Tralokinumab for Atopic Dermatitis: A Promising New Therapy

D.E. Morra; A.M. Drucker

Disclosures

The British Journal of Dermatology. 2021;184(3):86-387. 

Advances in our understanding of the pathophysiology of atopic dermatitis (AD) have led to a surge in targeted immunomodulating treatments under investigation.[1,2] In this issue of the BJD, the ECZTRA 1, 2 and 3 trials provide evidence in support of tralokinumab, a biological inhibitor of interleukin (IL)-13, as a treatment for moderate-to-severe AD.[3,4]

ECZTRA 1 and 2 were identical monotherapy trials that enrolled a combined number of 1596 adult patients with moderate-to-severe AD. Patients were randomized to subcutaneous (SC) tralokinumab 600 mg then 300 mg every 2 weeks (Q2W) or placebo. 'Monotherapy' refers to the protocol that no concomitant medications, including topical corticosteroids, were permitted in either treatment arm, except as rescue therapy. Primary endpoints were 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.[3]

The ECZTRA 3 trial enrolled 369 adult patients randomized to SC tralokinumab 300 mg Q2W or placebo, with a major difference from ECZTRA 1 and 2 being that topical corticosteroids were permitted as needed. These results are more applicable to 'real-world' use, as systemic therapies are generally used concomitantly with topical medications. The primary endpoints were the same as ECZTRA 1 and 2, and both studies also assessed the Harmonising Outcomes Measures for Eczema core outcomes: reduction in EASI, Patient-Oriented Eczema Measure, a peak pruritus numerical rating scale, and the Dermatology Life Quality Index.[3,4]

In ECZTRA 1 and 2, a significantly higher proportion of patients receiving tralokinumab achieved both primary endpoints compared with placebo. In both studies, tralokinumab led to IGA success in approximately twice as many patients as placebo (ECZTRA 1: 15·8% vs. 7·1%; ECZTRA 2: 22·2% vs. 10·9%). EASI 75 was more common with tralokinumab in ECZTRA 1 (25·0% vs. 12·7%) and ECZTRA 2 (33·2% vs. 11·4%).[3] In ECZTRA 3, response rates were higher for both tralokinumab and placebo (IGA: 38·9% vs. 26·2%; EASI 75: 56·0% vs. 35·7%), likely owing to the use of topical corticosteroids.[4] In the initial 16-week treatment period, the frequency of adverse events was similar between tralokinumab and placebo for all three studies. Conjunctivitis was an adverse event of special interest because it frequently occurs with the use of dupilumab, which also targets the IL-4/IL-13 pathway.[5] Conjunctivitis occurred more frequently in patients receiving tralokinumab in all studies, although most cases were mild or moderate.[3,4] Long-term efficacy was variable in ECZTRA 1 and 2, with approximately half of patients experiencing response maintenance at 52 weeks. Comparably, maintenance was much higher in ECZTRA 3. More research is needed to determine whether tralokinumab offers long-term superiority over other treatments.

While several AD treatments are in development, dupilumab is the only approved biological, and so is the most relevant active comparator. In our network meta-analysis (NMA), dupilumab was associated with an EASI improvement of 11·3 vs. placebo, which is higher than the EASI improvements in ECZTRA 1, 2 and 3, which ranged from 5·4 to 9·9 points.[3,4,6] These trials will be included in updates of our living NMA and will allow comparisons of tralokinumab's efficacy profile with other AD treatments.[7] Nevertheless, based on the results of these trials, tralokinumab appears to be a promising treatment option for patients with moderate-to-severe AD.

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