Matthew Zirwas, MD: Ruxolitinib Cream and the Eczema JAK Inhibitor Era

Janus kinase (JAK) inhibitors have been established a leading drug class in a number of chronic skin diseases. Recent data lends to one researcher’s perspective that one JAK inhibitor’s efficacy in eczema sets it in its own class—and another JAK inhibitor’s safety risks are not actually applicable to the rest available in dermatologic care.

In the final segment of an interview with HCPLive during the Maui Derm 2023 NP + PA Summer Conference in Colorado Springs this week, Matthew Zirwas, MD, director of the clinical trials and dermatitis center at Dermatologists of Greater Columbus, explained why he believes the greatest change to adult atopic dermatitis management in the last 5 years has been the introduction of topical ruxolitinib.

“As I think of topical roflumilast as close to the perfect drug for seborrheic dermatitis, topical ruxolinitib is close to the perfect drug for atopic dermatitis,” Zirwas said. He cited data from Incyte showing itch relief within 15 minutes of application with the agent.

“(It’s) giving them confidence of that kind of rapid relief with a drug they’re not afraid to use—because steroids work fast and well too, but patients are afraid to put them on,” he said.

Zirwas emphasized the benefit of ruxolitinib being associated with approximately 80% of treated patients achieving clear or almost clear skin when administered by as-needed regimens, calling it “just incredible that we’ve got that.”

“So what you tell the patient is, ‘Hey, put this on anytime you’ve got eczema, wherever you’ve got eczema.’ And there’s a 75-80% chance they are clear (of disease).”

In general, Zirwas stressed that the way by which systemic JAK inhibitors are discussed in dermatology is changing as it relates to the previously understood benefit-risk profile.

“The data are that tofacitinib is the only JAK inhibitor to have shown increased risk of (major adverse cardiovascular events) and venous thromboembolic (VTE) disease,” Zirwas said. “The only JAK that has shown an increase in those happens to be the only JAK that blocks the JAK3 (pathway).”

All other available JAK inhibitors target the 1 and/or 2 pathways, Zirwas noted, and have even been shown to reduce the risk of MACE or VTE in treated patients relative to tofacitinib.

“So it really is now becoming clear—and it’s not 100%, but extremely likely—that the MACE and VTE risk associated with tofacitinib was due to the JAK3 inhibition,” Zirwas said. “The drugs we have in dermatology are JAK1 and JAK2 inhibitors. So for that reason, and that none of the data has shown an increased risk, I really now think of the JAK inhibitors we have in dermatology as having zero risk of MACE or VTE.”

Zirwas did stress that the JAK1 and JAK2 inhibitors are still immunosuppressive and warrant discussion between clinicians and patients regarding safety risks prior to initiation. But to his perspective, dermatology patients have 2 fewer adverse events risks to worry about going forward.

“It really has now become, to me, a JAK3 problem, and we are not impacting JAK3 in dermatology,” he said.