The future looks bright for people with psoriatic disease

| Beth Orenstein

No one has found a cure for psoriasis — yet. But several new drugs in the pipeline have dermatologists excited, because the new treatments have the potential to clear psoriasis better than anything before. Some of the drugs also show promise for treating psoriatic arthritis and have rheumatologists optimistic about what they may soon be able to offer their patients.

"In clinical trials, these medications have had very high response rates," said Dr. Abby Van Voorhees, chairwoman of the National Psoriasis Foundation Medical Board and chairwoman of dermatology at Eastern Virginia Medical School.

Some of the most effective medications for moderate to severe psoriasis available today are a type of biologic known as TNF-alpha (tumor necrosis factor-alpha) inhibitors. Biologics are derived from living cells that are cultured in a laboratory. TNF-alpha is a protein that, when produced in excess, causes rapid growth of skin cells, which leads to plaque psoriasis and/or damage to joint tissue. TNF-alpha inhibitors help stop the inflammatory cycle that causes psoriatic disease, and those approved for psoriatic disease include Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab) and Simponi (golimumab).

The drugs still in development target different proteins, or cytokines, that researchers recently discovered also play a role in the inflammation that leads to psoriatic disease. The development of these drugs confirms work researchers have conducted to get a better understanding of how the immune system works, Van Voorhees said.

"Think of it like a New England town square," she said. "There are many roads that lead you to the same center green. That's what the drugs, one that was recently approved and others that are in development, do. They get you to the same place, only by a different route."

Eight dermatologists and rheumatologists Psoriasis Advance surveyed agreed: The most promising drugs in the pipeline are those that stop the proteins identified as interleukin-17A (IL-17A) and IL-23 from triggering an inflammatory response from the immune system.

IL-17A inhibitors

Earlier this year, the U.S. Food and Drug Administration approved Cosentyx (secukinumab), a drug marketed by Novartis that works by targeting IL-17A. Four clinical trials enrolled more than 2,400 patients taking either Cosentyx or a placebo. More than 80 percent of patients taking Cosentyx saw 75 percent or more of their symptoms disappear, according to a study published in The New England Journal of Medicine in July 2014. After three months, more than 65 percent of patients taking Cosentyx rated their psoriasis symptoms at a 0 or 1, meaning that their skin was totally or almost totally clear.

Dr. Mark Lebwohl, dermatology professor at the Icahn School of Medicine at Mount Sinai and chairman emeritus of the NPF Medical Board, said drugs that target IL-17A not only work unbelievably well but also appear to be safe.

"Patients born with defects in IL-17 aren't known to have an increased risk of heart attacks or cancer. They develop yeast infections," said Lebwohl, who was involved in clinical trials of Cosentyx.

Cosentyx has few side effects, with colds and respiratory tract infections that include symptoms such as a sore throat and nasal congestion as the most common. In addition, patients with Crohn's disease should discuss with their doctor whether this medication is right for them, as it doesn't work as well as some other biologics for Crohn's disease and causes some people with the illness to have flares. And, as expected, mild or moderate yeast infections are increased, Lebwohl said.

Another drug in development that targets IL-17A is Eli Lilly's ixekizumab. Like other biologics, ixekizumab is delivered by injection under the skin. Clinical trials have shown it to be effective in helping clear skin, and researchers also are studying the drug as a treatment for psoriatic arthritis.

IL-23 Inhibitors

Stelara (ustekinumab), a biologic drug, targets IL-12 and IL-23. Some new drugs in development zero in on just IL-23. These are tildrakizumab (manufactured by Merck), guselkumab (developed by Janssen), and a Boehringer Ingelheim drug that doesn't have a name yet. The IL-23 protein is one step earlier in the immune response than IL-17, Lebwohl said. What the doctors like about IL-23 blockers is that they appear to be more targeted than those that block both IL-12 and IL-23. In animal studies, those given IL-23 blockers developed fewer tumors than those given IL-12 and IL-23 blockers.

Dr. Christopher Ritchlin, a rheumatologist and chief of the Allergy, Immunology and Rheumatology Division and the Clinical Immunology Research Center at the University of Rochester, said drugs that target IL-17 and IL-23 seem to work better for psoriasis than psoriatic arthritis.

"In clinical trials, these medications have had very high response rates."
Dr. Abby Van Voorhees, chairwoman, 
National Psoriasis Foundation Medical Board

"Psoriatic arthritis is responsive to blocking these proteins, but the magnitude of response is less than observed in patients with psoriasis," he said.

New topicals

A number of promising topical treatments also are in development for mild to moderate plaque psoriasis. One is tofacitinib, by Pfizer, a topical Janus kinase inhibitor that interferes with the signaling pathway that results in rapid skin growth. A second is a combination of nicotinamide and calcipotriene, made by the Israeli company Dermipsor. Also, LEO Pharma has submitted a drug application to the FDA for a combination of calcipotriene and betamethasone dipropionate (Taclonex) in an aerosol foam, which allows better penetration and greater efficacy than the current ointment and solution combinations, Lebwohl said.

SEE WHAT'S IN THE PIPELINE

Editor's note: Those surveyed for this article were Van Voorhees; Lebwohl; Ritchlin; Dr. Andrew Blauvelt, president and investigator of the Oregon Medical Research Center; Dr. Alexa Boer Kimball, professor of dermatology at Harvard Medical School; Dr. Jashin J. Wu, director of dermatology research at Kaiser Permanente Los Angeles Medical Center and an NPF Medical Board member; Dr. Alan Menter of Texas Dermatology Associates in Dallas; and Dr. Ron Prussick of The Washington Dermatology Center in Frederick, Maryland and an NPF Medical Board member.


Driving discovery, creating community

For more than 50 years, we’ve been driving efforts to cure psoriatic disease and improve the lives of those affected. But there’s still plenty to do! Learn how you can help our advocacy team shape the laws and policies that affect people with psoriasis and psoriatic arthritis – in your state and across the country. Help us raise funds to support research by joining Team NPF, where you can walk, run, cycle, play bingo or create your own fundraising event. If you or someone you love needs free, personalized support for living a healthier life with psoriatic disease, contact our Patient Navigation Center. And keep the National Psoriasis Foundation going strong by making a donation today. Together, we will find a cure.

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