Biologic Therapy Tied to Less Coronary Inflammation in Psoriasis

Batya Swift Yasgur MA, LSW

August 08, 2019

Anti-inflammatory biologic therapies are associated with reduced coronary inflammation in patients with psoriasis, a new study suggests.

Investigators studied 154 patients with moderate to severe psoriasis who had not been treated with biologic therapies for at least 3 months prior to baseline, comparing 52 of those patients treated with topical or light therapies (control group) with the remaining 82 who received biologic therapies (treatment group).

After 1 year, the perivascular fat index (FAI) — a novel imaging biomarker that assesses coronary inflammation, measured by coronary computed tomography angiography (CCTA) — was significantly lower in patients treated with biologic therapies than in those in the control group, independent of the presence of coronary plaque.

"We used cardiac CT to detect inflammation before and after biologic therapy for psoriasis and we compared patients with severe psoriasis treated with biologic therapies to those not treated," senior author Nehal N. Mehta, MD, MSCE, a cardiologist and Lasker Scholar NIH, and chief of the Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, Bethesda, Maryland, told theheart.org | Medscape Cardiology.

"After a year, our major finding was that coronary inflammation was decreased following therapy," he said.

The study was published online July 31 in JAMA Cardiology.

Novel Imaging Technique

Psoriasis is related to accelerated cardiovascular disease, Mehta said. "In previous research, we showed, using cardiac CT, that there is a high risk of plaque in people with psoriasis," he said.

"We have known that we could reduce atheroma volume, total plaque burden, after treatment for psoriasis, but measuring atheroma volume is a hard and limited task," he added. "We wanted to find a marker by CT that could be tracked and used to assess coronary inflammation, which is a marker for rupture-prone plaque."

CCTA image of the coronary arteries shows perivascular FAI before and after biologic therapy at 1 year in patients with excellent response to biologic therapy. (Source: Oxford Academic Cardiovascular CT Core Lab and Lab of Inflammation and Cardiometabolic Diseases at NHLBI.)

The FAI is a CT-based "novel, noninvasive imaging technique that allows for direct visualization and quantification of coronary inflammation using differential mapping of attenuation gradients in pericoronary fat," the authors write.

Mehta said that the idea for the current research came from a technological discovery in a "pioneering" study of close to 9000 people, reported by Oikonomou et al, that showed that high perivascular FAI values around the coronary arteries were predictive of all-cause and cardiac mortality.

"The study suggested that we could use a little fat pad on the outside of the artery to detect if the person had inflammation in the coronary artery," he said.

Vascular inflammation cannot be detected with commonly used imaging modalities, but phenotypic changes in perivascular adipose tissue induced by vascular inflammation can be quantified using the new coronary CTA methodology, Mehta said.

Because biologic therapy has been found to be associated with reduced noncalcified coronary plaque burden in patients with psoriasis, the researchers hypothesized that treatment with biologic psoriasis therapy would also be associated with a reduction in coronary inflammation, assessed as perivascular FAI, after 1 year of treatment.

Easily Accessible

The researchers recruited participants from an ongoing cohort study — the Psoriasis, Atherosclerosis, and Cardiometabolic Disease Initiative — from January 1, 2013 through March 31, 2019.

The analysis focused on 134 patients with moderate to severe psoriasis (mean [SD] age, 51.1 [12.1] years; 62.5% male) and at low CV risk, based on traditional risk scores.

To be included, patients could not have received biologic treatment for at least 3 months before starting biologic therapy at baseline.

The control group consisted of patients who opted not to receive biologic therapy and were treated with topical and/or light therapies only.

All participants underwent CCTA at baseline and at 1 year, which was the duration of the study period.

Perivascular FAI was measured around the proximal right coronary artery.

Of the 134 participants, 82 were treated with biologic psoriasis treatment — tumor necrosis factor-α, anti-interleukin (IL)-12/23, or anti-IL-17. The other 52 participants were in the control group.

There were no significant differences between the groups in demographic characteristics, baseline medication use, laboratory values, or baseline coronary inflammation assessed by perivascular FAI.

A total of 46 patients (27 in the treatment group and 19 in the control group) had coronary atherosclerotic plaque at baseline.

There were no significant changes seen at 1 year in body mass index, lipids, or glucose.

However, after 1 year, there were notable improvements in the treatment group, compared with the control group, in several domains.

  • There was a significant improvement in PASI score (58%; < .001) in the treatment group, with only a nonsignificant reduction in PASI score in the control group (median score, 6.0 [IQR, 3.7 - 10.0] vs 4.6 [IQR, 2.1 - 6.9]; = .10).

  • There was a reduction in high-sensitivity C-reactive protein level in the treatment group (median, 2.2 mg/L [IQR, 0.8 - 5.5mg/L] vs 1.3 mg/L [IQR, 0.7 - 3.7 mg/L]; = .03).

  • In the treatment group, a significant decrease was seen in coronary inflammation, assessed by perivascular FAI, from baseline to the completion of 1 year of therapy (median, −71.22 HU [IQR, −75.85 to −68.11 HU] vs −76.09 HU [IQR, −80.08 to −70.37 HU]; P < .001) compared with the control group (median, –71.98 HU [IQR, –77.36 to –65.64 HU] vs –72.66 HU [IQR, –78.21 to –67.44 HU]; P = .39).

The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents.

Propensity score matching replicated the previous observation that biologic therapy, not topical therapy, was associated with a significant reduction in perivascular FAI.

The perivascular fat marker has made people excited about our paper, which shows that we now have a marker that cardiologists can hang their hat on.

Perivascular FAI was "significantly attenuated" with biologic treatment during 1 year in patients both with and without coronary artery disease, the authors note.

"The perivascular fat marker has made people excited about our paper, which shows that we now have a marker that cardiologists can hang their hat on," Mehta concluded.

"It is modulated with treatment and is an easily accessible test, if you know how to use a CT scanner."

Exciting Time

Commenting on the study for theheart.org | Medscape Cardiology, Robert Kirsner, MD, PhD, professor of public health sciences and director, University of Miami Hospital and Clinics Wound Center, University of Miami Miller School of Medicine, noted that previous findings demonstrating that treating psoriasis results in cardiovascular improvements are derived from epidemiologic studies.

The current study, however, looks at "biologic phenomena, as opposed to epidemiological data," said Kirsner, who was not involved with the study.

"Treating psoriasis matters for the patients' skin and for their heart, while not treating or undertreating likely has consequences — among them, increased coronary artery inflammation and potential major cardiovascular events and death," emphasized Kirsner, who is also the chair and Harvey Blank Professor, Dr Phillip Frost Department of Dermatology & Cutaneous Surgery.

"It remains to be seen whether directly assessing coronary inflammation aids in the management of these patients beyond clearing the skin," he said.

Mehta agreed that larger studies are needed to validate their findings. He noted that a study on coronary modulation in psoriasis is being planned for 2020.

"It is an exciting time for noninvasive coronary plaque detection," he added.

The study was supported by the National Heart, Lung and Blood Institute Intramural Research Program; the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH; to the Foundation for the NIH from the Doris Duke Charitable Foundation; the American Association for Dental Research; the Colgate-Palmolive Company; Genentech; Elsevier; and other private donors. Mehta reports being a full-time US government employee and serving as a consultant to and receiving grants or other payments from Amgen, Eli Lilly, and Leo Pharma; serving as a principal investigator and/or investigator to and receiving grants and/or research funding from AbbVie, Celgene, Janssen Pharmaceuticals, Inc, and Novartis; and serving as a principal investigator and receiving grants and/or research funding from the National Institutes of Health. The other authors' disclosures are listed on the original paper. Kirsner discloses no relevant financial relationships.

JAMA Cardiology. Published online July 31, 2019. Abstract

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