What Is Next for OX40 Ligand Inhibition in Atopic Dermatitis?

A recent segment of the ABCs of Dermatology podcast explored the future potential of amlitelimab in atopic dermatitis, with hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, emphasizing the importance of maintaining scientific curiosity and clinical perspective as more data emerge regarding OX40 ligand-targeted therapy.

The discussion centered on balancing enthusiasm for a novel therapeutic mechanism with the need for continued investigation into safety signals and patient selection. Bunick argued the field should remain optimistic about amlitelimab’s future, noting that a better understanding of patient-specific risk factors could ultimately help clinicians identify individuals most appropriate for treatment. He compared this approach to the risk stratification strategies dermatologists have already adopted for JAK inhibitors, where clinicians routinely evaluate patients for factors that may increase the likelihood of adverse events before initiating therapy.

Rather than viewing emerging questions about the therapy as a reason to abandon the pathway, Bunick suggested that dermatology should focus on generating more data and demanding greater scientific transparency. In his view, understanding the underlying biology behind observed safety findings will allow clinicians to make more informed, patient-centered decisions while preserving access to potentially valuable treatment options.

Ackerman agreed, describing the OX40-OX40 ligand pathway as an example of why dermatology remains one of the most rapidly evolving areas of medicine. She highlighted the complexity of inflammatory disease biology and suggested that upstream immune modulation may ultimately have implications extending beyond atopic dermatitis. According to Ackerman, the pathway’s broad immunologic relevance could make it important not only for eczema but also for other chronic inflammatory disorders that continue to present therapeutic challenges.

The hosts also discussed the ongoing unmet need in atopic dermatitis despite an expanding therapeutic landscape. Ackerman noted that the disease remains highly heterogeneous, with significant variability in clinical presentation and treatment response. As a result, she argued that continued investment in new mechanisms of action remains essential, even as effective therapies already exist. She pointed to the continued development of amlitelimab as evidence of an ongoing commitment to addressing gaps in care for patients whose disease remains difficult to control.

The conversation then shifted to Ackerman’s firsthand experience as a clinical trial investigator. Drawing on her participation in amlitelimab studies, Ackerman described seeing several patients achieve substantial improvements despite having previously failed multiple therapies. Although she acknowledged that these observations represent only a small number of patients, she noted that some individuals continued to do well even after completing the interventional portion of the study. Ackerman said she had anticipated needing to rapidly transition certain participants to additional treatments after trial completion because of the severity and recalcitrance of their disease, but some had yet to experience significant flares.

Bunick cautioned against drawing broad conclusions from individual cases but viewed those experiences as further reason to remain open-minded. Both hosts ultimately stressed that advancing patient care requires careful scientific investigation, patience, and a willingness to evaluate new therapeutic pathways on the basis of evolving evidence. They concluded that maintaining a patient-centered approach while pursuing deeper mechanistic understanding will be critical as the role of OX40 ligand inhibition continues to develop within atopic dermatitis and potentially other inflammatory diseases.

Editor’s note: This segment was summarized with the help of AI tools.

Relevant disclosures for Bunick include AbbVie, South Beach Symposium, Almirall, Apogee Therapeutics, Arcutis Biotherapeutics, Daiichi Sankyo, Eli Lilly, LEO Pharma, US, Novan, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Timber Pharmaceuticals, and UCB. Relevant disclosures for Ackerman include AbbVie, Alumis, Amgen, Arcutis, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, L'Oréal, Novartis, Sun Pharmaceutical, and UCB.

References

1. Sanofi. Press Release: AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Sanofi.com. Published March 28, 2026. Accessed June 1, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-03-28-15-00-00-3264184.

2. Kyowa Kirin. Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials - Kyowa Kirin. Kyowakirin.com. Published March 3, 2026. Accessed June 1, 2026. https://www.kyowakirin.com/media_center/news_releases/2026/e20260303_01.html.