A combination regimen consisting of upadacitinib and topical corticosteroids was superior to topical corticosteroids and placebo for reducing the extent and severity of eczema in adolescents and adult patients with moderate to severe atopic dermatitis (AD), according to study findings published in the Lancet.
The multicenter, phase 3 trial included adults from 18 to 75 years of age as well as adolescents from 12 to 17 years of age who had moderate to severe AD that affected 10% or more of body surface area. Patients presented with Eczema Area and Severity Index [EASI] score of 16 or greater, a validated Investigator’s Global Assessment for AD (vIGA-AD) score of 3 or greater, as well as a weekly average Worst Pruritus Numerical Rating Scale score of 4 or greater.
Participants were randomly assigned to either once daily 15 mg upadacitinib plus topical corticosteroids (n=300), once daily 30 mg upadacitinib plus topical corticosteroids (n=297), or placebo plus topical corticosteroids (n=304). Treatment lasted for 16 weeks.
At the end of 16 weeks, the coprimary endpoint of the percentage of patients achieving a 75% or greater reduction in EASI score (EASI-75) from baseline was significantly higher in the 15 mg upadacitinib group (65%) and the 30 mg upadacitinib arm (77%) compared with the placebo group (26%; adjusted difference, 38.1%; 95% CI, 30.8–45.4 for the upadacitinib 15 mg group and 50.6%; 95% CI, 43.8–57.4 for the upadacitinib 30 mg group; P <.0001 for both).
Another coprimary endpoint was the percentage of patients who achieved a vIGA-AD response, which was defined as a vIGA-AD score of 0 (clear) or 1 (almost clear) with 2 or more grades of improvement.
Similar to the EASI-75 endpoint, the 16-week vIGA-AD response was significantly higher in the group of patients who received 15 mg upadacitinib plus topical corticosteroids (40%) and 30 mg upadacitinib plus topical corticosteroids (59%) compared with those in the placebo arm (11%; adjusted difference vs placebo, 28.5%; 95% CI, 22.1–34.9 for 15 mg upadacitinib and 47.6%; 95% CI, 41.1–54.0 for 30 mg upadacitinib; P <.0001 for both).
Overall, both doses of upadacitinib were well tolerated with topical corticosteroids during the double-blind study period. Acne, nasopharyngitis, oral herpes, upper respiratory tract infection, increased levels of blood creatine phosphokinase, headache, and AD were the most frequently reported treatment-emergent adverse events (AEs).
The incidence rate of AEs which led study drug discontinuation was 1% in the 30 mg upadacitinib group and 2% in the placebo arm. The rates of serious AEs were similar across treatment groups.
Limitations of this study included its relatively short follow-up duration as well as the underrepresentation of Black (4%-6%) and Asian (20%-21%) patients.
The investigators concluded that since a significant percentage of patients in this study discontinued topical corticosteroids “while maintaining a strong treatment response at week 16,” this suggests “upadacitinib therapy could align with steroid-sparing treatment goals” for this population.
Disclosure: This clinical trial was supported by AbbVie. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Reich K, Teixeira HD, de Bruin-Weller M, et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021;397(10290):2169-2181. doi:10.1016/S0140-6736(21)00589-4