IL-13 Inhibitors for Atopic Dermatitis

During his session, “Expanding Precision Treatment in Atopic Dermatitis: The Role of New and Emerging IL-13 Inhibitors,” presented at Dermatology Week 2022, Peter Lio, MD, FAAD, presented new and upcoming IL-13 inhibitors for treating atopic dermatitis (AD) by sharing their mechanisms of action and clinical data.

Regarding the mechanisms, Dr Lio showed a graph laying out the pathways of each therapeutic. He noted that when inhibitors bind to the cytokines, this kicks in and activates the JAK pathways, interacting with the nucleus and altering transcription.

He started by discussing targeted therapy, listing the following commonly used biologics:

• Dupilumab blocks at the receptor level and binds to IL-4R⍺, which blocks both IL-4 and IL-13.
• Lebrikizumab is still being studied in late-stage development but binds directly to IL-13.
• Tralokinumab, which was released at the end of last year, binds directly to IL-13.

Addressing these biologics, Dr Lio noted, “They’re interesting because they allow mother nature to make a very, very specific antibody that can bind to whatever target we want.”

With these biologics activating the JAK system, there are several different pharmaceuticals used. These include abrocitinib and upadacitinib, which are oral agents that selectively target JAK1. Ruxolitinib is another JAK inhibitor that is topical (cream-based) and targets both JAK1 and JAK2. Additionally, Dr Lio introduced baricitinib, which also targets both JAK1 and JAK2, and is in development for treating AD but has not yet been approved. Delgocitinib is also in development, but Dr Lio noted that he does not know the status of it and baricitinib as of yet.

Next, Dr Lio delved into the 3 biologics (dupilumab, tralokinumab, and lebrikizumab) in detail. Starting with dupilumab, Dr Lio noted that it has been out for some time (2017) and was initially approved for adults. However, a few years later, data supporting its use for adolescents (age 12 to 17 years) were released, and it has recently been FDA approved for patients age 6 to 11 as well. Additionally, it’s currently awaiting FDA approval for patients as young as 6 months of age because it has been proven to have the same efficacy profile as all the other age groups.

Next, Dr Lio presented tralokinumab, which was approved for adults at the end of 2021,. It is very similar to dupilumab in terms of efficacy in addition to the tolerability and safety profile issues. It is unique in that it could potentially be administered every 4 weeks, which would maintain patients on a less frequent dosing schedule.

Finally, Dr Lio shared lebrikizumab, which is an investigated agent that has yet to be FDA approved. However, he showcased recent data from a phase 2 monotherapy trial that consisted of 280 adult participants with moderate to severe AD inadequately controlled with topical corticosteroids. He shared that many of those patients achieved an Eczema Area and Severity Index score of 50/75/90 when administered 250 mg of lebrikizumab at weeks 2 and 4 compared with placebo. He also added that they had achieved an Investigator’s Global Assessment scale score of 0 or 1.

Reference
Lio P. Expanding precision treatment in atopic dermatitis: the role of new and emerging IL-13 inhibitors. Presented at: Dermatology Week 2022; May 11–14, 2022; Virtual.