Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

Atopic dermatitis (eczema) 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 network meta-analysis (comparative effectiveness, multiple treatment comparison) systemic treatments and phototherapy (light therapy, immunosuppressants, immunomodulators, DMARDs, cyclosporine, methotrexate, azathioprine, mycophenolate, cortiosteroids, narrow-band UVB), biologics (dupilumab, lebrikizumab, tralokinumab, nemolizumab)

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 29 06 2023
revised: 06 08 2023
accepted: 15 08 2023
pubmed: 8 9 2023
medline: 8 9 2023
entrez: 7 9 2023
Statut: ppublish

Résumé

Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. We sought to systematically synthesize the benefits and harms of AD systemic treatments. 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). 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. 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.

Sections du résumé

BACKGROUND BACKGROUND
Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes.
OBJECTIVE OBJECTIVE
We sought to systematically synthesize the benefits and harms of AD systemic treatments.
METHODS 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 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 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.

Identifiants

DOI: 10.1016/j.jaci.2023.08.029 PMID: 37678577
pubmed: 37678577
pii: S0091-6749(23)01112-0
doi: 10.1016/j.jaci.2023.08.029
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1470-1492

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Alexandro W L Chu (AWL)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.

Melanie M Wong (MM)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.

Daniel G Rayner (DG)

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Gordon H Guyatt (GH)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Juan Pablo Díaz Martinez (JP)

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Renata Ceccacci (R)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.

Irene X Zhao (IX)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.

Eric McMullen (E)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.

Archita Srivastava (A)

Evidence in Allergy Group, McMaster University, Hamilton, Canada; Department of Internal Medicine, Western University, London, Canada.

Jason Wang (J)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.

Aaron Wen (A)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.

Fang Chi Wang (FC)

Evidence in Allergy Group, McMaster University, Hamilton, Canada; Schulich School of Medicine & Dentistry, Western University, London, Canada.

Romina Brignardello-Petersen (R)

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Ariel Izcovich (A)

Servicio de Clínica Médica, Hospital Aleman, Buenos Aires, Argentina.

Paul Oykhman (P)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.

Kathryn E Wheeler (KE)

Department of Pediatrics, University of Florida, Gainesville, Fla.

Julie Wang (J)

Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.

Jonathan M Spergel (JM)

Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pa; Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa.

Jasvinder A Singh (JA)

Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala.

Jonathan I Silverberg (JI)

Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Peck Y Ong (PY)

Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Los Angeles, Calif; Department of Pediatrics, Keck School of Medicine of USC, Los Angeles, Calif.

Monica O'Brien (M)

Tufts University School of Medicine, Boston, Mass.

Stephen A Martin (SA)

UMass Chan Medical School, Worcester, Mass.

Peter A Lio (PA)

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.

Mary Laura Lind (ML)

School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Ariz.

Jennifer LeBovidge (J)

Division of Immunology, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.

Elaine Kim (E)

Toronto, Canada.

Joey Huynh (J)

Sepulveda VA Medical Center, North Hills, Calif.

Matthew Greenhawt (M)

Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colo; Section of Allergy and Immunology, Children's Hospital Colorado, Aurora, Colo.

Donna D Gardner (DD)

Allergy & Asthma Network, Fairfax, Va.

Winfred T Frazier (WT)

Department of Family Medicine, UPMC St. Margaret, Pittsburgh, Pa.

Kathy Ellison (K)

Westerville, Ohio.

Lina Chen (L)

Evidence in Allergy Group, McMaster University, Hamilton, Canada; Department of Pediatrics, McMaster University, Hamilton, Canada.

Korey Capozza (K)

Global Parents for Eczema Research, Santa Barbara, Calif.

Anna De Benedetto (A)

Department of Dermatology, University of Rochester Medical Center, Rochester, NY.

Mark Boguniewicz (M)

Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colo; Division of Pediatric Allergy and Clinical Immunology, National Jewish Health, Denver, Colo.

Wendy Smith Begolka (W)

National Eczema Association, Novato, Calif.

Rachel N Asiniwasis (RN)

Department of Dermatology, University of Saskatchewan, Regina, Saskatchewan, Canada.

Lynda C Schneider (LC)

Division of Immunology, Boston Children's Hospital, Boston, Mass.

Derek K Chu (DK)

Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; The Research Institute of St. Joe's Hamilton, Hamilton, Canada. Electronic address: chudk@mcmaster.ca.

Classifications MeSH