Expanding Role of IL-13–Targeted Biologics for Atopic Dermatitis

At the 2025 Fall Clinical Dermatology Conference in Las Vegas, Nevada, Mona Shahriari, MD, outlined how advances in cytokine understanding continue to refine the treatment of atopic dermatitis (AD).¹ Shahriari, assistant clinical professor of dermatology at Yale School of Medicine and associate director of clinical trials at Central Connecticut Dermatology Research, emphasized that AD is increasingly recognized as an IL-13–dominant disease, positioning IL-13 inhibition as a cornerstone of targeted therapy for patients across all ages and disease severities.

IL-13 as a Central Driver of AD Pathophysiology

“IL-13 is not just another proinflammatory cytokine. It actually does a lot in our body,” Shahriari explained. It is expressed in both lesional and nonlesional skin and contributes to multiple features of AD, including chronic inflammation, skin barrier dysfunction, and pruritus. Importantly, IL-13 is found in patients across diverse skin tones and throughout the lifespan, from infancy to adulthood.

Given its role in disease persistence and itch, Shahriari noted that direct IL-13 inhibition represents an important therapeutic strategy. Three biologics have become central to this discussion: dupilumab, which blocks the IL-4 receptor alpha (thereby inhibiting both IL-4 and IL-13 signaling), and tralokinumab and lebrikizumab, which specifically target IL-13 itself.

Although tralokinumab and lebrikizumab share a similar mechanism of cytokine blockade, their molecular binding profiles differ. “Lebrikizumab latches onto the IL-13 molecule more intensely with a higher affinity and lower dissociation rate—it doesn’t want to let go,” she said, highlighting subtle pharmacologic distinctions that may translate to clinical nuance.

Case-Based Insights and High-Impact Sites

Shahriari presented case-based examples to illustrate how IL-13–targeted agents are applied in real-world settings. In one case, an adolescent with head and neck–predominant AD achieved meaningful improvement after 12 weeks of lebrikizumab, particularly appreciating its every 4-week dosing schedule. She noted that for patients with head and neck involvement, where dupilumab-associated flares are a concern, IL-13–specific inhibition may offer an alternative with favorable tolerability.

She also emphasized that disease burden should not be measured solely by body surface area (BSA). “Just because the AD is not taking up a huge BSA, such as on the face, hands, or feet, it can still be very troubling to patients,” she said. According to Shahriari, data from IL-13 inhibitor studies demonstrate significant efficacy in these high-impact areas, regardless of overall BSA, offering clinicians flexibility in tailoring therapy to patient needs.

Switching and Sequencing in the Biologic Era

Therapy selection and sequencing remain critical considerations. “If somebody is doing well on a drug and they wake up one day and now they're not, or maybe they're having an adverse event, what does that conversation look like? What is the nuance of changing therapy?” Shahriari explained. For patients with inadequate response or adverse events on dupilumab, such as conjunctivitis or facial erythema, transitioning to an IL-13–specific inhibitor or a JAK inhibitor can be effective.

Findings from the ADAPT trial (NCT05369403) reinforce this: patients who discontinued dupilumab due to eye symptoms, arthralgias, or facial redness did not experience recurrence of those effects after switching to lebrikizumab.² “It gives us hope that no matter what your patient is struggling with, whether they're doing well from the get-go, or they're partly through their treatment course and they're an experienced systemic patient, there's a lot that IL-13 inhibition can offer our patients,” Shahriari concluded.

References

1. Golant A, Lewitt GM, Shahriari M. Illuminate the role of IL-13 inhibitors for the management of atopic dermatitis. Presented: 2025 Fall Clinical Dermatology Conference; October 23-26, 2025; Las Vegas, NV.
2. A study of lebrikizumab (LY3650150) in adult and adolescent participants with moderate-to-severe atopic dermatitis previously treated with dupilumab (ADapt). ClinicalTrials.gov. Updated March 19, 2025. Accessed October 26, 2025. https://www.clinicaltrials.gov/study/NCT05369403