New Therapies Targeting OX40 Pathway Offer Hope for Atopic Dermatitis | Fall Clinical Derm 2025

Shawn Kwatra, M.D., professor and chair of dermatology at the University of Maryland School of Medicine, discussed new therapies that target the OX40 ligand (OX40L) signaling pathway for atopic dermatitis (AD). The pathway plays a key role in driving chronic inflammation and itching in the skin.

According to the National Eczema Association, AD is the most common form of eczema, with 16.5 million adults in the U.S. being affected by the condition. There are also 9.6 million U.S. children under the age of 18 who have AD, and one-third have moderate to severe disease.

At the 2025 Fall Clinical Dermatology Conference in Las Vegas, Kwatra presented in the last couple of days his latest findings on how targeting OX40 could help patients.

He shared that OX40L is a protein on immune cells that connects with another protein, OX40, to activate and extend immune responses. When this “handshake” between cells goes on too long, it can trigger ongoing inflammation, itch and discomfort, even after the skin should have healed.

“OX40 and OX40 ligand are like a sticky handshake between immune cells that won’t let go,” Kwatra told Managed Healthcare Executive. “New treatments are learning how to release that handshake.”

Unlike existing treatments that block individual cytokines such as IL-4, IL-13 or IL-31, therapies targeting the OX40 pathway work earlier in the immune system’s response. By interrupting communication between antigen-presenting cells and T cells, they may help prevent the cycle of immune activation that drives skin inflammation.

In addition, Kwatra noted that this approach may also offer a safety advantage, since OX40L is only activated during disease flare-ups. He added that there are many OX40-targeted drugs that are already in late-stage clinical trials, bringing the field closer to potential approval and offering hope for longer-lasting relief for patients with AD and other chronic skin conditions.