Lebrikizumab (LEB) with topical corticosteroids (TCS) improved outcomes among patients with moderate to severe atopic dermatitis (AD) compared with TCS alone, according to results of a phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT04250337) that were published in JAMA Dermatology.
The novel ADhere trial evaluated the safety and efficacy LEB, a high-affinity monoclonal antibody targeting interleukin (IL)-13, that was conducted at 54 sites in Germany, Poland, Canada, and the United States (US) from 2020 to 2021. Adolescents and adults (N=211) with moderate to severe AD were randomly assigned in a 2:1 ratio to receive a 500 mg loading dose followed by 250 mg LEB every 2 weeks (n=145) or placebo (n=66) plus 0.1% triamcinolone acetonide cream and 1% hydrocortisone cream for 16 weeks. Patients were allowed to stop or taper TCS as needed. The primary efficacy outcomes were an Investigator’s Global Assessment (IGA) score of 0 or 1 with a 2-point or greater improvement from baseline and a 75% improvement in Eczema Area of Severity Index (EASI-75).
The intervention and control study arms comprised patients mean aged 37.5 (standard deviation [SD], 19.9) and 36.7 (SD, 17.9) years; 22.1% and 21.2% were adolescents, 48.3% and 50.0% were girls or women, 62.1% and 60.6% were White, 45.5% and 51.5% had received prior systemic treatment, and 28.3% and 33.3% prior systemic corticosteroids, respectively.
More of the LEB+TCS recipients achieved the IGA (41.2% vs 22.1%; P =.01) and EASI-75 (69.5% vs 42.2%; P <.001) primary efficacy outcomes compared with placebo recipients, respectively. A significant group difference in the EASI-75 outcome occurred as early at week 4.
In addition, LEB+TCS treatment was favored over placebo with TCS for the secondary outcomes of EASI change from baseline (mean difference [MD], -23.6%; P <.001), SCORing Atopic Dermatitis (SCORAD) change from baseline (MD, -17.7%; P <.001), EuroQol Group EQ-5D (EQ-5D-5L) United Kingdom Health Index (MD, 0.1; P <.001), EQ-5D-5L US Health Index (MD, 0.07; P <.001), Patient Oriented Eczema Measure (POEM) change from baseline (MD, -4; P <.001), and Children’s Dermatology Life Quality Index (CDLQI) change from baseline (MD, -4.6; P <.001).
Treatment-emergent adverse events occurred in 43.4% of the LEB+TCS and 34.8% of the placebo and TCS recipients. The most common events of clinical interest included infections (16.6% vs 13.6%), herpes infection (3.4% vs 1.5%), and injection site reactions (2.8% vs 1.5%) among the LEB+TCS and placebo groups, respectively. In all, 3 LEB+TCS recipients discontinued treatment due to injection site rash, drug hypersensitivity, or conjunctivitis.
The major limitation of this study was that TCS use was not accurately quantified and therefore was not accounted for in this analysis.
Study authors concluded that compared with TCS alone, LEB plus TCS for 16 weeks was associated with significantly improved AD symptoms among both adolescents and adults. These data suggested to investigators that “LEB+TCS may be an effective treatment option for adult and adolescent patients with moderate-to-severe AD.”
Disclosure: Several authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Simpson EL, Gooderham M, Wollenberg A, et al. Efficacy and safety of Lebrikizumab in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis: a randomized clinical trial (ADhere). JAMA Dermatol. Published online January 11, 2023. doi:10.1001/jamadermatol.2022.5534