Tralokinumab Safe, Effective in Older Patients With AD: Post Hoc Analysis

Kate Johnson

August 31, 2023

Tralokinumab is a safe, tolerable, and effective treatment for moderate to severe atopic dermatitis (AD) in adults aged 65 years or older, according to the results of a secondary analysis of phase 3, randomized ECZTRA 1, 2, and 3 trials.

The analysis showed that more participants achieved a 75% or greater improvement in Eczema Area and Severity Index (EASI-75) and Investigator's Global Assessment (IGA) 0/1 with tralokinumab than with placebo at 16 weeks, reported Joseph F. Merola, MD, from Brigham and Women's Hospital, Harvard Medical School, Boston, and colleagues in JAMA Dermatology.

In addition, the number of patients who experienced severe adverse events (SAEs) or any AEs that led to permanent treatment discontinuation was low compared with placebo at 16 weeks. Tralokinumab (Adbry), an interleukin (IL)–13 antagonist administered subcutaneously, was approved by the US Food and Drug Administration (FDA) in December 2021 for treating moderate to severe AD in adults.

The findings are important for the older patient population who "typically face unique treatment challenges," note the authors. "Treatment for moderate-to-severe disease can be challenging, as they can experience more active and severe disease, increased comorbidity, polypharmacy, and a higher risk of infection. Other challenges include potential safety risks and low adherence to conventional therapies, like corticosteroids, phototherapy, and immunosuppressants."

The secondary analysis included a subset of 104 older patients with AD from the three trials (mean age 70-73 years), among whom, 75 were randomly assigned to treatment with tralokinumab monotherapy (n = 59; in the ECZTRA 1 and ECZTRA 2 trials) or tralokinumab plus topical corticosteroids as needed (n = 16; in the ECZRA 3 trial), and 29 to placebo. More than 56% of patients in this age group receiving tralokinumab in the three trials were taking five or more concomitant medications.

Safety data at 16 weeks was similar for both arms: Three patients in the tralokinumab group (4%) and three in the placebo arm (10.3%) experienced SAEs, with no reports of neoplasms in the placebo group and one in the tralokinumab group. 

In addition, four (5.3%) patients in the tralokinumab arm and two (6.9%) in the placebo arm experienced AEs leading to discontinuation. "No patients in the tralokinumab arm experienced vascular disorders; one patient experienced accelerated hypertension and deep vein thrombosis in the placebo group. There were no reports of herpes zoster. In addition, no deaths were reported," the authors write, adding that the overall incidence of safety events among younger patients in the trials was similar.

The proportion of patients who achieved an EASI-75 were higher for tralokinumab vs placebo-treated patients, but this only reached statistical significance for those in the ECZTRA 1 and 2 trials (33.9% vs 4.8%; P < .001). Similarly, the proportion of IGA 0/1 responders was also higher in the tralokinumab arm, but again only reached statistical significance in the first two trials (16.9% vs 0; P < .001).

A secondary efficacy endpoint was the itch Numeric Rating Scale score, which showed that the percentage of patients who achieved a reduction ≥ 4 points was higher in the tralokinumab vs placebo group in ECZTRA 1 and 2 (28.8% vs 5%) but the same in ECZTRA 3.

The authors concluded that because long-term safety and efficacy data is limited for other AD treatments in older patients, "newer targeted therapies, such as tralokinumab, might offer safer options than conventional therapies in this population, with increased risk of AEs and drug-drug interactions."

Asked to comment, Ryoji Tanei, MD, PhD, a dermatologist at the Tokyo Metropolitan Institute for Geriatrics and Gerontology in Tokyo, Japan, who specializes in AD in older populations told Medscape Medical News that tralokinumab is "very useful and highly safe" in this age group.

"It is important that, following dupilumab, another targeted-therapy for seniors with AD has been added," he said in an email, noting that the European Medicine Agency recommends Janus kinase (JAK) inhibitors only be used if there are no other suitable alternatives for this population (patients aged 65 or older with chronic inflammatory disorders) because of the risk for serious side effects, such as cardiovascular conditions and cancer. (This age group is not mentioned specifically in the FDA-required warning included in JAK inhibitor labeling.)

Tanei added that 16-week EASI-75 rates for tralokinumab seem lower than those for dupilumab, when compared with recently published pooled data from 4 randomized clinical trials of adults with moderate to severe AD aged 60 years and older. "This may be due to the involvement of systemic IL-4 activation in the pathogenesis of AD," he suggested.

Merola reported grants from LEO Pharma during the conduct of the study as well as personal fees from LEO Pharma, and consulting fees from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, and Pfizer outside the submitted work. Two authors reported being employed by LEO Pharma during the conduct of the study. One author reported personal fees from LEO Pharma during the conduct of the study, and another author reported personal fees from Target RWE and grants from Pfizer and Cosmotique Internacional SNC outside the submitted work.

No other disclosures were reported by the study authors. The study was funded by LEO Pharma.

Tanei reported no disclosures.

JAMA Dermatol. Published online August 23, 2023. Full text

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.

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