The interleukin (IL)-13 inhibitor tralokinumab (Adbry) for atopic dermatitis provided long-term disease control with a favorable safety profile and improved quality of life (QoL), data from two studies showed.
Interim results from a long-term extension study showed that 82.5% of patients had at least 75% improvement in the Eczema Area and Severity Index (EASI-75) after 2 years 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 2 years, tralokinumab was well tolerated and maintained long-term control of atopic dermatitis in adults,” the authors concluded. “The safety data reported in ECZTEND are consistent with the placebo-controlled parent trials, with adverse events occurring at lower rates. These results support the long-term, continuous use 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 first few 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 one or 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 first 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 option to enroll in ECZTEND, a 5-year extension study to assess the long-term safety and efficacy of tralokinumab.
Pooled Efficacy, Safety Data
Blauvelt and colleagues reported interim safety results for all patients enrolled in ECZTEND and efficacy data for patients who had completed 1 year of treatment in a parent trial of tralokinumab and 1 year in the extension study. The study population comprised a heterogeneous group of patients, some who had received tralokinumab since the beginning of a parent trial and others who did not receive the IL-13 inhibitor until enrolling in 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 use of tralokinumab was associated with a safety profile consistent with AEs in the parent trials. The most common AEs in the parent and extension trials were upper respiratory tract infection and atopic dermatitis. AEs leading to discontinuation occurred less frequently in the ECZTEND study.
During 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 1 year of treatment with tralokinumab. For the subgroup of patients who had an additional 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 — such as the proportion of patients with an EASI score ≤7, weekly pruritus rating, sleep interference, and QoL — were maintained during 2 years of treatment.
“This interim analysis of ECZTEND demonstrates a well-tolerated long-term safety profile and sustained efficacy in participants with up to 2 years 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 2 weeks. Participants who achieved an IGA 0/1 or EASI-75 response by 16 weeks were re-randomized to tralokinumab every 2 or 4 weeks with as-needed steroids. The post-hoc analysis included all patients initially randomized to tralokinumab, regardless of response status at 16 weeks.
The results 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 during the first 16 weeks of treatment with the IL-13 inhibitor were maintained through 32 weeks, including the eczema-related sleep interference rating scale and the Dermatology Life Quality Index (DLQI). Among patients who initially received tralokinumab every 2 weeks, 89.9% had significant improvement in at least one of the three DLQI disease domains (disease signs/activity, pruritus, and QoL) after 16 weeks, and 53.4% had clinically meaningful improvement in all 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 low in patients treated with tralokinumab compared with placebo over 32 weeks, demonstrating the [steroid]-sparing effects of tralokinumab.”
Both the 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.