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JAKs and Biologics for AD in Geriatrics and Peds

Dr. April Armstrong discusses safety and efficacy data for using JAKs and biologics to treat atopic dermatitis in special populations.

April Armstrong, MD, Professor of Dermatology, Associate Dean For Clinical Research, Keck School of Medicine, University of Southern California, Los Angeles

“When we think about our geriatric patients, this is a very special population because they may have an increased number of comorbidities and may be more prone, for example, to laboratory abnormalities,” said April Armstrong, MD, who presented “Dupilumab and JAKs in Special Populations” as part of the International Eczema Council (IEC) subspecialty at the 31st EADV Congress 2022 in Milan, Italy.

When treating atopic dermatitis (AD) in this population, there are some differences in dose response to the FDA approved JAK inhibitors upadacitinib and abrocitinib, said Dr. Armstrong.

“For example, when we’re talking about upadacitinib monotherapy… what was found was that geriatric patients actually had similar response… [to] upadacitinib at 15 mg as well as 30 mg.”

Thus, the indicated 15-mg dose is the lowest effective dose that will keep patients safe, said Dr. Armstrong.

“We saw a bit more dose response relationship between the 100 mg of [abrocitinib] versus a 200 mg abro, and that is as one may expect—that patients who are older tended to respond better to 200 mg because it’s more drug than 100 mg.”

Notably, older patients responded comparably to younger patients treated with abrocitinib, said Dr. Armstrong.

Overall, there are some things to be aware of when using JAKs in the 65+ population.

“For example, they may be prone to rates of lower platelet counts or absolute lymphocyte counts. And they might be also at higher risk of developing, for example, herpes zoster compared to the younger patient populations.”

Biologics
For dupilumab in the geriatric AD population, one observational retrospective study showed no significant difference in response based on age, said Dr. Armstrong.

“Many of my older patients have responded well to dupilumab.”

Clinical trials of the relatively newer IL13 inhibitor tralokinumab have demonstrated a lower overall rate of adverse events for elderly patients compared to those 18 to 64 years, said Dr. Armstrong.

“You may ask why that’s the case. And what was found was that there was a lower incidence of flare of atopic dermatitis in our older patient population when they’re using tralokinumab.”

According to Dr. Armstrong, there is limited information available for using systemic medications to treat AD in immunocompromised patients.

“What has been shown in the literature are mainly case reports, for example, showing safety of dupilumab in patients with HIV or patients with hepatitis B.”

JAKs and Black Box Warnings
Black Box warnings for major cardiovascular events accompany JAK inhibitors because of risk data from the arthritis cohort, said Dr. Armstrong.

“It’s important to know that patients who have rheumatoid arthritis, for example, or psoriatic arthritis have a very different disease profile. [They] have different types of concomitant medications compared to our atopic dermatitis population.”

Thus, when using JAKs for AD patients, dermatologists should keep the reference and comparison groups in mind when interpreting adverse event rates, she said.

The Pediatric Population
Dupilumab is approved for treating patients as young as six months, said Dr. Armstrong.

“And what has been shown with dupilumab is that it works well in our children, even the very young ones.”

Although abrocitinib is only approved for adults with moderate to severe atopic dermatitis, there is clinical trial data for use in adolescents, said Dr. Armstrong.

“The data showed that there was comparable efficacy between adolescents and adults. One thing that was noted with abrocitinib in adolescents was that nausea was found to be more common in younger patients taking abrocitinib.”

Upadacitinib is approved for treating AD in patients 12 and older and has shown a dose response relationship between the 15 mg and 30 mg doses, said Dr. Armstrong.

“You do get better response (about 10% better response) with a 30-mg dose compared to the 15-mg dose in the patients who are 12 to 17 years on upadacitinib.”

Although tralokinumab is only approved for adults with moderate to severe plaque psoriasis, study data in adolescents has shown efficacy at 150 mg and 300 mg group compared to placebo.

“In summary, when we’re thinking about our patients with moderate to severe atopic dermatitis, we are seeing a growth in terms of our options for this patient population and, specifically, when we’re looking at the very special populations—the very young, the very old, in immunocompromised and those with multiple comorbidities—we are learning more and more about our current therapies.”