TY - JOUR
T1 - Systemic treatments for atopic dermatitis (eczema)
T2 - Systematic review and network meta-analysis of randomized trials
AU - Chu, Alexandro W.L.
AU - Wong, Melanie M.
AU - Rayner, Daniel G.
AU - Guyatt, Gordon H.
AU - Díaz Martinez, Juan Pablo
AU - Ceccacci, Renata
AU - Zhao, Irene X.
AU - McMullen, Eric
AU - Srivastava, Archita
AU - Wang, Jason
AU - Wen, Aaron
AU - Wang, Fang Chi
AU - Brignardello-Petersen, Romina
AU - Izcovich, Ariel
AU - Oykhman, Paul
AU - Wheeler, Kathryn E.
AU - Wang, Julie
AU - Spergel, Jonathan M.
AU - Singh, Jasvinder A.
AU - Silverberg, Jonathan I.
AU - Ong, Peck Y.
AU - O'Brien, Monica
AU - Martin, Stephen A.
AU - Lio, Peter A.
AU - Lind, Mary Laura
AU - LeBovidge, Jennifer
AU - Kim, Elaine
AU - Huynh, Joey
AU - Greenhawt, Matthew
AU - Gardner, Donna D.
AU - Frazier, Winfred T.
AU - Ellison, Kathy
AU - Chen, Lina
AU - Capozza, Korey
AU - De Benedetto, Anna
AU - Boguniewicz, Mark
AU - Smith Begolka, Wendy
AU - Asiniwasis, Rachel N.
AU - Schneider, Lynda C.
AU - Chu, Derek K.
N1 - Publisher Copyright:
© 2023
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Atopic dermatitis (eczema)
KW - Janus kinase (JAK) inhibitors (upadacitinib, abrocitinib, baricitinib), patient-important outcomes and adverse events or adverse reactions, disease severity, itch, sleep, itch and sleep disturbance quality of life
KW - network meta-analysis (comparative effectiveness, multiple treatment comparison)
KW - systemic treatments and phototherapy (light therapy, immunosuppressants, immunomodulators, DMARDs, cyclosporine, methotrexate, azathioprine, mycophenolate, cortiosteroids, narrow-band UVB), biologics (dupilumab, lebrikizumab, tralokinumab, nemolizumab)
UR - http://www.scopus.com/inward/record.url?scp=85177733172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85177733172&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2023.08.029
DO - 10.1016/j.jaci.2023.08.029
M3 - Article
C2 - 37678577
AN - SCOPUS:85177733172
SN - 0091-6749
VL - 152
SP - 1470
EP - 1492
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -