Clarifying the Role of IL-13 Inhibitors in Atopic Dermatitis: Clinical Profiles, Comparisons, and Real-World Application
At the Fall Clinical 2025 session, “Illuminate the Role of IL-13 Inhibitors for the Management of Atopic Dermatitis,” Alexandra K. Golant, MD; G. Michael Lewitt, MD; and Mona Shahriari, MD, provided a focused, case-based discussion on how IL-13–targeting biologics fit into long-term atopic dermatitis (AD) care, particularly for patients with moderate-to-severe disease. The session emphasized mechanism-driven selection, real-world application, and a comparison of pivotal efficacy data for the 3 IL-13–related biologics currently available: dupilumab, lebrikizumab, and tralokinumab.
Dr Shahriari began with an overview of IL-13’s role in AD pathogenesis, highlighting its impact on itch signaling, barrier dysfunction, skin thickening, and its elevation in lesional and non-lesional skin. “IL-13 is doing a lot for our patients,” she explained. “It’s not just another cytokine—it’s chronic, it’s correlated with disease severity, and it’s elevated across ages and skin tones.”
Dr Shahriari also noted a critical mechanistic distinction between IL-13 and IL-4. “IL-4 appears in lesional skin only. IL-13 is everywhere.” As a result, blocking IL-13 may sustain inflammatory control, even when IL-4 has initiated the cascade.
The session clarified the mechanistic differences among the 3 main IL-13–targeting therapies:
- Dupilumab: Inhibits IL-4Rα, thereby blocking both IL-4 and IL-13 signaling.
- Tralokinumab: Binds directly to IL-13, preventing its interaction with its receptor.
- Lebrikizumab: Also binds IL-13, but allows receptor binding without downstream activation, thanks to high binding affinity and low dissociation rate.
This difference, Dr Shahriari emphasized, can have real-world implications in pharmacodynamics and clinical efficacy.
Dr Golant presented the case of a 17-year-old patient with long-standing AD, frequent flares, and multiple urgent care visits, each involving systemic steroids. “That’s a red flag,” she noted. “Systemic steroids are no longer considered appropriate for moderate-to-severe AD.”
The patient had tried a range of topical steroids and calcineurin inhibitors but continued to have facial and neck involvement with an Investigator’s Global Assessment (IGA)s score of 3, 15% body surface area (BSA) involvement, and an itch score of 7/10.
Recognizing the chronicity and quality-of-life impact, Dr Golant initiated lebrikizumab. At week 12, the patient had a BSA of 1%, IGA 1, and itch score of 2. “This was a beautiful response,” she said, highlighting improvement in high-impact areas like the face and neck, which are often challenging to treat.
The patient’s treatment goals were relatable: “I want to go to the beach with my girlfriend without feeling self-conscious. I hate topicals—they’ve ruined all my clothes.” Golant underscored that patient input should guide treatment conversations, especially in adolescents.
The panel reviewed IGA 0/1 (clear or almost clear) response rates across pivotal trials:
- Lebrikizumab: 33%–43%
- Tralokinumab: 15%–22%
- Dupilumab: 36%–38%
“These are deep endpoints,” Dr Golant noted, “and the lebrikizumab data show consistent skin clearance at levels comparable to dupilumab.”
They also compared itch improvement, measured by ≥4-point reduction in itch scores:
- Lebrikizumab: 38%–46%
- Tralokinumab: 20%–25%
- Dupilumab: 36%–40%
“Skin clearance isn’t enough if patients are still itchy,” Dr Golant said. “This is where lebrikizumab really shines—it hits both skin and itch.”
Reference
Golant A, Lewitt G, Shahriari M. Illuminate the role of Il-13 inhibitors for the management of atopic dermatitis. Presented at: 2025 Fall Clinical Dermatology Conference. October 23–26, 2025; Virtual.
