Looking Ahead: Potential Uses and Unknowns for OX40 Pathway–Targeted Therapies in Atopic Dermatitis

Video content above is prompted by the following: Determining the optimal positioning of OX40-pathway therapies within the current atopic dermatitis treatment algorithm presents significant challenges given the expanding therapeutic options and varying patient responses to existing biologics and JAK inhibitors. Dr Eichenfield notes the complexity of treatment selection, where patients may fail one highly effective therapy yet respond dramatically to another, highlighting the unpredictable nature of individual treatment responses. The potential for profound long-term effects with OX40 targeting could justify first-line positioning after topicals, but the slower onset of action compared with that of current biologics creates a therapeutic trade-off requiring careful consideration.

OX40-pathway therapies appear to offer a distinct therapeutic profile emphasizing durability over rapid response, contrasting with current biologics and oral therapies that provide faster symptom relief. The upstream targeting approach requires more immunologic steps to achieve clinical effects, potentially resulting in slower onset but offering the possibility of sustained responses with extended dosing intervals or even treatment discontinuation. This trade-off between immediate symptom control and long-term disease modification may influence treatment positioning based on patient priorities, disease severity, and previous treatment history.

Key outstanding questions include comprehensive safety profiles with larger patient populations, duration of therapeutic effects, and development of predictive biomarkers or phenotypic factors to identify optimal candidates for each therapy. Dr Eichenfield emphasizes the need for tools to predict which patients will achieve high-level responses, as current cytokine profiling approaches may not apply to OX40-pathway targeting. The dynamic nature of current drug development timelines suggests that definitive answers regarding optimal patient selection, safety profiles, and treatment positioning will emerge within the next year, fundamentally shaping future clinical practice approaches to atopic dermatitis management.