events in patients with a history of myocardial infarction has highlighted the urgent need to identify new immunotherapies to treat patients with atherosclerotic cardiovascular disease. Importantly, emerging data from new clinical trials show that successful immunotherapies for atherosclerosis need to be tailored to the specific immune alterations in distinct groups of patients. In this Review, we discuss how single-cell technologies -such as single-cell mass cytometry, single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing -are ideal for mapping the cellular and molecular composition of human atherosclerotic plaques and how these data can aid in the discovery of new precise immunotherapies. We also argue that single-cell data from studies in humans need to be rigorously validated in relevant experimental models, including rapidly emerging single-cell CRISPR screening technologies and mouse models of atherosclerosis. Finally, we discuss the importance of implementing single-cell immune monitoring tools in early phases of drug development to aid in the precise selection of the target patient population for data-driven translation into randomized clinical trials and the successful translation of new immunotherapies into the clinic.

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“…In patients with ACS, low levels of IL-17 are associated with an increased risk of death and myocardial infarction [ 41 ]. In agreement with a pro-stabilizing role of IL-17, severe cardiovascular events have been recently reported in patients with a high cardiovascular risk after the initiation of treatment with ustekinumab (anti-IL-12/23p40 antibody), which targets the IL-17 pathway [ 42 ].…”

Section: Th1/th2/th17 Subsetsmentioning

confidence: 83%

Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

Ait‐Oufella

Lavillegrand

Tedgui

2021

Cells

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Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.

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Association Between Early Severe Cardiovascular Events and the Initiation of Treatment With the Anti–Interleukin 12/23p40 Antibody Ustekinumab

Cited by 59 publications

References 49 publications

Use of IL-23 Inhibitors for the Treatment of Plaque Psoriasis and Psoriatic Arthritis: A Comprehensive Review

Use of IL-23 Inhibitors for the Treatment of Plaque Psoriasis and Psoriatic Arthritis: A Comprehensive Review

Immune cell profiling in atherosclerosis: role in research and precision medicine

Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

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