Mona Shahriari, MD, FAAD, on OX40-Targeted Therapy in AD

Atopic dermatitis (AD) management has evolved considerably over the past decade, yet substantial unmet needs remain. In an interview with Dermatology Times at South Beach Symposium 2026, Mona Shahriari, MD, FAAD, associate clinical professor of dermatology at Yale University and associate director of clinical trials at CCD Research, highlighted emerging strategies that may redefine therapeutic expectations for patients with moderate to severe AD.

Historically, AD therapies have focused on suppressing symptoms of the condition. As Shahriari notes, “Up until now, we've really focused on our different therapeutics in AD, suppressing the flares and the inflammation. But wouldn't it be great if we could retrain or rebalance our immune system?” Despite the current arsenal, including cytokine-specific biologics and JAK inhibitors, a subset of patients continues to demonstrate suboptimal responses, reflecting the heterogeneity of disease phenotypes and endotypes.

One promising avenue involves targeting the OX40 pathway, which modulates antigen-specific T cells upstream of cytokine production. Unlike conventional therapies, which act at the level of cytokines or downstream T cells, OX40-directed treatments aim to address the root immune dysfunction. As Shahriari explains, “When you're thinking of OX40, you're going above the level of the cytokines, above the level of the T cells that make those cytokines, and targeting that antigen-specific T cell directly, so you're getting to the root of the problem.” This upstream targeting may prevent formation of pathogenic memory T cells, potentially offering durable off-drug remission.

Late-stage investigational therapies, including rocatinlimab and amlitamab, have demonstrated encouraging results in phase 2 trials. Rocatinlimab maintained EASI-75 responses for up to 20 weeks post-treatment, with over 90% of patients at higher doses sustaining these improvements. Similarly, amlitamab showed sustained efficacy at week 52, independent of continued dosing. Shahriari remarks, “Whether you stayed on your dose or the drug was gone, at week 52, we actually had patients maintain similar efficacy.” These findings suggest the potential for long-term disease control beyond active therapy.

Safety profiles thus far appear manageable. Rocatinlimab is primarily associated with transient pyrexia after the first injection, while amlitamab’s adverse events are comparable to placebo over 24 weeks. Nevertheless, Shahriari emphasizes the need for continued vigilance: “Anytime I have a new mechanism, I'm gonna be a little bit more concerned, and I wanna see longer-term data.”

Target populations for OX40-targeted therapy may include patients with heterogeneous disease or those seeking durable off-drug remission. However, due to the gradual onset of effect, these therapies may be less suitable for patients requiring rapid disease control. Future developments, such as bispecific constructs combining IL-13 inhibition with OX40 blockade, aim to optimize both speed and longevity of response.

Overall, these emerging immunomodulatory strategies represent a paradigm shift in AD treatment, moving beyond symptomatic control toward potential immune rebalancing and sustained disease remission. Further phase 3 data will bring more answers for clinicians interested in this therapy for their patients.