Christopher Bunick, MD, PhD, on Expanding Targets in Inflammatory Skin Disease

In an interview with Dermatology Times at the South Beach Symposium 2026, Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine and editor-in-chief of Dermatology Times, discussed emerging therapeutic strategies across inflammatory skin diseases, with a particular focus on atopic dermatitis (AD), psoriasis, and hidradenitis suppurativa (HS). His comments reflect a broader shift in dermatology toward greater biological precision and higher expectations for treatment outcomes.

AD remains a biologically heterogeneous disease, driven by more than a single inflammatory pathway. As Bunick noted, “In AD, we know that the underlying pathophysiology, it’s very heterogeneous, meaning there’s multiple cytokines that drive atopic dermatitis.” While existing mono-targeted biologics—largely focused on TH2 cytokines—have transformed care, they do not address the full spectrum of disease biology in all patients. Bispecific and trispecific biologics are being developed to more comprehensively target inflammatory pathways, with the goal of achieving deeper skin clearance, improved itch and pain control, and more meaningful quality-of-life gains.

Beyond biologics, Bunick emphasized the growing importance of selective intracellular signaling inhibitors, particularly those targeting tyrosine kinase 2 (TYK2). Although TYK2 is part of the Janus kinase (JAK) family, its inhibition differs mechanistically from traditional JAK inhibitors. “What really differentiates TYK2 inhibitors from JAK inhibitors is exactly what they are targeting in this family of JAK enzymes,” he explained. Unlike JAK inhibitors that bind the kinase domain, TYK2 inhibitors act on the regulatory or allosteric domain, resulting in high selectivity and minimal overlap with other JAK enzymes.

First-generation TYK2 inhibition with deucravacitinib has already demonstrated sustained efficacy and a reassuring safety profile in psoriasis, supported by more than four years of data. According to Bunick, this includes no increased signal for malignancy, major adverse cardiovascular events, or venous thromboembolism compared with background rates. Next-generation TYK2 inhibitors, such as zasocitinib and envudeucitinib, are designed for even greater selectivity, with phase 3 data for zasocitinib anticipated soon. Acneiform eruptions and folliculitis remain observed adverse events, but are generally manageable.

Bunick also highlighted genetic evidence supporting TYK2 as a safe therapeutic target, referencing naturally occurring human variants with reduced TYK2 function that are associated with lower rates of immune-mediated disease.

Looking ahead, he expressed enthusiasm for JAK and TYK2 inhibitors in areas of unmet need, including vitiligo, alopecia areata, dermatomyositis, and HS. In HS specifically, he called for higher clinical trial benchmarks, stating, “I really wanna see the endpoint bar being raised,” and questioned whether future therapies can move beyond modest response rates toward truly transformative outcomes.

Collectively, these advances signal an evolving therapeutic landscape in dermatology—one increasingly defined by pathway specificity, improved safety, and rising expectations for durable disease control.