ATOPIC dermatitis (AD) is the most common chronic inflammatory skin condition, affecting up to 10% of adults and up to 20% of children globally. The clinical manifestations of AD are diverse, varying in intensity and distribution, and are driven by a complex network of immune pathways that contribute to inflammation. While T helper (Th) 2 cells and their associated cytokines, such as interleukin (IL)-4, IL-13, and IL-31, have been identified as central mediators of the disease, research has revealed the involvement of other T-cell subsets, including Th1, Th17, and Th22 cells, along with cytokines like interferon (IFN)γ and IL-17, in the pathogenesis of AD.
Advances in understanding AD’s underlying mechanisms have led to expanded treatment options, especially for patients with moderate-to-severe forms of the disease. Biologics targeting IL-4 and IL-13, as well as Janus kinase (JAK) inhibitors, have shown promise. Dupilumab, a biologic that blocks the IL-4 receptor, is often the first treatment option for patients, although it has limitations in terms of efficacy and long-term outcomes. In some studies, up to 45% of patients receiving systemic therapies, including dupilumab, experienced non-response, which could include the need for treatment modifications or hospital visits for complications like infections.
JAK inhibitors, which target the JAK-STAT pathway, have also been effective but are associated with an increased risk of adverse events, particularly with prolonged use. As AD remains a multifactorial disease, there is an ongoing need for treatments that can target multiple immune pathways with improved safety and durability.
Rocatinlimab, a novel therapy targeting the OX40 pathway, shows potential as an alternative treatment. The OX40 pathway is crucial in T-cell activation and is involved in the pathogenesis of AD. By blocking the OX40 receptor, rocatinlimab may inhibit antigen-specific T cells that produce pro-inflammatory cytokines, such as IL-4 and IL-13, without causing generalized immunosuppression. The early clinical trials have shown promising results, with significant improvements in disease scores and sustained efficacy after treatment cessation. As of 2024, the ROCKET phase 3 program, which is evaluating rocatinlimab in over 3,100 patients globally, is assessing its efficacy and long-term safety. The program aims to set a new benchmark in AD treatment, offering the potential for more durable responses and fewer side effects compared to current therapies.
Reference
Guttman-Yassky E et al. ROCKET: a phase 3 program evaluating the efficacy and safety of rocatinlimab in moderate-to-severe atopic dermatitis. Immunotherapy. 2025;17(2):83-94.
