First-line biologic treatment of psoriasis reduces inflammation in the skin but also appears to improve three high-risk coronary plaque features, a new study suggests.
After psoriasis treatment with an interleukin (IL)-17 inhibitor, computed coronary tomography angiography (CCTA) in patients at low cardiovascular risk revealed reductions in noncalcified plaque, reductions in the plaque’s necrotic core, and increases in its fibrous cap, which makes it harder for plaques to rupture.
“What’s really cool is that these were lipid-, glucose-, and metabolic-independent effects, which means the medications over a 1-year period of time did not increase HDL or decrease blood pressure or decrease glucose,” lead investigator, Nehal N. Mehta, MD, MSCE, National, Heart, Lung, and Blood Institute, Bethesda, Maryland, said in an interview.
“These are FDA-approved medications to treat psoriasis and the coronary plaque got better,” he said. “These were ideal off-target benefits.”
The results were less robust in patients treated with anti–tumor necrosis factor (TNF) drugs, but plaques stabilized and fibrous caps increased. In those not started on biologics, however, plaques not only became more high risk but the fibrous caps got thinner over the year and necrotic cores actually worsened, Mehta said.
“So our take-home is that biologic therapy, whether it’s anti–IL-17 therapy or anti-TNF therapy, looks like it is beneficial for coronary disease,” he said. “Second, not treating your psoriasis seems to be a bad idea. But you don’t want to drink too much of your punch at this stage, and what’s needed here is a properly powered, randomized clinical trial, which we are in the early stages of planning.”
Psoriasis affects 2% to 4% of the population and is known to accelerate the risk for myocardial infarction (MI). Prior data indicate that a 40-year-old patient with severe psoriasis has about a 200% increased risk for early MI. Last year, the researchers reported that patients with psoriasis have a coronary plaque burden equivalent to that of a person about 10 years older with hyperlipidemia.
For the first time, the recent CANTOS trial also demonstrated a 15% reduction in secondary cardiovascular events by directly targeting inflammation with the IL-1β antibody canakinumab (Ilaris, Novartis). This led the present team to question whether this was due to simply reducing systemic inflammation or a more local benefit on the coronary arteries, for example, plaque modulation.
To examine this, researchers followed 84 middle-aged patients (mean, 51 years) with Framingham risk scores of 3 to 6 as part of the ongoing, observational Psoriasis, Atherosclerosis and Cardiometabolic Disease Initiative (PACI). Of these, 57 received IL-17 or anti-TNF inhibitors and 27 were treated with topical or ultraviolet light therapy. All patients were naive to biologic therapy, methotrexate, and statin therapy. A single reader blinded to treatment read CCTA scans, which were obtained at baseline and 1 year.
During 1-year follow-up, proinflammatory cytokine IL-1β levels decreased slightly but significantly in the group treated with biologics (2.6 μg/L to 2.4 μg/L; P = .03) and increased in the group not treated with biologics (1.9 μg/L to 2.5 μg/L; P = .05).
C-reactive protein declined in both groups (7.1 mg/L to 2.7 mg/L; 9.4 mg/L to 3.9 mg/L, respectively; P both comparisons < .001), first author, Youssef Elnabawi, BS, National Institutes of Health, Bethesda, reported at the Society for Cardiovascular Angiography and Interventions (SCAI) 2018 Scientific Sessions.
In the biologic group, coronary plaque volume decreased by 40% (2.5 mm2 to 1.5 mm2; P = .002) and noncalcified plaque index by about 10% (1.29 mm2 to 1.17 mm2; P = .03), while plaque volume nearly doubled in the nonbiologic group (3.3 mm2 to 6.3 mm2; P = .04) and noncalcified plaque index increased (1.09 mm2 to 1.29 mm2; P = .007).
Further, change in plaque volume was positively associated with the change in IL-1β (β = 0.56; P = .03), even after adjustment for age, sex, body mass index, low-density lipoprotein cholesterol, statins, and psoriasis treatment, Elnabawi said.
The new study builds on the CANTOS trial by introducing the concept that “inflammation is not only IL-1β,” Charalambos Antoniades, MD, PhD, University of Oxford, United Kingdom, who was not involved in the study, told theheart.org | Medscape Cardiology via email.
“Especially in chronic inflammatory diseases like psoriasis, targeting specific cytokines like IL-17 or TNF-a may have a similar effect, not only by preventing coronary plaque progression, but even by reducing the volume of existing plaques, leading to plaque regression,” he said. “Whether these changes in plaque composition or volume can lead to reduced risk for heart attacks remains to be demonstrated.”
For that, large-scale outcomes trials are needed in addition to studies to see which anti-inflammatory treatments work best for plaque regression in psoriasis, Antoniades said. Two other issues are the high cost of biologic agents and the serious side effects of these agents. “They target key features of the immune response, therefore long-term use in non-psoriasis patients is unlikely,” he added.
Although the study provides “excellent hypothesis-generating data,” Antoniades noted that it was not randomized, selection of treatments was based on severity of disease and thus may have introduced a selection bias, and the methods used for analyzing plaque had “major technical limitations, and their interpretations in nonrandomized studies should be done with caution.”
Having access to this patient population with these advanced imaging techniques is a rare combination, Mehta acknowledged. Other limitations of the study are the observational design, small patient numbers, and lack of hard events.
PACI patients will continue to be followed, and additional outcome data on inflammation and heart disease are anticipated from the Cardiovascular Inflammation Reduction Trial (CIRT), he noted. CIRT is examining whether low-dose methotrexate, which observational data have shown can reduce vascular events in the setting of rheumatoid arthritis and psoriatic arthritis, can reduce secondary MI in patients with type 2 diabetes or metabolic syndrome.
Asked to comment, Chandan Devireddy, MD, Emory University School of Medicine, Atlanta, Georgia, who was not involved in the study, said, “This is a smaller study but very interesting in their use of CT angiography, and any time you see plaque regression, that’s fairly impressive.”
“The problem with this kind of therapy is the smaller study, and if this were to be used in a larger-scale population, are there other long-term adverse effects or risks — whether it is opportunistic infections or so on and so forth — that patients may be at risk for with an immunomodulatory strategy?” he said. “Those things have to be borne out in larger-scale clinical trials.”
Mehta reports institutional research grants from AbbVie, Janssen, Celgene, and Novartis. Elnabawi reports having no relevant disclosures. Devireddy reports serving on a scientific advisory board for Medtronic and receiving travel and logistical funding for meetings from Edwards Lifesciences.
Society for Cardiovascular Angiography and Interventions (SCAI) 2018 Scientific Sessions. Presented April 26, 2018.
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