Psoriasis drug reduces ‘bad fat’ in people with psoriasis

Apremilast has been found to reduce visceral body fat in psoriasis patients and could potentially play a role in helping improve their cardiovascular health. While weight loss is a common side effect of apremilast, what hasn’t been studied in detail is the type of body fat lost and related inflammatory markers. To answer this and questions related to cardiovascular disease (CVD), researchers investigated the association of the drug with aortic vascular inflammation cardiometabolic biomarkers and adiposity. Findings were published in JAMA Dermatology. People with psoriasis are commonly overweight or obese, and have fairly high risk of cardiovascular disease, said the study’s lead author, Dr. Joel Gelfand. He is a professor of dermatology and of epidemiology at the University of Pennsylvania Perelman School of Medicine. Read: Drug switches in the treatment of psoriasis: an analysis They are treated with various targeted immune therapies, and a question is: do any of them help lower their risk for CVD? Visceral body fat is of interest because it has characteristics that are more medically relevant than other body fat. It has inflammatory characteristics and is associated with fatty liver disease, heart attacks, cancer and atherosclerosis. Generally, apremilast is associated with a reduction in inflammatory activity in psoriasis and potentially in atherosclerosis. It is also associated with decreased body weight of 5% to 10% in 12% of psoriasis patients—an association not related to gastrointestinal (GI) symptoms (although GI symptoms are not an uncommon side effect), the study said. A phase-4, non-randomized, open-label multicentre trial was conducted with adult patients with moderate to severe chronic plaque psoriasis. Patients were recruited from seven centres across the U.S. between April 11, 2017, and Aug. 17, 2021. Participants underwent a screening period of up to four weeks and an open-label treatment period (52 weeks) with apremilast. Included were 70 patients aged 18 years and over (mean age of 47.5) who had at least 10% body surface area involvement, a Psoriasis Area and Severity Index score greater than or equal to 12 at baseline, stable disease for over two months before screening and baseline, and who were candidates for systemic therapy. They did not receive biologics within 90 days of study entry and were excluded if they already used apremilast or cholesterol-lowering medications. Of the patient population, 54 (77.1%) were male, and had mean body mass of 30.2. After starting apremilast, patients were evaluated at baseline and at weeks 4, 8, 12, 16, 28, 40, and 52. The primary outcomes were change in total aortic vascular inflammation and 68 cardiometabolic biomarkers at week 16 compared with baseline. Secondary outcomes included changes in body composition as measured by FDG-PET/CT, the study said. The researchers also looked at whether there were any changes in total aortic vascular inflammation and cardiometabolic biomarkers between up to 52 weeks. After 52 weeks of treatment, it was found that the drug was effective in treating the psoriasis and was associated with weight loss. These were expected, Dr. Gelfand told the Medical Post in an interview. However, the drug had a neutral association with aortic vascular inflammation. While this was disappointing in one respect, it was positive in that “we didn’t find harm,” he said. One of the more interesting findings was that it was associated with a 5% to 6% reduction of subcutaneous and visceral fat at 16 weeks of treatment and that this was maintained through 52 weeks. By fat type, results showed an average of a 5.32% reduction in visceral adipose tissue and a 5.53% reduction in subcutaneous adipose tissue at week 16 compared to baseline. And this reduction was maintained and stayed stable by week 52. When the researchers looked at blood-based biomarkers, they found the effects were generally favorable. “At week 16, there was a reduction in IL-1b, a proinflammatory cytokine causally linked to cardiovascular disease,” the study said. This finding was “provocative if you lower a cytokine you know is related to heart attack. But from this study we don’t know what that means in terms of reduction of cardiovascular events,” Dr. Gelfand said. There were also decreases in other inflammatory markers associated with CVD. Generally, the study is proof-of-principle and adds to our knowledge of the association between apremilast and prevention of cardiometabolic disease. The study concluded “apremilast had a neutral association with aortic vascular inflammation and variable but generally beneficial associations with cardiometabolic biomarkers, and reductions in visceral and subcutaneous fat suggest that apremilast has an overall potential benefit regarding cardiometabolic disease in patients with psoriasis.” It suggested larger placebo-controlled trials are needed. Another study published in Dermatology in 2010 also found that patients with psoriasis had significantly more visceral body fat than controls without the disease. Here, researchers in Turkey compared two groups of 46 aged-matched adults. They also reported that fasting blood sugar levels were higher in psoriasis patients than in the control patients. More recently, a study in Rheumatology in 2020 compared visceral adiposity in patients with psoriatic arthritis (PsA) and psoriasis alone and its relationship with cardiometabolic risks. This study compared 52 patients with PsA and 52 patients with psoriasis and paired controls. It found that visceral fat accumulated significantly more in people who had psoriasis alone than in those with PsA and controls.

Psoriasis drug reduces ‘bad fat’ in people with psoriasis

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