JAK inhibitors have ‘untapped potential’ in treatment of inflammatory skin diseases
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Key takeaways:
- JAK inhibitors inhibit a broader cytokine profile than other therapies.
- Patients treated with JAK inhibitors for atopic dermatitis had better outcomes than those treated with biologics.
MIAMI BEACH, Fla. — Janus kinase inhibitors have a unique mechanism of action, giving them the potential to push the boundaries of efficacy in the treatment of inflammatory skin diseases, according to a speaker at South Beach Symposium.
“We need a new mindset in dermatology about [Janus kinase (JAK)] inhibitors,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine and South Beach Symposium senior planning committee member, said during a presentation.
According to Bunick, JAK inhibitors display “untapped potential” because they have a unique ability to target and inhibit a broader cytokine profile than other therapies.
In atopic dermatitis, for example, patients experience inflammation from different cytokine upregulations including interleukin-4, IL-13, IL-31, IL-22, thymic stromal lymphopoietin and interferon-gamma, which fall into the T-helper (Th)2, Th22 and Th1 cytokine categories. And, while biologics such as dupilumab and nemolizumab may inhibit some of those cytokines, JAK inhibitors such as upadacitinib and abrocitinib inhibit all of them.
In fact, according to a study highlighted by Bunick from the Journal of the American Academy of Dermatology, of 61 patients with AD, 74% had a partial or incomplete response to dupilumab and demonstrated an upregulation of Th1, Th17 and Th22 cytokines — profiles which dupilumab do not target.
On the other hand, in a recent network meta-analysis looking at the systemic therapies for moderate to severe AD in more than 7,000 patients, only JAK inhibitors had more than 50% and 40% of patients achieve EASI 75 and EASI 90, respectively, compared with other treatments, including biologics.
“I think this is where we see the excitement of unlocking the potential of JAK inhibitors,” Bunick said. “What’s happening here is we are seeing a pushing of the boundaries of efficacy.”
In addition to improving AD, JAK inhibitors produced the highest itch relief responses among patients — an outcome that Bunick refers to as the “JAKi Frost.”
“The first thing you should think about when you think about JAK inhibitors should not be box warnings,” Bunick concluded. “The first thing you should think about is that JAK inhibitors have the ability to cool down the inflammation and itch of inflammatory skin disease.”