LAS VEGAS – There are so many psoriasis medications that have been approved or are in the experimental pipeline that it can be hard to track them all.

"I can't even keep them straight," Dr. Craig L. Leonardi said. "It's an amazing time right now."

He mapped out the major trends in psoriasis medications for physicians at a dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

Dr. Craig L. Leonardi

The armamentarium started off with T-cell inhibitors, the main one being alefacept, said Dr. Leonardi of St. Louis University. "I'm not aware of any other T-cell inhibitors that are in development right now. This seems to be a strategy that has been pushed off to the side for now."

On the other hand, psoriasis drugs involving cytokines and cytokine inhibitors are booming. A few other anti-inflammatory strategies also are being tested, including activation of the sirtuin 1 (SIRT1) protein, an oral phospholipid analog, an oral phosphodiesterase inhibitor, and a drug that inhibits Janus kinase (JAK) 1 and 3.

Cytokines: "Cytokines and cytokine inhibitors are exploding," Dr. Leonardi said. The five approved tumor necrosis factor (TNF) antagonists – adalimumab, certolizumab, etanercept, infliximab, and golimumab – "have great utility," he said.

There are two drugs that block both interleukins (IL) 12 and 23. Ustekinumab is approved, and Abbott Laboratories in January 2011 withdrew its biologics license application for briakinumab to perform additional studies at the request of regulators. These two drugs seem to have a "class effect" associated with increased risk of major cardiovascular events, Dr. Leonardi said.

Two other experimental drugs inhibit just IL-23. "These drugs are not interacting with IL-12 at all. If the cardiovascular signal we have seen with briakinumab and with ustekinumab is real, maybe it has to do with IL-12 more than IL-23. Maybe we'll see an improved safety profile for targeting just IL-23," he said.

Trials are underway of three drugs that inhibit IL-17 and one that targets the IL-17 receptor.

"The IL-23 drugs, IL-17 drugs, and IL-17 receptor blocker drug have a lot of briakinumab/ustekinumab feel in terms of efficacy," Dr. Leonardi said. The studies are blinded, so he doesn't know which patients are getting drug or placebo, but he's noticed that in some patients "amazing things are happening to skin and they're happening fast. This is going to be a great moment for many psoriasis sufferers" if these drugs fulfill the promises he thinks he's glimpsed.

Another trial is studying an IL-22 blocking agent.

In other categories, the novel agents being studied are oral medications, "That's a good thing for those that like that approach, but when you use oral medication, you lose a lot of the specificity that we've come to really expect with our biologic agents," he said.

Resveratrol: This compound is believed to activate SIRT1, which may have anti-inflammatory properties. Preliminary trials are underway.

VB-201: The first drug in its class, VB-201 by Vascular Biogenics is an oral phospholipid analog that downregulates production of proinflammatory cytokines by mature dendritic cells. It inhibits the shared p40 subunit of IL-12 and IL-23, and is in preliminary trials for psoriasis.

02/04/11  

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EXPERT ANALYSIS FROM THE LAS VEGAS DERMATOLOGY SEMINAR SPONSORED BY SDEF

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