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

Alexandro W. Chu, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada. Electronic address: chudk@mcmaster.ca.
Melanie M. Wong, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada.
Daniel G. Rayner, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Gordon H. Guyatt, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Juan Pablo Martinez, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Renata Ceccacci, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada.
Irene X. Zhao, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada.
Eric McMullen, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada.
Archita Srivastava, Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada; Department of Internal Medicine, Western University, London, ON, Canada.
Jason Wang, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada.
Aaron Wen, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada.
Fang Chi Wang, Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada; Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
Romina Brignardello-Petersen, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Ariel Izcovich, Servicio de Clínica Médica, Hospital Aleman, Buenos Aires, Argentina.
Paul Oykhman, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada.
Kathryn E. Wheeler, Department of Pediatrics, University of Florida, Gainesville, USA.
Julie Wang, Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Jonathan M. Spergel, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Jasvinder A. Singh, Department of Medicine, University of Alabama at Birmingham, AL, USA.
Jonathan I. Silverberg, Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Peck Y. Ong, Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Pediatrics, USC Keck School of Medicine, Los Angeles, CA, USA.
Monica O'Brien, Tufts University School of Medicine, Boston, MA, USA.
Stephen A. Martin, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Peter A. Lio, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mary Laura Lind, School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, USA.
Jennifer LeBovidge, Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Elaine Kim, Toronto, ON, Canada.
Joey Huynh, Sepulveda VA Medical Center, North Hills, CA, USA.
Matthew Greenhawt, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA; Section of Allergy and Immunology, Children's Hospital Colorado, Aurora, CO, USA.
Donna D. Gardner, Allergy & Asthma Network, Fairfax, VA, USA.
Winfred T. Frazier, Department of Family Medicine, UPMC St. Margaret, Pittsburgh, PA, USA.
Kathy Ellison, Westerville, OH, USA.

Document Type

Journal Article

Publication Date

9-5-2023

Journal

The Journal of allergy and clinical immunology

DOI

10.1016/j.jaci.2023.08.029

Keywords

GRADE; JAK inhibitors; Janus Kinase; abrocitinib; adverse events; atopic dermatitis; azathioprine; baricitinib; biologics; comparative effects; corticosteroids; cyclosporine; disease severity; dupilumab; eczema; immunomodulators; immunosuppressants; itch; lebrikizumab; light therapy; methotrexate; monoclonal antibodies; mycophenolate; narrow-band UVB; nemolizumab; network meta-analysis; patient-important outcomes; phototherapy; quality of life; sleep; systemic treatments; tralokinumab; upadacitinib

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 systematic synthesized the benefits and harms of AD systemic treatments. METHODS: For the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT, 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-quality of life, flares, and harms. The GRADE approach informed certainty of evidence ratings. OSF: https://osf.io/e5sna. RESULTS: 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty, high-dose upadacitinib was among the most effective for five of six patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for two outcomes. These JAK inhibitors were among the most harmful in increasing adverse events. With high-certainty, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest-modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. The 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 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 favorable safety.

Department

Dermatology

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