Atopic Dermatitis: Investigational Anti-OX40L Antibody Shows Sustained Itch Relief, Even After Discontinuation

First author, Brian Kim, MD

Image courtesy of AAD

Amlitelimab, an investigational anti-OX40 ligand monoclonal antibody, demonstrated sustained improvement in pruritus and disease severity in adults with moderate-to-severe atopic dermatitis (AD), according to new data from the STREAM-AD Phase 2b clinical trial. Findings suggest that targeting OX40L could provide long-term symptom control, potentially shifting the treatment paradigm for AD.

The data was presented at the 2025 American Academy of Dermatology meeting being held in Orlando, Florida, from March 7-11, 2025.

The STREAM-AD trial (NCT05131477) enrolled 390 adults with moderate-to-severe AD. In part 1, participants received amlitelimab at various doses or placebo for 24 weeks. Clinical responders—those achieving at least a 75% improvement in Eczema Area and Severity Index (EASI-75) and/or an Investigator Global Assessment (IGA) score of 0/1 at week 24—entered part 2. These responders (n=190) were re-randomized in a 3:1 ratio to either withdraw from treatment or continue their pre-week 24 amlitelimab dose (250 mg with 500 mg loading dose, 250 mg, 125 mg, or 62.5 mg) or placebo for an additional 28 weeks, up to week 52.

The current post hoc analysis focused on itch response, evaluating the proportion of patients with a ≥4-point reduction from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS≥4) among clinical responders at weeks 24 and 52, according to the study abstract.

Among participants entering part 2 who received amlitelimab in part 1 (n=174), 46.6% (n=81) were PP-NRS≥4 responders at week 24. Of these, 27 continued amlitelimab treatment, and 54 withdrew during part 2, according to the abstract.

Among those who continued therapy, 74.1% maintained PP-NRS ≥ 4 response at week 52. Notably, 63.0% of patients who discontinued amlitelimab also maintained PP-NRS ≥ 4 response at week 52, suggesting a durable off-treatment effect.

These findings indicate that amlitelimab not only provides rapid symptom relief but also offers prolonged disease control even after treatment cessation. If validated in phase 3 trials, this agent could emerge as a novel therapeutic option for AD, addressing the persistent pruritus and inflammation that significantly impact patient quality of life.

The ongoing OCEANA Phase 3 program will further evaluate amlitelimab’s efficacy and safety in a broader population, including adolescents, according to the abstract.

Reference: Kim B, Kataoka Y, Blauvelt A, et al. Impact of amlitelimab (an anti-OX40 Ligand antibody) on maintenance of itch response in atopic dermatitis: results from the 52-week STREAM-AD Phase 2b study. Poster 62198. Presented at: The 2025 American Academy of Dermatology Annual Meeting. Orlando, Florida.