Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids: Systematic Review and Network Meta-analysis

Jonathan I Silverberg; H Chih-Ho Hong; Jacob P Thyssen; Brian M Calimlim; Avani Joshi; Henrique D Teixeira; Eric B Collins; Marjorie M Crowell; Scott J Johnson; April W Armstrong

doi:10.1007/s13555-022-00721-1

Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids: Systematic Review and Network Meta-analysis

Dermatol Ther (Heidelb). 2022 May;12(5):1181-1196. doi: 10.1007/s13555-022-00721-1. Epub 2022 Apr 18.

Authors

Affiliations

¹ Department of Dermatology, The George Washington University School of Medicine and Health Sciences, 2150 Pennsylvania Ave NW, Ste 2B-425, Washington, DC, 20037, USA. jonathanisilverberg@gmail.com.
² Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
³ Probity Medical Research, Surrey, BC, Canada.
⁴ Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
⁵ AbbVie Inc, North Chicago, IL, USA.
⁶ Medicus Economics LLC, Boston, MA, USA.
⁷ Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Abstract

Introduction: The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD.

Methods: The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis.

Results: Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily.

Discussion: Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment.

Conclusion: Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD.

Keywords: Atopic dermatitis; EASI; IGA; Network meta-analysis; Pruritus NRS; Systematic literature review.