Lebrikizumab Shows 3-Year Sustained Efficacy in AD

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At this year’s annual American Academy of Dermatology Meeting in Orlando, Florida, Eli Lilly presented recent findings from the ADjoin long-term extension study. Researchers behind the study stated lebrikizumab (Ebglyss), an interleukin-13 (IL-13) inhibitor, demonstrated sustained efficacy and safety over 3 years in patients with moderatetosevere atopic dermatitis (AD).¹

"Health care providers are constantly searching for ways to help patients achieve deep, sustainable improvement in the signs and symptoms of their atopic dermatitis," Raj Chovatiya, MD, PhD, MSCI, clinical associate professor, Rosalind Franklin University Chicago Medical School, founder and director of the Center for Medical Dermatology + Immunology Research, said in a news release. "These 3-year data show that raising the bar in AD treatment to long-term total skin clearance was an achievable treatment goal for at least half of [lebrikizumab] week 16 responders, reinforcing its efficacy as a first-line biologic treatment for people with moderate to severe AD uncontrolled by topicals."

Mechanism of Action

Lebrikizumab selectively inhibits IL-13, a cytokine central to the pathogenesis of AD, by disrupting its signaling with high binding affinity (2,3). IL-13 contributes to the type-2 inflammatory response, leading to skin barrier dysfunction, pruritus, lichenification, and increased susceptibility to infections. By targeting IL-13, lebrikizumab mitigates these pathological mechanisms, providing significant clinical benefit to patients with moderate to severe AD.²

3-Year Clinical Efficacy

The ADjoin study evaluated long-term treatment outcomes in patients who initially responded to lebrikizumab in the ADvocate 1 and ADvocate 2 trials. Patients received a maintenance dose of 250 mg lebrikizumab either every 2 weeks or once monthly (every 4 weeks). Key efficacy endpoints included complete skin clearance (EASI 100, IGA 0), near-complete clearance (EASI 90), and durability of response.¹

Among patients receiving once-monthly lebrikizumab maintenance therapy, the study reported 50% achieved complete skin clearance (EASI 100 or IGA 0) at 3 years. Additionally, 87% maintained near-complete skin clearance (EASI 90) at3 years. Furthermore, 83% of responders did not require adjunctive topical corticosteroids or topical calcineurin inhibitors throughout the study.

Additional Subgroup Findings

ADmirable Study: This study evaluated lebrikizumab in patients with skin of color. At week 16, 58% achieved significant pruritus reduction (Pruritus NRS ≥4-point improvement), while 59% experienced notable skin pain relief (≥4-point improvement). Additionally, researchers stated over 30% reported decreased sleep disruption from itch (≥2-point improvement).

ADapt Study: This trial assessed patients previously treated with dupilumab. At week 24, researchers stated75% of patients reported significant skin pain improvement (≥4-point reduction), while 62% experienced substantial pruritus relief. Sleep interference from itch was reduced by ≥2 points in 42% of participants.

Safety Profile

The safety data from ADjoin aligned with prior phase 3 studies, with no new safety concerns emerging. Researchers stated most adverse events were mild to moderate, and treatment discontinuation due to adverse effects was infrequent. The most commonly reported adverse reactions were conjunctivitis and injection-site reactions.

Clinical Implications

The sustained efficacy of lebrikizumab over 3 years, particularly in achieving complete skin clearance, reinforces its role as a first-line biologic for moderate to severe AD inadequately controlled by topical treatments. Furthermore, the study found its once-monthly maintenance dosing offers convenience while maintaining long-term disease control. Notably, researchers stated lebrikizumab also demonstrated efficacy in patients with skin of color and those previously treated with dupilumab, broadening its clinical utility.

"We hear from patients with moderate to severe AD that they struggle with recurring and unpredictable flares and are looking for treatment options that can provide long-term disease control," Mark Genovese, MD, senior vice president of Lilly Immunology development, said in the release. "[Lebrikizumab] is the only first-line biologic treatment option for patients with disease uncontrolled by topicals to report completely clear skin at three years with a once-monthly maintenance dose. The additional assessments presented at AAD demonstrate significant improvements in disruptive symptoms, such as itch, across a range of patient groups."

Conclusion

The study found lebrikizumab provides a promising long-term treatment option for moderate to severe AD, offering deep and sustained response with a favorable safety profile. The findings from ADjoin, ADmirable, and ADapt underscore its efficacy across diverse patient populations and support its continued use in clinical practice.

References

1. Lilly's EBGLYSS® (lebrikizumab-lbkz) single monthly maintenance injection achieved completely clear skin at 3 years in half of patients with moderate-to-severe atopic dermatitis. News release. Eli Lilly. Published March 7, 2025. Accessed March 11, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-ebglyssr-lebrikizumab-lbkz-single-monthly-maintenance
2. Bernardo D, Bieber T, Torres T. Lebrikizumab for the treatment of moderate to severe atopic dermatitis. Am J Clin Dermatol. 2023 Sep;24(5):753-764. doi: 10.1007/s40257-023-00793-5. Epub 2023 Jun 2. PMID: 37266844; PMCID: PMC10460333.