Dr. Robert Sidbury discusses the latest in pediatric atopic dermatitis treatment options.
Robert Sidbury, MD, MPH, is Professor of Pediatrics and Chief of Dermatology, Seattle Children’s Hospital, University of Washington School of Medicine, Seattle, Washington
“It was interesting because literally days before I gave this talk, dupilumab was approved for the treatment of atopic dermatitis down to 6 months of age. This was really a fundamental change,” said Robert Sidbury, MD, MPH, who presented “Treating Atopic Dermatitis in Children,” during the virtual Symposium for Inflammatory Skin Disease meeting.
Dupilumab (Dupixent, Sanofi/Regeneron) was initially approved for adults, then 12-year-olds, then 6-year-olds, and now for patients as young as 6 months of age, said Dr. Sidbury.
“There have been some amazing therapeutic breakthroughs in atopic dermatitis in the last few years including topical medicine crisaborole (Eucrisa, Pfizer). It’s a nonsteroidal treatment approved down to 3 months of age for pediatric atopic dermatitis. There is no other medication that is approved for patients who are that young.”
The two older nonsteroidals—topical calcineurin inhibitors pimecrolimus (Elidel, Bausch) and tacrolimus (Protopic, Leo Pharma)—are approved for patients 2 years of age and older, said Dr. Sidbury.
“And a newer one … approved in the last year, but only down to 12 years of age, is topical ruxolitinib (Opzelura, Incyte Dermatology) for mild to moderate atopic dermatitis.”
Same Algorithm, Newer Options
The treatment algorithm hasn’t changed a lot for topical atopic dermatitis therapies, according to Dr. Sidbury.
“It still starts with topical steroids, with which all your listeners, viewers, and my colleagues are well familiar. We’ve been using them for years. For 20 years we’ve had topical calcineurin inhibitors. They are still second line, and we still use them for 2 years of age and older, with pimecrolimus for mild to moderate atopic dermatitis and tacrolimus for moderate to severe disease.”
Today there also are the options of crisaborole and the new topical Janus kinase (JAK) inhibitor ruxolitinib, said Dr. Sidbury.
“For many, the treatment algorithm hasn’t changed much but we now have some second- and third-line options that are new and different for those patients who, for whatever reason, are not responding appropriately or are having untoward side effects.”
Big Changes in Systemics
In the past, one systemic medication, prednisone, was approved for atopic dermatitis in the United States, said Dr. Sidbury.
“Systemic steroids are the least favorite treatment for all dermatologists for atopic dermatitis. [Prednisone is] not an appropriate therapy for a chronic disease like atopic dermatitis, yet it was the only systemic approved until 2017.”
There were alternatives, including nonsteroidal immunomodulators like cyclosporin or methotrexate and azathioprine or mycophenolate, and some still use those options, according to Dr. Sidbury.
“But now we have drugs like dupilumab, which seem to work better, faster, and seem to be safer. So, dupilumab certainly has leapt ahead to first line certainly for adults, in my opinion, and for children, too.”
According to Dr. Sidbury, whose center was among the study sites for the dupilumab 6-month-to-6-years-of-age approval, while many dermatologists are familiar with using dupilumab in adults, there are nuances with using it in children 6 years and younger.
“First of all, typically this drug is loaded. You’ll give a loading dose, then start with your cycle, depending on weight, with either an every-other-week or once-a-month shot. These very young patients do not get a loading dose. They just start right up with a once-a-month shot, with the dose depending on their weight.”
The efficacy in the youngest cohort is similar to that seen in older kids and adults. Side effects are similar, too, although conjunctivitis, while a recognized adverse event in young children, is not as common as in older children and adults, he said.
Another new option for atopic dermatitis is an oral medication, upadacitinib (Rinvoq, Abbvie), approved for patients 12 years of age and older, for treatment of moderate to severe atopic dermatitis, according to Dr. Sidbury.
“It’s a pill taken once a day. And it really has been extraordinary.”
In terms of efficacy, a head-to-head trial in adults suggests that upadacitinib may be even more efficacious than dupilumab, he said.1
“And upadacitinib works quicker. I’ve already had patients, and this isn’t just my experience, who after one pill or two pills [are] having a dramatic reduction in itching.”
Upadacitinib does require laboratory monitoring, he said.
In this case, “Kids who are very excited not to have to take a [dupilumab] shot anymore do have blood draws to look forward to.”
“This class of medication comes with a boxed warning, and that is something that needs to be part of shared decision-making. Parents and kids need to know that the boxed warning outlines some fairly daunting potential concerns, like malignancy, infection, cardiovascular disease, [and] clotting. Scary stuff.”
But dermatologists are savvy about putting boxed warnings into context for patients, said Dr. Sidbury.
“We’ve been doing it for 20 years with pimecrolimus and tacrolimus. So, we know how to contextualize things and that’s absolutely critical here because this boxed warning was generated in a way that is not necessarily apples to apples. It was with a different JAK inhibitor, tofacitinib (not upadacitinib or abrocitinib, the two that are approved for eczema). It was done in adults with different comorbidities, and the indication was for rheumatoid arthritis. They had lots of comorbidities which kids that we’re treating for eczema generally do not have.”
That’s not to diminish its significance, and it’s still important to have those frank conversations with parents and patients, he said.
“Left on its own without any context [of] that boxed warning, there is not a soul on this planet who would want to take it or would want their child to take it for atopic dermatitis, no matter how bad the atopic dermatitis was. So we definitely need to contextualize it because it seems to be a very promising intervention.”
Reference:
- Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial [published correction appears in JAMA Dermatol. 2022 Feb 1;158(2):219] [published correction appears in JAMA Dermatol. 2022 Feb 1;158(2):219]. JAMA Dermatol. 2021;157(9):1047-1055. doi:10.1001/jamadermatol.2021.3023.
Disclosures: Through his institution, Dr. Sidbury has been an investigator for Regeneron, UCB and Galderma. He is on the speakers’ bureau for Beiersdorf and has been a consultant for Leo Pharma.