"Prednisone Without Side Effects": The JAK Inhibitor Ceiling in Dermatology

Last year, Matthew Zirwas, MD, director of the clinical trials and dermatitis center at Dermatologists of Greater Columbus, described ruxolitinib cream as “close to the perfect drug for atopic dermatitis” in an interview with HCPLive. He further explained the agent’s rapid-acting efficacy and a level of prescribing confidence he experienced with the agent relative to other options including steroids.¹

A year later, during the Society for Dermatology Physician Assistants (SDPA) 2024 Summer Meeting, Zirwas doubled down on his sentiment—and provided further thought on how the Janus kinase (JAK) inhibitor drug class will come to further bolster care strategies in dermatology.

In the final segment of his interview with HCPLive during SDPA 2024, Zirwas highlighted the approximate 15-minute symptom relief associated with ruxolitinib cream observed in patients with atopic dermatitis.

“If patients want an as-needed drug, right...that is the perfect as-needed drug, because, imagine if we had an acne drug where we said to our teenager, 'Hey, put this on, and by the time you go back to school in 15 minutes, your acne will be mostly better.' Or a psoriasis topical: 'Hey, put this on. By the time you get back to work, the redness and flaking will be gone.' Like that's insane, right?” Zirwas explained. “So, that's what makes it such a perfect drug.“

In terms of continuing to refine ruxolitinib cream’s capability for atopic dermatitis, Zirwas said patients could potential benefit from larger prescription containers, coinciding with a reduction of dosing regimens from twice to once-daily and a product that features less systemic absorption.

“So, even though I have no concerns about the risk associated with topical ruxolitinib, there is 6% systemic absorption,” Zirwas said. “So, if you treat a big enough area, you probably are getting some systemic JAK effect. With 60 gram tubes, the disease size that you could treat is small enough that we don't have to worry about that at all. But if we got to larger containers, we would either need a lower concentration or less systemic absorption if we wanted to use it on big body surface areas.”

In talking about further development of JAK inhibitor therapies, Zirwas highlighted the development of agents for the treatment of hidradenitis suppurativa (HS)—associated with efficacy outcomes that he has “never seen anything remotely like.”

“I mean, this has to be the way that the first investigators who did dupilumab clinical trials felt and were like, 'Oh my God.' That's what JAK inhibitors are like for HS,” Zirwas said. He cited a cohort analysis showing all patients with HS who were initiated on 15 mg upadacitinib achieved at least 50% improvement in disease severity in 12 weeks.²

“It is insane how effective these drugs are,” Zirwas said.” And don't forget, this is monotherapy. So, my firm belief is that once we really have JAKs for HS, we may put somebody on some antibiotic and a JAK, and I think that's going to have incredible efficacy. And then we stop the antibiotic and just maintain them on the JAK.”

Zirwas described the 10-second elevator pitch for JAK inhibitors in dermatology as “prednisone with no side effects.” He expressed high excitement for the time when the drug class becomes more readily available and marketed for a wider array of his patients.

“If JAK inhibitors get to someday where they're cheap and easy to prescribe, it'll be everything, right?” he said. “Like, lichen planus, granuloma annulare...all of the really hard stuff to treat is going to become pretty darn easy to treat if we get cheap, easily accessible JAK inhibitors at some point—which at some point we will. Maybe that's going to be 5-10 years from now before they go generic, you know? But it's going to make a big difference.”

Reference

1. ^{Kunzmann K. Matthew Zirwas, MD: Ruxolitinib Cream and the Eczema JAK Inhibitor Era. HCPLive. Published June 24, 2023. https://www.hcplive.com/view/matthew-zirwas-ruxolitinib-cream-eczema-jak-inhibitor-era}
2. ^{Kozera E, Flora A, Frew JW. Real-world safety and clinical response of Janus kinase inhibitor upadacitinib in the treatment of hidradenitis suppurativa: A retrospective cohort study. J Am Acad Dermatol. 2022;87(6):1440-1442. doi:10.1016/j.jaad.2022.07.047}