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

Derek K. Chu, Department of Medicine, McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada; The Research Institute of St. Joe's Hamilton, Hamilton, ON, Canada. Electronic address: chudk@mcmaster.ca.
Alexandro W. Chu, 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; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Juan José Yepes-Nuñez, Universidad de Los Andes, Bogotá, Colombia; Fundacion Santa Fe de Bogotá University, Bogotá, Colombia.
Luis Gomez-Escobar, Universidad de Los Andes, Bogotá, Colombia.
Lucia C. Pérez-Herrera, Universidad de Los Andes, Bogotá, Colombia.
Juan Pablo Díaz Martinez, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Romina Brignardello-Petersen, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Behnam Sadeghirad, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
Melanie M. Wong, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, 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.
John Basmaji, Department of Medicine, Western University, London, ON, Canada.
Margaret MacDonald, Department of Medicine, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada.
Xiajing Chu, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada; Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Nazmul Islam, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada; Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha.
Ya Gao, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada; Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Ariel Izcovich, Servicio de Clínica Médica, Hospital Aleman, Buenos Aires, Argentina.
Rachel N. Asiniwasis, Department of Dermatology, University of Saskatchewan, Regina, SK, Canada.
Mark Boguniewicz, Division of Pediatric Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Anna De Benedetto, Department of Dermatology, University of Rochester Medical Center, Rochester, NY, USA.
Korey Capozza, Global Parents for Eczema Research, Santa Barbara, CA, USA.
Lina Chen, Evidence in Allergy Group, McMaster University, Hamilton, ON, Canada; Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
Kathy Ellison, Westerville, OH, USA.
Winfred T. Frazier, Department of Family Medicine, UPMC St. Margaret, Pittsburgh, PA, USA.
Matthew Greenhawt, Division of Pediatric Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; Section of Allergy and Immunology, Children's Hospital Colorado, Aurora, CO, USA.
Joey Huynh, Sepulveda VA Medical Center, North Hills, CA, USA.
Jennifer LeBovidge, Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, 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.
Stephen A. Martin, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Monica O'Brien, Tufts University School of Medicine, Boston, MA, USA.

Document Type

Journal Article

Publication Date

9-5-2023

Journal

The Journal of allergy and clinical immunology

DOI

10.1016/j.jaci.2023.08.030

Keywords

GRADE; adverse events; atopic dermatitis; comparative effects; crisaborole; delgocitinib; difamilast; disease severity; eczema; flares (exacerbations); induction of remission; itch; lotamilast; maintenance of remission; network meta-analysis; patient-important outcomes; pimecrolimus; quality of life; reactive vs proactive therapy; roflumilast; ruxolitinib; sleep; tacrolimus; topical JAK inhibitors; topical antibiotics; topical calcineurin inhibitors; topical corticosteroids; topical phosphodiesterase-4 (PDE-4) inhibitors; topical treatments

Abstract

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. OBJECTIVES: We systematically synthesized the benefits and harms of AD prescription topical treatments. METHODS: For the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT to September 5, 2022 for randomized trials addressing AD topical treatments. 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. We classified topical corticosteroids (TCS) using seven classes-group 1 being most potent. OSF: https://osf.io/q5m6s. RESULTS: 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty, pimecrolimus improved six of seven outcomes-among the best for two; high-dose tacrolimus (0.1%) improved five-among the best for two; low-dose tacrolimus (0.03%) improved five-among the best for one. With moderate-to-high certainty, group 5 TCS improved six-among the best for three; group 4 TCS and delgocitinib improved four-among the best for two; ruxolitinib improved four-among the best for one; group 1 TCS improved three-among the best for two. These interventions did not increase harms. Crisaborole and difamilast were intermediately effective, but uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. CONCLUSIONS: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.

Department

Dermatology

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