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Lebrikizumab treatment leads to encouraging outcomes in multiple traits of AD

Presented by
Prof. Jonathan Silverberg, George Washington University School of Medicine, USA
AAD 2022
Phase 3, ADvocate 1; ADvocate 2
Significant reductions in eczema, sleep loss, and itch were observed in patients treated with the IL-13 blocker lebrikizumab for atopic dermatitis (AD). These results of the phase 3 ADvocate1 and ADvocate2 trials were also reflected in a meaningful improvement of quality of life.

IL-13 plays a key role in the multifactorial pathogenesis of AD [1,2]. It not only promotes inflammation but also negatively influences the function of the epidermal barrier. Lebrikizumab selectively targets soluble IL-13 resulting in the inhibition of IL-13 signalling [3]. The 2 randomised, double-blind, placebo-controlled, phase 3 trials ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) assessed lebrikizumab as monotherapy for moderate-to-severe AD. Prof. Jonathan Silverberg (George Washington University School of Medicine, Washington DC, USA) presented the 16-week interim results of the ongoing, 52-week studies.

The studies comprised 851 adult and adolescent AD patients. The mean age in the different groups ranged from 34.2 to 36.6 years, the mean BMI from 26.2 to 27.8, and over half of the participants had a history of prior systemic treatment. Between 34.9% and 41.1% suffered from severe AD. The primary efficacy endpoints were defined as an Investigator Global Assessment (IGA) of 0/1 with a minimum of 2-point amelioration from baseline, and achievement of Eczema Area and Severity Index (EASI)75. Major secondary endpoints were EASI90, change in pruritus, sleep loss, and Dermatology Life Quality Index (DLQI).

Active treatment with 250 mg lebrikizumab every 2 weeks was significantly superior to placebo in both studies. At week 16, 43% of participants reached IGA 0/1 versus 12.8% on placebo (P<0.001) in ADvocate1 and 33.1% versus 10.9% (P<0.001) in ADvocate2. The corresponding proportions for EASI75 were 59.3% versus 16.4% (P<0.001) and 50.8% versus 18.2% (P<0.001), respectively. Of note, the differences between lebrikizumab and placebo were significant as of week 4 for both measures. EASI90 rates in the 2 trials were 38.2% and 30.2% (P<0.001 vs placebo), respectively.

Furthermore, a ≥4-point improvement of pruritus on the numeric rating scale occurred in 46.3% and 38.3% of those taking lebrikizumab compared with 12.7% and 11.3% randomised to placebo. High rates of DLQI ≥4-point enhancement (75.5% and 64.4%; P<0.001) were observed, as well as sleep-loss improvement (38.7% and 26.5%; P<0.001). “These are clinically relevant results,” emphasised Prof. Silverberg.

Percentages with any kind of treatment-emergent adverse events were overall higher in the placebo than in the lebrikizumab groups (51.5% vs 45.4% in ADvocate1 and 66.2% vs 53% in ADvocate2). A signal for conjunctivitis was observed with 7.4% and 7.8% in the active groups compared with 2.8% and 2.1% on placebo, but all cases were mild to moderate.

“We are really looking forward to the 52-week data,” Prof. Silverberg concluded in light of these positive results at week 16.

    1. Gonçalves F, et al. Drugs Context. 2021;10:2021-1-7.
    2. Simpson EL, et al. J Am Acad Dermatol. 2018;78(5):863–871.
    3. Silverberg JI, et al. Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: results from two Phase 3, randomized, double-blinded, placebo-controlled trials. S026, AAD 2022 Annual Meeting, 25–29 March, Boston, MA, USA.

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