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Improvement of coronary-artery-plaque lipid-rich necrotic core seen with biologic therapy of psoriasis

Circulation: Cardiovascular Imaging
Reuters Health - 15/09/2020 - Biologic therapy of psoriasis is associated with reductions in coronary-artery-plaque lipid-rich necrotic core (LRNC), according to a new study.

"This is the first in-human evidence that this high-risk plaque feature can be stabilized and even reduced by treating a primary source of inflammation (the skin),” said Dr. Nehal N. Mehta of the National Heart, Lung, and Blood Institute, in Bethesda, Maryland.

“Additionally, in the group that did not receive biologic therapy, the lipid-rich necrotic core tended to worsen, suggesting that unopposed inflammation is a dangerous thing for vascular health,” he told Reuters Health by email.

LRNC is associated with increased cardiovascular events, and psoriasis is accompanied by systemic inflammation and a higher prevalence of coronary-artery disease. It remains unclear whether LRNC is affected by biologic therapy.

Dr. Mehta and colleagues used data from 209 patients in the Psoriasis Atherosclerosis and Cardiometabolic disease initiative to characterize LRNC in the coronary arteries before and one year after initiation of biologic therapy.

Biologic therapy was initiated in 124 patients, and the 85 participants who elected not to receive biologic therapy were used as controls.

At baseline, LRNC was positively associated with male sex, hypertension status, Framingham risk score and psoriasis severity.

At the one-year follow-up, patients treated with biologic therapy had significantly improved Psoriasis Area Severity Index (PASI) scores, lower high-sensitivity C-reactive protein (hs-CRP) levels, and lower glycoprotein acetylation (GlycA). Meanwhile, the untreated group experienced smaller improvements in PASI and no significant reductions in hs-CRP or GlycA, the researchers report in Circulation: Cardiovascular Imaging.

Patients who started biologic therapy had a significant decrease in mean LRNC area from 3.12 mm2 at baseline to 2.97 mm2. Mean LRNC area did not decrease significantly among patients who received no biologic therapy, however; in fact, the mean area was nominally higher at one year (3.34 mm2) than at baseline (3.12 mm2).

The mean change in LRNC with significantly different between the biologic-treated group (-0.22 mm2) and the untreated group (0.14 mm2), and this difference persisted after adjustment for PASI, Framingham risk score, BMI and statin use.

The reduction in LRNC did not differ significantly among different biologic therapies.

“It is important to keep psoriasis treated, and aggressive treatment of inflammation may favorably impact vascular health,” Dr. Mehta said.

“It is important to also screen for cardiovascular (CV) risk factors in these patients, since the combination of treating the skin disease as well as treating CV risk factors may have synergistic impact, but we just do not have this evidence yet,” he said. “These findings support performance of a large, randomized controlled clinical trial testing this hypothesis.”

The findings contrast with another new study that found an increase in serious cardiovascular (CV) events soon after initiation of ustekinumab therapy for psoriasis (https://bit.ly/2RdFfBX).

Dr. Mehta said those "findings have not been replicated" and "the IL-12-23 pathway still does not show this increased-CV-events signal in follow-up registries of patients containing over 40,000 person-years of follow-up. Finally, in our study, treatment with IL-12-23 therapy was associated with a reduction in lipid-rich necrotic core compared to not taking a biologic.”

The research was supported by a program that receives commercial funding from commercial donors including Genentech, which makes biologics.

By Will Boggs MD

SOURCE: https://bit.ly/2ZDXCVn Circulation: Cardiovascular Imaging, online September 15, 2020.

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