Joseph F. Merola, MD, MMSc

Credit: brighamandwomens.org

Tralokinumab is both effective and well-tolerated in individuals who are 65 years or older and have moderate-to-severe atopic dermatitis (AD), according to recent findings.¹

The new findings resulted from recent research assessing tralokinumab—a high-affinity monoclonal antibody which targets interleukin (IL)-13—following prior data indicating its association with substantial improvements in both Eczema Area and Severity Index (EASI) and Investigator’s Global Assessment (IGA) scores.^2,3

This new study’s investigators conducted a post-hoc analysis for adults who are in an older subpopulation, and the research was authored by Joseph F. Merola, MD, MMSc, from Brigham and Women’s Hospital at Harvard Medical School in Boston.

“The objective of this subgroup analysis of the ECZTRA 1, 2, and 3 trials was to evaluate the safety and efficacy of tralokinumab in adults 65 years or older with moderate-to-severe AD,” Merola and colleagues wrote.

Background and Findings

The investigators’ post-hoc analysis examined the results of the ECZTRA 1, 2, and 3 studies, which had previously been published. In ECZTRA 1 and 2, investigators had found that tralokinumab monotherapy was shown to be superior to the placebo at Week 16, in addition to being well-tolerated up to 52 weeks into their treatment.

In ECZTRA 3, the treatment at a dose of 300 mg and combined with topical corticosteroids as necessary was both efficacious and well-tolerated in those with moderate‐to‐severe AD. Each of these results led to the current post-hoc analysis.

During this post-hoc analysis, patients were separated into 3 distinct age ranges: 18 - 49 years, 50 - 64 years, and 65 years or older; however, the team’s randomization did not take age categories into consideration.

The research team’s sensitivity analyses were carried out through the use of the population reflected in the tralokinumab US prescribing information, termed the ‘USPI population.’ The safety outcomes they assessed would cover discontinuations of tralokinumab, the rates of study participants reporting experiences of 1 or more adverse events (AEs) at Week 16.

These AEs included AEs of special interest or ‘AESI,’ treatment-emergent AEs that had a focus on cardiovascular effects, and serious AEs or ‘SAEs.’ The team noted that their primary efficacy endpoints were made to include the amount of individuals reporting an IGA score of 0 or of 1 as well as those reaching a minimum of 75% improvement in EASI-75 at Week 16.

One of the major secondary efficacy endpoints decided upon by the investigators was participant Numeric Rating Scale (NRS) itch score of 4 or greater at Week 16.

The research team’s analysis covered a group of 75-and-older adults—56% of which were women—who had been given tralokinumab treatment during the ECZTRA 1, 2, and 3 trials. Comparable numbers of participants noted AEs in both the treatment and placebo arms, with rates of 58% versus 58%, respectively.

AEs considered to be severe were found by the team to have been experienced by 4% of participants in the treatment arm and 10.3% in the placebo arm, with AE-related discontinuations having occurred in 5.3% and 6.9%, respectively. The treatment group reported a higher number of individuals reaching a 75% or greater improvement in EASI scores versus the placebo group, with 33.9% versus 4.8% (P < .001), respectively, in ECZTRA 1 and 2.

Similar trends, though they were shown to be statistically insignificant, were observed by the investigators in the ECZTRA 3 trial. Both safety as well as efficacy outcomes among the study’s older population were shown to be comparable to the younger participant cohorts, although the limited sample size precluded broad generalizations from the team’s analysis.

“More older adults achieved EASI-75 and IGA 0/1 with tralokinumab than with placebo,” they wrote. “These findings suggest that tralokinumab is safe and effective in those 65 years or older with moderate-to-severe AD.”

References

1. ^{Merola JF, Butler DC, Mark T, Schneider S, Kim Y, Abuabara K. Safety and Efficacy of Tralokinumab in Older Adults With Moderate-to-Severe Atopic Dermatitis: A Secondary Analysis. JAMA Dermatol. Published online August 23, 2023. doi:10.1001/jamadermatol.2023.2626.}
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). Br J Dermatol. 2021;184(3):437-449. doi:10.1111/bjd.19574.}
3. ^{Tsoi LC, Rodriguez E, Degenhardt F, et al. Atopic dermatitis is an IL-13–dominant disease with greater molecular heterogeneity compared to psoriasis. J Invest Dermatol. 2019;139(7):1480-1489. doi:10.1016/j.jid.2018.12.018.}