In this lively and deeply informative episode of The Spot Check, host Jamie Restivo, MPAS, PA-C, sits down with Benjamin Lockshin, MD, dermatologist and Director of the Clinical Trials Center at U.S. Dermatology Partners, to unpack one of the most promising frontiers in atopic dermatitis (AD): targeting the OX40–OX40 ligand pathway.  Together, they review the AD treatment landscape and current gaps in therapies. Lockshin outlines the promise of OX40 inhibition as a potential step toward true disease modification, with less frequent dosing and durable remission that could reshape long-term disease management.  Restivo and Lockshin walk listeners through the immunologic mechanisms at play, breaking down how OX40 and its ligand function as upstream co-stimulatory molecules driving inflammation, barrier dysfunction, and itch. They compare emerging agents rocatinlimab and amlitelimab, explaining how each targets a different side of the OX40 pathway, and discuss early data showing high EASI-90 to EASI-100 responses and sustained clearance even after treatment withdrawal.  Their conversation delves into what makes these agents distinct from JAK inhibitors and biologics, emphasizing that OX40 inhibition appears to rebalance rather than deplete T cells, with minimal immunosuppression and a favorable safety profile so far. Lockshin shares practical considerations around patient selection, dosing convenience, and future applications beyond AD—including prurigo nodularis, alopecia areata, and potential oncologic uses.  The discussion closes on a forward-looking note: OX40 may be dermatology’s first real leap toward immune reprogramming. As Lockshin puts it, “good things are worth the wait,” and OX40 inhibition could mark the next chapter in changing the course–not just the symptoms—of atopic dermatitis.