Monoclonal Antibodies Targeting Interleukin Cytokines Effective in Trials

When Shawn Ingram’s doctor sent him home with steroids and a recommendation for dandruff shampoo, his frustration would be all too familiar to many psoriasis patients and their physicians.

“I was covered from head to toe. The steroids barely eased the itching for a few days, and then it came back with a vengeance. I couldn’t even sit down for more than a few minutes without the skin coming off the back of my thighs. Every time I took off a shirt, it was covered in white flakes,” Ingram said.

“When I heard there wasn’t anything else that could help me, I knew I had to find something. The constant itching was torment. So I searched online and read about the clinical trials Dr. Elewski is doing at UAB. One injection and the itching was gone in a few days. Within a couple of weeks, my skin started clearing. By the time I went back a month later, the symptoms were gone.”

Ingram’s skin has been clear for a year now, and it is staying clear with an injection once every three months. His success story isn’t the only one Boni Elewski, MD is seeing in the clinical trials she has been conducting on several drugs targeting Interleukin-17 and 23.

The UAB professor of dermatology is the principal investigator for one of two studies on Secukinumab recently published in the New England Journal of Medicine, and she has conducted trials on related drugs including Brodalumab and Ixekizumab, which are expected to soon receive FDA approval.

“This is going to be a life changer for many patients,” Elewski said. “The phase two data on this family of drugs looked promising, and the response we’ve seen so far in phase three trials has been very encouraging. A statistically significant percentage of patients with moderate to severe psoriasis treated with Secukinumab achieved skin clearance of up to 90 percent or more after 12 weeks, and with continued treatment, a majority of these patients were maintaining those results at one year.”

In normal skin, the interlukin-17 cytokine activates the body’s immune system to heal cuts, scrapes and other injuries. However, people with psoriasis lesions can have many times as much IL-17 as those without. The healing process becomes a continuing loop of new cell production and inflammation.

Secukinumab (Novartis) and Ixekizumab (Eli Lilly) target IL-17, while Brodalumab (Amgen) targets a specific receptor that binds to the IL-17 cytokine.

“So far, these IL-17 inhibitors have been well tolerated. Since the new drugs are more targeted to only one cytokine, and there are a number of healthy people in the world who don’t even have IL-17, we feel the drugs are likely to score well on safety, though we will be evaluating five-year data to confirm that,” Elewski said.

“There seems to be a genetic predisposition for psoriasis in some people. Along the way, something triggers the predisposition. It can be an illness, a medication, drinking alcohol or smoking. Smoking particularly seems to be associated with greater difficulty in clearing psoriasis lesions. Stress seems to trigger flares.

“Psoriasis also tends to come with other co-morbidities, so we try to make sure our participants have good follow-up with a physician who can monitor their overall health. The arthritis some patients experience turns out to be psoriatic arthritis. Metabolic syndrome is a frequent factor, so we may send participants to a nutritionist or get evaluations for other conditions that may be affecting their health.”

For patients who are needle phobic or may be in other situations where injections may be difficult, such as soldiers in combat zones, an oral drug already approved for arthritis may soon be approved for psoriasis.

“Pfizer’s Tofacitinab works by a different mechanism and is somewhat slower, but it seems to work as well as high dose Embrel,” Elewski said. “What we need to let patients know is that with so many new options that will soon be available, there is hope. There should be a good choice for just about everybody.”

The drug that brought Shawn Ingram so much relief, MK-3222 developed by Merck, takes a slightly different approach, but from a similar strategy. Instead of IL-17, it targets IL-23. It is a high-affinity humanized anti-IL-23p19 monoclonal antibody that doesn't bind human IL-12. It recently earned its official name, Tildrakizumab, and is one of the more recent weapons in the psoriasis arsenal that are now in clinical trials.

“Severe psoriasis can have such an impact on everyday life—not only the physical discomfort, but also social and emotional aspects, employment and finances, and the person’s self-image,” Elewski said. “One young woman came in covered head to toe in sweats and a hoodie. She had never had a date. She hadn’t been allowed to swim in a pool because her skin looked so bad. A month after the first injection, she came back wearing a tank top. She has a boyfriend. We all burst into tears and hugs.

“Another patient was homeless. He smelled bad because no one, not even relatives, would let him use a shower because his skin was shedding so badly. He came back the next visit, and he was clean. His skin was healing. Now he has a job. He has a girlfriend. He has a life.”