Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials
A. Chu, Melanie Wong, Daniel Rayner, Gordon Guyatt, Juan Pablo Díaz Martinez, Renata Ceccacci, Irene X. Zhao, Eric McMullen, Archita Srivastava, Jason Wang, Aaron Wen, Fang Wang, Romina Brignardello‐Petersen, Ariel Izcovich, Paul Oykhman, Kathryn E. Wheeler, Julie Wang, Jonathan M. Spergel, Jasvinder A. Singh, Jonathan I. Silverberg, Peck Y. Ong, Monica O’Brien, Stephen A. Martin, Peter Lio, Mary Laura Lind, Jennifer LeBovidge, Elaine Kim, Joey Huynh, Matthew Greenhawt, Donna D. Gardner, Winfred Frazier, Kathy Ellison, Lina Chen, Korey Capozza, Anna De Benedetto, Mark Boguniewicz, Wendy Smith Begolka, Rachel N. Asiniwasis, Lynda C. Schneider, Derek K. Chu
Abstract
BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.