Advances in the understanding of the pathophysiology of atopic dermatitis (AD) have led to an increase in immunomodulating treatments under investigation, according to commentary published in the British Journal of Dermatology.1

The ECZTRA 1, 2, and 3 trials have recently found that tralokinumab, a biologic inhibitor of interleukin (IL)-13, is beneficial for patients with moderate to severe AD.

Wollenberg et al reported on ECZTRA 1 and 2, which were monotherapy trials that included a total of 1596 adult patients with moderate to severe AD.2 Silverberg et al reported on ECZTRA 3, which enrolled 369 adult patients.3 In ECZTRA 3, topical corticosteroids were permitted as needed. Primary endpoints were the same in all 3 trials—an Investigator’s Global Assessment (IGA) score of 0 or 1, and 75% improvement in Eczema Area and Severity Index (EASI 75) at 16 weeks.


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ECZTRA 1 and 2 found that a significantly higher percentage of patients who received tralokinumab achieved both primary endpoints compared with those who received placebo. Tralokinumab led to IGA success in about twice as many patients compared with placebo (ECZTRA 1: 15.8% vs 7.1%; ECZTRA 2: 22.2% vs 10.9%). EASI 75 was more frequent with tralokinumab in ECZTRA 1 (25.0% vs 12.7%) and ECZTRA 2 (33.2% vs 11.4%).

In ECZTRA 3, the response rates were higher for tralokinumab and placebo (IGA: 38.9% vs 26.2%; EASI 75: 56.0% vs 35.7%), “likely owing to the use of topical corticosteroids,” according to the commentary authors.

Dupilumab is the only currently approved biologic therapy and is “the most relevant active comparator,” according to Drucker et al, who compared the effectiveness and safety of systemic immunomodulatory treatments in patients with atopic dermatitis in a systematic review and network meta-analysis.4

“In our network meta-analysis (NMA), dupilumab was associated with an EASI improvement of 11.3 versus placebo, which is higher than the EASI improvements in ECZTRA 1, 2 and 3, which ranged from 5.4 to 9.9 points,” the authors stated.1

Cyclosporine and dupilumab were similarly effective compared with placebo in clearing clinical signs of atopic dermatitis and may be superior to methotrexate and azathioprine, they noted.4

“These trials will be included in updates of our living NMA and will allow comparisons of tralokinumab’s efficacy profile with other AD treatments,” the commentary authors concluded. “Nevertheless, based on the results of these trials, tralokinumab appears to be a promising treatment option for patients with moderate-to-severe AD.”1

Disclosures: One of the commentary authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

References

1. Morra DE, Drucker AM. Tralokinumab for atopic dermatitis: a promising new therapy. Published online December 21, 2020. Br J Dermatol. doi:10.1111/bjd.19699

2. Wollenberg A, Blauvelt A, Guttman-Yassky E, et al; ECZTRA 1 and ECZTRA 2 study investigators. Tralokinumab for moderate‐to‐severe atopic dermatitis: results from two 52‐week, randomized, double‐blind, multicentre, placebo‐controlled phase III trials (ECZTRA 1 and ECZTRA 2. Published online September 30, 2020. Br J Dermatol. doi:10.1111/bjd.19574

3. Silverberg JI, Toth D, Bieber T, et al. Tralokinumab plus topical corticosteroids for the treatment of moderate‐to‐severe atopic dermatitis: results from the double‐blind, randomized, multicentre, placebo‐controlled phase III ECZTRA 3 trial. Published online September 30, 2020. Br J Dermatol. doi:10.1111/bjd.19573

4. Drucker AM, Ellis AG, Bohdanowicz M, et al. Systemic immunomodulatory treatments for patients with atopic dermatitis: a systematic review and network meta-analysis. JAMA Dermatol. 2020;156(6):659-667. doi:10.1001/jamadermatol.2020.0796