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Durable Responses, Safety in Atopic Dermatitis Treated With IL-13 Inhibitor

The interleukin (IL)-13 inhibitor tralokinumab (Adbry) for atopic dermatitis provided long-term disease control with a good safety profile and improved standard of living (QoL), data from two studies showed.

Interim results from the long-term extension study showed that 82.5% of patients had at the very least 75% improvement in the Eczema Area and Severity Index (EASI-75) after 24 months of follow-up. No new or unexpected adverse events (AEs) occurred in tralokinumab-treated patients, reported Andrew Blauvelt, MD, of the Oregon Medical Research Center in Portland, and co-authors in the Journal of the American Academy of Dermatology.

“Over 24 months, tralokinumab was well tolerated and maintained long-term control of atopic dermatitis in adults,” the authors concluded. “The safety data reported in ECZTEND are in keeping with the placebo-controlled parent trials, with adverse events occurring at lower rates. These results support the long-term, continuous usage of tralokinumab in adults with moderate-to-severe atopic dermatitis.”

A post-hoc analysis of a 32-week study of tralokinumab plus topical corticosteroids showed that patient-reported outcomes (PROs) improved within the initial couple of weeks of treatment and were sustained. After 32 weeks, 70.8% of patients reported improved sleep, and 66.8% had overall improvement in QoL. Almost 90% of patients had clinically meaningful improvement in a single or even more QoL domains, reported Jonathan I. Silverberg, MD, of George Washington University in Washington, D.C., and co-authors in the American Journal of Clinical Dermatology.

The initial IL-13-specific therapy approved for atopic dermatitis, tralokinumab was evaluated in multiple phase II and phase III trials of patients with moderate-to-severe atopic dermatitis. Participants in those trials had the choice to sign up in ECZTEND, a 5-year extension study to measure the long-term safety and efficacy of tralokinumab.

Pooled Efficacy, Safety Data

Blauvelt and colleagues reported interim safety results for several patients signed up for ECZTEND and efficacy data for patients who had completed 12 months of treatment in a parent trial of tralokinumab and 12 months in the extension study. The analysis population comprised a heterogeneous band of patients, some who had received tralokinumab because the beginning of a parent trial among others who didn’t have the IL-13 inhibitor until searching for ECZTEND.

The 2-year efficacy analysis included 345 patients with even distribution of moderate or severe atopic dermatitis by Investigator Global Assessment (IGA) at the baseline of the parent trials. At the ECZTEND baseline, 30.4% of patients had moderate disease activity and 5.8% had severe disease activity. Median EASI score was 26.7 at the parent trials’ baseline and 4.7 at enrollment in ECZTEND.

The safety analysis included 1,174 patients treated for 1,235.7 patient-years. Long-term usage of tralokinumab was of a safety profile in keeping with AEs in the parent trials. The most typical AEs in the parent and extension trials were upper respiratory system infection and atopic dermatitis. AEs resulting in discontinuation occurred less frequently in the ECZTEND study.

Through the parent trials, 82.8% of 612 patients met EASI-75 response criteria, 61.0% met EASI-90 criteria, and 49.7% had IGA scores of 0/1 (clear/almost clear) after 12 months of treatment with tralokinumab. For the subgroup of patients who had yet another year of treatment in the ECZTEND study (n=345), response rates were 82.5% for EASI-75, 59.8% for EASI-90, and 48.1% for IGA 0/1. Median EASI improvement for the 2-year subgroup was 88.0%.

Improvements in other outcomes — like the proportion of patients having an EASI score 7, weekly pruritus rating, sleep interference, and QoL — were maintained during 24 months of treatment.

“This interim analysis of ECZTEND demonstrates a well-tolerated long-term safety profile and sustained efficacy in participants with around 24 months of tralokinumab treatment,” Blauvelt and co-authors concluded. “These data support specific inhibition of IL-13 with tralokinumab as a safe and efficacious option for the long-term treatment of moderate-to-severe atopic dermatitis.”

32-Week Randomized Trial

Silverberg and colleagues reported on the impact of tralokinumab plus as-needed topical corticosteroids on atopic dermatitis severity and health-related QoL over a 32-week period in the randomized phase III ECZTRA 3 trial. Patients were initially randomized to tralokinumab or placebo every 14 days. Participants who achieved an IGA 0/1 or EASI-75 response by 16 weeks were re-randomized to tralokinumab every 2 or four weeks with as-needed steroids. The post-hoc analysis included all patients initially randomized to tralokinumab, irrespective of response status at 16 weeks.

The outcomes showed an EASI-75 response rate of 70.2% in patients who received tralokinumab after week 16, and 50.4% of patients met EASI-90 response criteria.

Improvement in PROs through the first 16 weeks of treatment with the IL-13 inhibitor were maintained through 32 weeks, like the eczema-related sleep interference rating scale and the Dermatology Life Quality Index (DLQI). Among patients who initially received tralokinumab every 14 days, 89.9% had significant improvement in a minumum of one of the three DLQI disease domains (disease signs/activity, pruritus, and QoL) after 16 weeks, and 53.4% had clinically meaningful improvement in every three domains versus placebo (P<0.001).

“Tralokinumab plus topical corticosteroids as needed provided progressive and sustained improvements over 32 weeks in the extent and severity of atopic dermatitis and in patient-reported outcomes in patients with moderate-to-severe atopic dermatitis,” Silverberg and co-authors concluded. “Topical corticosteroid use, as needed, remained lower in patients treated with tralokinumab weighed against placebo over 32 weeks, demonstrating the [steroid]-sparing ramifications of tralokinumab.”

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    Charles Bankhead is senior editor for oncology and in addition covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures

Both ECZTEND and ECZTRA 3 studies were supported by LEO Pharma.

Blauvelt disclosed relationships with AbbVie, Abcentra, ALIGOS, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi/Genzyme, Sun Pharma, UCB Pharma, and Vibliome.

Silverberg disclosed relationships with AbbVie, Afyx, AnaptysBio, Arcutis, Arena, Asana, Aslan, BiomX, Bluefin, Bodewell, Boehringer Ingelheim, Celgene, Connect Biopharma, Dermavant, Dermira, DS Biopharma, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Kymab, LEO Pharma, Luna, Menlo, Novartis, RAPT, Realm, Regeneron, and Sanofi/Genzyme.

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