Amlitelimab Improves QoL and Disease Control in AD

Image Credit: © DermNet

The impact of atopic dermatitis (AD) extends beyond visible signs, with patients frequently experiencing disrupted sleep, anxiety, depression, and decreased quality of life. Despite several effective therapies, long-term disease control and sustained patient relief remain unmet needs in moderate to severe AD management.¹

"The OX40 signaling pathway, which consists of OX40 ligand (OX40L) and the OX40 receptor (OX40), represents an exciting new target for atopic dermatitis therapy. These data show that amlitelimab, a biologic therapy that blocks OX40L, was associated with clinically meaningful improvement in multiple clinician and patient reported outcome assessments at 24 weeks," Raj Chovatiya, MD, PhD, MSCI, clinical associate professor at the Rosalind Franklin University Chicago Medical School, founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, and a Dermatology Times Editorial Advisory Board member, told Dermatology Times. "Even more exciting was the maintenance of response in these outcomes for an additional 28 weeks among patients who discontinued therapy, which suggests some unique features and potential advantages that may come with this mechanism of action."

Traditional clinical assessments, such as the Eczema Area and Severity Index (EASI), have been foundational in measuring AD severity. However, EASI and other clinician-reported outcomes (ClinROs) like SCORing Atopic Dermatitis (SCORAD) and body surface area (BSA) involvement primarily evaluate observable signs, often overlooking the lived patient experience. In contrast, patient-reported outcomes (PROs), including the Dermatology Life Quality Index (DLQI), the Patient-Oriented Eczema Measure (POEM), and the Atopic Dermatitis Control Tool (ADCT), provide essential insights into symptom severity, quality of life, and disease control from the patient’s perspective.²

The phase 2b STREAM-AD trial (NCT05131477) evaluated amlitelimab, a fully human, nondepleting anti-OX40L monoclonal antibody, in adults with moderate to severe AD. Amlitelimab acts by inhibiting OX40L on antigen-presenting cells, thereby reducing T-cell-mediated inflammation without depleting immune cells. The trial's primary analysis demonstrated significant reductions in EASI scores, but a subsequent post hoc analysis focused on both ClinROs and PROs to assess broader efficacy.^3-4

Trial Design and Clinical Assessments

STREAM-AD was a 2 part study involving 390 adults randomized to receive 1 of 4 amlitelimab dosing regimens or placebo for 24 weeks (part 1). Clinical responders—defined as those achieving an Investigator Global Assessment (IGA) score of 0/1 and/or 75% EASI improvement (EASI-75)—were rerandomized in part 2 to continue amlitelimab or receive placebo for an additional28 weeks. ClinROs (SCORAD, BSA) and PROs (DLQI, POEM, ADCT) were evaluated from baseline to week 24 and again at week 52 to assess maintenance of response.

Meaningful clinical changes were predefined: ≥8.7-point SCORAD reduction (with baseline ≥8.7), ≥4-point improvements in POEM or DLQI (baseline ≥4), and ADCT scores <7. These thresholds allowed evaluation of both the depth and durability of patient response.

Results and Clinical Relevance

By week 24, researchers found patients treated with amlitelimab experienced significant and early improvements in all outcome measures. Improvements in SCORAD and BSA were seen as early as week 8. POEM improvements appeared by week 4 in several treatment arms, and DLQI improvement was seen as early as week 2 in the highest-dose group. ADCT scores also showed significant reductions by week 16. The study stated tese findings were consistent across both WOCF and as-observed statistical methods.

Among week 24 clinical responders, researchers stated the majority achieved meaningful clinical improvements across COAs: 86.8% (SCORAD), 75.9% (POEM), 75.3% (DLQI), and 58.0% (ADCT). Notably, improvements were maintained at week 52 in both treatment continuation and withdrawal groups. For those continuing amlitelimab, maintenance rates were 82.9% (SCORAD), 83.3% (POEM), 86.8% (DLQI), and 77.4% (ADCT). Even after treatment withdrawal, substantial proportions maintained clinical benefit—demonstrating the potential for durable, off-therapy disease control.

Implications for Clinical Practice

This analysis underscores amlitelimab’s therapeutic potential not only in reducing visible signs of AD but also in improving and sustaining patient-reported quality of life and disease control. Unlike some current treatments, which may require continuous use to maintain effect, amlitelimab's ability to sustain improvements post-treatment may offer a more flexible, patient-centered treatment paradigm.

The data also reinforce the importance of incorporating PROs into clinical trial design and practice. While ClinROs remain valuable for assessing objective signs, PROs reveal treatment impact on patient functioning and well-being—critical factors in determining therapeutic success.

Limitations and Future Directions

While promising, the study’s population primarily included adults of central European descent, limiting generalizability to broader populations. Additionally, although validated, the COAs used do not fully capture long-term disease variability. As more therapies aim for remission or intermittent dosing, standardized definitions of long-term control in AD are needed.

Phase 3 OCEANA trials are underway to confirm these findings in a more diverse cohort and evaluate extended dosing intervals, including 12-week regimens.

Conclusion

The study found amlitelimab demonstrated robust and sustained improvements in clinician- and patient-reported outcomes in adults with moderate to severe AD. The STREAM-AD trial provides preliminary evidence supporting OX40L blockade as a viable strategy for long-term control of AD with potential for reduced treatment burden. Incorporating both ClinROs and PROs offers a more holistic understanding of therapeutic benefit and aligns clinical success with patient priorities.

References

1. Wollenberg A, Gooderham M, Katoh N, et al. Patient-reported burden in adults with atopic dermatitis: an international qualitative study. Arch Dermatol Res. 2024;316(7):380. Published 2024 Jun 8. doi:10.1007/s00403-024-03130-w
2. Chopra R, Vakharia PP, Sacotte R, et al. Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring Atopic Dermatitis (SCORAD), objective SCORAD, Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis. Br J Dermatol. 2017;177(5):1316-1321. doi:10.1111/bjd.15641
3. Weidinger S, Blauvelt A, Papp KA, et al. Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate to severe atopic dermatitis. J Allergy Clin Immunol. 2025;155(4):1264-1275. doi:10.1016/j.jaci.2024.10.031
4. Blauvelt A, Chovatiya R, Merola JF, et al. Improvement and maintenance of clinical outcome assessments in atopic dermatitis with amlitelimab. J EurAcad Dermatol Venereol. Published online July 24, 2025. doi:10.1111/jdv.20877