Data from two studies show that the interleukin (IL)-13 inhibitor tralokinumab (Adbry) for the treatment of atopic dermatitis provides a favorable safety profile and improved quality of life (QoL ) for long-term disease control.
Interim results from a long-term extension study showed at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) in 82.5% of patients after 2 years of follow-up— up. No new or unexpected adverse events (AEs) occurred in patients treated with tralokinumab dermatology .
“Tralokinumab was well tolerated and long-term controlled atopic dermatitis in adults over 2 years,” the authors concluded. “ECZTEND reported safety data consistent with placebo-controlled parental trials with a lower rate of adverse events. These results support long-term, continuous use of trelokinumab 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 and persisted during the first few weeks of treatment. After 32 weeks, 70.8% of patients reported improved sleep and 66.8% had an overall improvement in QoL. Jonathan I. Silverberg, MD, George Washington University, Washington, D.C. and American Journal of Clinical Dermatology .
First Approved The IL-13-specific therapy trelokinumab for atopic dermatitis was evaluated in multiple Phase II and Phase III trials in patients with moderate dermatitis. to severe atopic dermatitis. Participants in these trials have the option to participate in ECZTEND, a 5-year extension study designed to evaluate the long-term safety and efficacy of tralokinumab.
Combined efficacy and safety data
Blauvelt and its Colleagues report interim safety results for all patients enrolled in ECZTEND and efficacy data for patients who completed 1 year of treatment in the parental trial and extension study of tralokinumab. The study population included a heterogeneous group of patients, some of whom had received trelokinumab after the parental trial began and others who had not received an IL-13 inhibitor before adding ECZTEND.
The 2-year efficacy analysis included 345 patients with moderate or severe atopic dermatitis equally distributed by Investigator Global Assessment (IGA) at baseline in the parental trial. At ECZTEND baseline, 30.4% of patients had moderate disease activity and 5.8% had severe disease activity. The median EASI score at baseline in the parental trial was 26.7 and the median EASI score at enrollment in ECZTEND was 4.7.
Safety analysis included 1,174 patients with 1,235.7 patient-years of treatment duration. The long-term safety profile of tralokinumab was consistent with the AEs in the parental trial. The most common AEs in the maternal and extension trials were upper respiratory tract infection and atopic dermatitis. In the ECZTEND study, the incidence of AEs leading to discontinuation was low.
During the parental trial, 82.8% of 612 patients met EASI-75 response criteria, 61.0% met EASI-90 criteria, 49.7% IGA score after 1 year of tralokinumab treatment is 0/1 (clear/almost clear). For the subgroup of patients treated for an additional year in the ECZTEND study (n=345), the response rate was 82.5% for EASI-75, 59.8% for EASI-90, and 48.1% for IGA 0/1. The median EASI improvement in the 2-year subgroup was 88.0%.
Improvements in other outcomes – such as proportion of patients with EASI score ≤7, weekly pruritus score, sleep disturbance, and QoL – remained unchanged over the 2-year treatment period.
“Interim analysis of ECZTEND demonstrated favorable long-term safety and sustained efficacy of ECZTEND over up to 2 years of treatment with tralokinumab,” concluded Blauvelt and co-authors. “These data support the use of tralokinumab to specifically inhibit IL-13 as a safe and effective option for the long-term treatment of moderate to severe atopic dermatitis.”
32-Week Randomized Trial
Silverberg and colleagues report the effect of tralokinumab plus as-needed topical corticosteroids on atopic dermatitis severity and in randomized phase III Health-related quality of life over 32 weeks in the ECZTRA 3 trial. Patients were initially randomized to trelokinumab or placebo every 2 weeks. Participants who achieved an IGA 0/1 or EASI-75 response within 16 weeks were rerandomized to tralokinumab every 2 or 4 weeks and steroids as needed. Post hoc analyses included all patients initially randomized to trelokinumab, regardless of response status at 16 weeks.
The results showed that after receiving trelokinumab, the EASI-75 response rate was 70.2% at week 16, and 50.4% of patients met the EASI-90 response criteria.
Improvements in PROs, including the Eczema-Related Sleep Disturbance Rating Scale and Dermatology Life Quality Index (DLQI), persisted for 32 weeks during the first 16 weeks of IL-13 inhibitor treatment . Among patients initially receiving tralokinumab every 2 weeks, 89.9% had significant improvement in at least one of the three DLQI disease areas (disease signs/activity, pruritus, and quality of life) after 16 weeks, and 53.4% in all three There were clinically meaningful domains of improvement compared to placebo in all aspects (P
“Trokinumab plus topical corticosteroids as needed provided progressive and sustained improvement over 32 weeks in the extent and severity of atopic dermatitis and moderate to severe outcomes reported in patients with atopic dermatitis,” concluded Silverberg and co-authors. “At 32 weeks, the proportion of patients treated with tralokinumab remained low when needed with topical corticosteroids compared to placebo, demonstrating the [steroid] sparing effect of tralokinumab.”
Charles Bankhead is a Senior Editor in Oncology, which also covers Urology, Dermatology and Ophthalmology. He joined MedPage today in 2007. focus on
Both the ECZTEND and ECZTRA 3 studies were supported by LEO Pharma.
Blauvelt discloses relationships with AbbVie, Abcentra, ALIGOS, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Deravant, EcoR1, Eli Lilly, Evommune , Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi/Genzyme, Sun Pharma, UCB Pharma and Vibliome.
Silverberg discloses partnership with AbbVie , Afyx, AnaptysBio, Arcutis, Arena, Asana, Aslan, BiomX, Bluefin, Bodewell, Boehringer Ingelheim, Celgene, Connect Biopharma, Dermavant, Dermira, DS Biopharma Relationship, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Kymab, LEO Pharma, Luna, Menlo, Novartis, RAPT, Realm, Regeneron and Sanofi/Genzyme.