Matthew Zirwas, MD: Discussing Upadacitinib, Other JAK Inhibitors for Atopic Dermatitis

Matthew Zirwas, MD, the director of the clinical trials and dermatitis center at Dermatologists of Greater Columbus, was asked about the use of Janus kinase (JAK) inhibitors for atopic dermatitis. Therapy updates had been covered in Zirwas’s Maui Derm NP+PA Fall 2024 conference talk titled ‘Atopic Dermatitis and Itch Update 2024.’

“We got a new study with upadacitinib, which is Rinvoq, and the study compared it head to head to dupilumab,” Zirwas said. “They showed that using ‘on-label dosing,’ meaning starting people at 15 mg, and then if they're not doing amazingly at 4 weeks or 8 weeks, you bump them up to 30 mg. If we use it that way, compared to dupilumab, it gets about twice as many people to very high outcomes.”

Zirwas noted that patients saw 90% improvement in the visible aspects of their atopic dermatitis and many achieved an itch-free state. He added that about 20% of patients achieved that outcome in 16 weeks, whereas around 10% on dupilumab achieved such an outcome.

“We already had a head-to-head trial of upadacitinib versus dupilumab 30 mg dosing, so we already knew that it was more effective than dupilumab,” Zirwas explained. “We knew the same for abrocitinib. So with both of those drugs, their high dose is more effective than dupilumab and their low dose is equally-effective to dupilumab. Now the problem with the JAK inhibitors, of course, has been the boxed warning.”

Zirwas expressed that he is completely comfortable explaining to patients with atopic dermatitis that over 30,000 years of patient exposure in clinical trials for JAK inhibitors have shown zero increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), cancer, or death.

“So when I'm talking to a patient now, I will tell them, ‘You are going to get warnings with this medication from the pharmacy but, as far as we know, all of the data has shown they are not applicable to people like you taking this drug,’” he said. “‘They might be applicable to people with different diseases taking different but similar drugs, but we don't think they're applicable to you.’”

Later, Zirwas added that the only real adverse event with JAK inhibitors may be some immunosuppression related to herpes viruses such as herpes simplex or varicella zoster. He concluded that these appear to be the only 2 infections that patients are more susceptible to when treated with JAK inhibitors.

"It's why, when I start somebody on a JAK inhibitor for atopic dermatitis, I personally start them on valacyclovir 500 mg as prophylaxis against both herpes viruses, HSV and VZV," Zirwas said. "But the most important thing about the JAK inhibitors is knowing that an enormous data set is now showing no increased risk of major adverse cardiovascular events, VTE, cancer, or death."

View the full interview segment posted above to find out more about recent data in the atopic dermatitis treatment space.

The quotes used in this description were edited for the purposes of clarity.

Zirwas reported being a consultant and investigator for Arcutis Biotherapeutics, and has received grants from Amgen and UCB and personal fees from AbbVie, Dermavant, EPI Health, Galderma, Genentech/Novartis, Incyte, L’Oréal, Lilly, Pfizer, Regeneron, and Sanofi.