Marcia Frellick

October 27, 2017

BOSTON — Two new drugs for atopic dermatitis are changing treatment for patients — who for decades have had few options — less than a year after they were approved by the US Food and Drug Administration (FDA).

Dupilumab (Dupixent, Regeneron), the first biologic for atopic dermatitis, was approved in March for the treatment of moderate to severe disease. The injectable can be used with or without topical corticosteroids.

Crisaborole (Eucrisa, Pfizer), a phosphodiesterase 4 (PDE4) inhibitor, was approved in December 2016 for the treatment of mild to moderate atopic dermatitis in patients at least 2 years of age. It was the first anti-inflammatory medication approved for this indication in more than 15 years.

And there are other drugs currently in late-stage clinical trials in the pipeline, said Lynda Schneider, MD, professor of pediatrics at Harvard Medical School and director of the atopic dermatitis center at Boston Children's Hospital.

"Dupilumab has been living up to expectations," and the mode of delivery — injection — has not been a substantial barrier, she said here at the American College of Allergy, Asthma & Immunology 2017 Annual Scientific Meeting.

"There are definitely patients who have not wanted the injection, but most of the adult patients who have very severe disease and have suffered a long time are okay with injections," she told Medscape Medical News.

For crisaborole, Dr Schneider recommends that a short course of topical steroids be used first, and that the ointment not be applied to acutely inflamed skin because patients sometimes report stinging.

"I do tell patients that they may notice a little irritation initially, but to keep going because it often seems to resolve," she said.

Substantial Shift in Treatment

"There are a number of other exciting medications in trials," Dr Schneider reported, including several monoclonal antibodies. Some are in phase 2 trials, but one — tralokinumab, which targets the cytokine interleukin-13 receptor — has reached phase 3.

The Janus kinase (JAK) inhibitor upadacitinib (ABT-494, AbbVie) is being studied as a once-daily therapy for atopic dermatitis, and patients will likely prefer the oral formulation over injection. ABT-494 met the primary end point in a phase 2b study, and a phase 3 study is planned for 2018, she said. There are other JAK inhibitors, both oral and topical, in phase 2 trials.

More information will be available when direct-comparison studies of the drugs are done, she added.

"If we learn more about phenotyping for atopic dermatitis, we may be able to better understand which drugs are best for which patients," said Dr Schneider.

The new options represent a substantial shift in treatment, said Mark Boguniewicz, MD, from Children's Hospital Colorado in Aurora and National Jewish Health in Denver.

We are incredibly excited. Dupilumab has been a game changer.

"We are incredibly excited," he told Medscape Medical News. "Dupilumab has been a game changer. These were adults who had, on average, 20 years of atopic dermatitis."

Many people have misunderstood results from pivotal trials in which nearly 40% of the study groups achieved the primary end point of an Investigator's Global Assessment score of clear or almost clear at 16 weeks and a score at least 2 points lower than it was at baseline, he said.

That does not mean that 60% of the participants did not respond to dupilumab, as many people think, he explained, because the bar was set higher than it was in other atopic dermatitis trials.

"You could have patients with severe disease going to moderate, or severe going to mild. They wouldn't be included in the primary end point," said Dr Boguniewicz.

So far, the drug is approved only for people 18 years and older, but studies are underway that look at the use of dupilumab in children as young as 6 years, he added.

Crisaborole, he said, appeals to parents who want an alternative to topical steroids.

Parents also have concerns about FDA black-box warnings for topical calcineurin inhibitors. The warning is controversial, he pointed out, but "we're stuck with it for now."

In contrast, crisaborole is nonsteroidal and does not have a black-box warning or any restriction on length of use, he added.

Maria Garcia-Lloret, MD, a pediatric allergist at the Ronald Reagan UCLA Medical Center in Los Angeles, said she has prescribed both drugs to a few patients. Results have ranged from good to "miraculous," in the case of one dupilumab patient who had been living with severe atopic dermatitis for more than 20 years.

Dupilumab is very expensive — about $37,000 a year — but so far, insurance has covered it for her patients, she told Medscape Medical News.

Crisaborole is especially helpful with itching. "That's what drives patients crazy, and when they scratch, they make themselves worse," she explained.

"Patients with atopic dermatitis have been suffering for years," Dr Garcia-Lloret added. "I went into allergy in part because of that; I saw families torn apart with little kids with atopic derm. These two drugs offer hope."

Dr Schneider is an investigator for Astellas and Regeneron; has received grants from Food Allergy Research and Education (FARE), Genentech, and DBV Technologies; and is on the pharmaceutical advisory board of Pfizer. Dr Boguniewicz has been involved with studies of crisaborole and the dupilumab trial involving children. Dr Garcia-Lloret has disclosed no relevant financial relationships.

American College of Allergy, Asthma & Immunology (ACAAI) 2017 Annual Scientific Meeting. Presented October 26, 2017.

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