Advances in psoriasis treatments, research examined

Jashin J. Wu, MD: “Patients need to know the risks of the disease, not just risks of the treatment.”

Clinicians and researchers have targeted psoriasis in recent years, leading to the development of many new treatments. Advances include the development of biologics, learning about the effect of biologics and psoriasis on vascular inflammation, and genetic links between psoriasis and autoimmune disorders. However, challenges, such as the high cost of biologics and biosimilars, have slowed progress.

Those advances and challenges were examined March 6 during “Psoriasis: Updates in Biologic Therapy, Comorbidities, Genetics, and Biosimilars” (F149). The session featured four speakers — one in each area — taking an in-depth look at recent developments.

Cost savings of biosimilars not seen in U.S.
Psoriasis can be seen as the poster child for biologics because they have revolutionized the treatment of patients suffering from a painful chronic condition, but that revolution came at a price — literally.

Biologics are effective, but they are expensive. Biosimilars were developed to provide comparable treatment at a lower cost. However, patients in the U.S. are not seeing a cost savings with biosimilars even though greater cost savings are seen with biosimilar use in other countries, said Jashin J. Wu, MD, the session director.

Speaker Andrew Blauvelt, MD, MBA, is a dermatologist and president of the Oregon Medical Research Center. He defined a biosimilar as a biological product that is highly similar to a reference product, but with minor differences in clinically inactive components.

However, greater use of biosimilars has been slowed by concerns that even small manufacturing differences may change the nature of the drug, Dr. Blauvelt said. In addition, even though the Food and Drug Administration (FDA) has approved biosimilars for infliximab, etanercept, and adalimumab after comparator equivalence trials, FDA marketing guidelines are being debated in U.S. courts and state legislatures.

The result is that these debates are slowing the use of biosimilars as well as the promise of their decreased cost and increased access, he said. (To learn more about these debates, visit www.aad.org/dw/monthly/2016/november/will-the-biosimilars-pathway-lead-to-savings.)

Concerns about biologics
Three biologic agents with outstanding safety profiles are available and commonly used in the U.S., but they are not being used due to concerns about the risks of taking the drugs, said speaker John Koo, MD, professor of dermatology at the University of California, San Francisco.

“Many even more efficacious biologics are being developed. So far, they all have excellent safety data. The patients need to know the risks of the disease, not just risks of the treatment. In view of this, psoriasis patients need not be undertreated,” Dr. Koo said.

Even though six biologics — etanercept, adalimumab, ustekinumab, secukinumab, brodalumab, and ixekizumab — are have been approved by the Food and Drug Administration to treat psoriasis, less than 6 percent of patients are using them, according to a 2014 study. There is a fear of their use among physicians and patients because of FDA warnings, he said.

Among those warning are an increased risk of serious infections that could lead to hospitalization or death for adalimumab. However, a study published in 2015 concluded that “few adverse effects of the biologic agents etanercept, adalimumab, and ustekinumab have reached statistical significance.”

“When patients have no idea about comorbidities,” Dr. Koo said, “patients only know how to worry about the risks of treatment, not realizing the risk of disease may be more deadly and disabling than the risk of treatment.”

Comorbidities are common among patients
Patients with psoriasis have many comorbidities, including autoimmune hepatitis, chronic pancreatitis, and avascular necrosis. Patients with a family history of cardiovascular disease have a greater risk of major adverse cardiac events (MACE).

On a more positive note, TNF inhibitors are associated with a decreased risk of endothelial dysfunction, arterial stiffness, MACE, and c-reactive protein, said Dr. Wu, founding director of dermatology research and director of the Psoriasis Clinic department of dermatology at Kaiser Permanente Los Angeles Medical Center.

In addition, the use of ustekinumab and TNF inhibitors are associated with a reduction in atherosclerosis, and psoriasis therapy may help patients improve HDL cholesterol composition and function, he said.

Results of the Vascular Inflammation in Psoriasis trial were released during the 2017 AAD Annual Meeting. Its results showed that patients taking adalimumab did not have improvements in vascular inflammation, but patients receiving phototherapy did have improved vascular inflammation

Dr. Wu reminded dermatologists that the National Psoriasis Foundation recommends that patients with psoriasis should have their blood pressure, pulse, and body mass index checked every two years. Every five years, they should have their fasting blood glucose and lipid levels checked, unless they have additional risk factors. If they have additional risk factors, those checks should take place every two years.

Genetic research providing more clues
An increased knowledge of genetics has identified at least 64 psoriasis genes that are affecting immune pathways, and patients with psoriasis who have these genetic issues often have autoimmune diseases, said Wilson Liao, MD, an associate professor of dermatology at the University of California, San Francisco.

Researchers have found that psoriasis genes cluster to biological pathways, and these psoriasis genes are shared with autoimmune and cardiovascular diseases. Autoimmune diseases that have genes that overlap with psoriasis include celiac disease, lupus, rheumatoid arthritis, and Crohn’s disease. Among the cardiometabolic comorbidities of patients with psoriasis are atherosclerosis, hypertension, myocardia infarction, obesity, dyslipidemia, and diabetes.

A focus on the HLA gene system is helping researchers learn more about psoriasis autoantigens that are thought to be triggers for the disease. These advances could lead to whole genome sequencing and learning more about interactions among genes and between genes and the environment. The result could be the development of pharmacogenetics for future treatments, Dr. Liao said.

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