Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials - 07/12/23

Doi : 10.1016/j.jaci.2023.08.029

Alexandro W.L. Chu, BHSc ^a,^b, Melanie M. Wong, MD ^a,^b, Daniel G. Rayner, BHSc ^c, Gordon H. Guyatt, MD, MSc, OC ^a,^b,^c, Juan Pablo Díaz Martinez, MSc ^c, Renata Ceccacci, MD ^a,^b, Irene X. Zhao, BHSc ^a,^b, Eric McMullen, BSc ^a,^b, Archita Srivastava, MD ^b,^d, Jason Wang, BSc ^a,^b, Aaron Wen, BHSc ^a,^b, Fang Chi Wang, BHSc ^b,^e, Romina Brignardello-Petersen, DDS, MSc, PhD ^c, Ariel Izcovich, MD, PhD ^f, Paul Oykhman, MD, MSc ^a,^b, Kathryn E. Wheeler, MD ^g, Julie Wang, MD ^h, Jonathan M. Spergel, MD, PhD ^i,^j, Jasvinder A. Singh, MD, MPH ^k, Jonathan I. Silverberg, MD, MPH, PhD ^l, Peck Y. Ong, MD ^m,ⁿ, Monica O’Brien, MBS ^o, Stephen A. Martin, MD, EdM ^p, Peter A. Lio, MD ^q,^r, Mary Laura Lind, PhD ^s, Jennifer LeBovidge, PhD ^t,^u, Elaine Kim, BScPhm, RPh ^v, Joey Huynh, MPT ^w, Matthew Greenhawt, MD, MBA, MSc ^x,^y, Donna D. Gardner, DrPH ^z, Winfred T. Frazier, MD, MPH ^aa, Kathy Ellison, MEd ^bb, Lina Chen, MD ^b,^cc, Korey Capozza, MPH ^dd, Anna De Benedetto, MD ^ee, Mark Boguniewicz, MD ^x,^ff, Wendy Smith Begolka, MBS ^gg, Rachel N. Asiniwasis, MD, MS ^hh, Lynda C. Schneider, MD ^t, Derek K. Chu, MD, PhD ^a,^b,^c,^ii,^⁎
^a Department of Medicine, McMaster University, Hamilton, Canada
^b Evidence in Allergy Group, McMaster University, Hamilton, Canada
^c Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
^d Department of Internal Medicine, Western University, London, Canada
^e Schulich School of Medicine & Dentistry, Western University, London, Canada
^f Servicio de Clínica Médica, Hospital Aleman, Buenos Aires, Argentina
^g Department of Pediatrics, University of Florida, Gainesville, Fla
^h Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY
ⁱ Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pa
^j Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, Pa
^k Department of Medicine, University of Alabama at Birmingham, Birmingham, Ala
^l Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC
^m Division of Clinical Immunology and Allergy, Children’s Hospital Los Angeles, Los Angeles, Calif
ⁿ Department of Pediatrics, Keck School of Medicine of USC, Los Angeles, Calif
^o Tufts University School of Medicine, Boston, Mass
^p UMass Chan Medical School, Worcester, Mass
^q Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Ill
^r Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill
^s School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Ariz
^t Division of Immunology, Boston Children’s Hospital, Boston, Mass
^u Harvard Medical School, Boston, Mass
^v Toronto, Canada
^w Sepulveda VA Medical Center, North Hills, Calif
^x Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colo
^y Section of Allergy and Immunology, Children’s Hospital Colorado, Aurora, Colo
^z Allergy & Asthma Network, Fairfax, Va
^aa Department of Family Medicine, UPMC St. Margaret, Pittsburgh, Pa
^bb Westerville, Ohio
^cc Department of Pediatrics, McMaster University, Hamilton, Canada
^dd Global Parents for Eczema Research, Santa Barbara, Calif
^ee Department of Dermatology, University of Rochester Medical Center, Rochester, NY
^ff Division of Pediatric Allergy and Clinical Immunology, National Jewish Health, Denver, Colo
^gg National Eczema Association, Novato, Calif
^hh Department of Dermatology, University of Saskatchewan, Regina, Saskatchewan, Canada
ⁱⁱ The Research Institute of St. Joe’s Hamilton, Hamilton, Canada

^∗Corresponding author: Derek K. Chu, MD, PhD, Department of Medicine and Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON L8S 4K1, Canada.Department of Medicine and Department of Health Research MethodsEvidenceand ImpactMcMaster UniversityHamiltonONL8S 4K1Canada

Graphical abstract

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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 (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.

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Key words : Atopic dermatitis (eczema), systemic treatments and phototherapy (light therapy, immunosuppressants, immunomodulators, DMARDs, cyclosporine, methotrexate, azathioprine, mycophenolate, cortiosteroids, narrow-band UVB), biologics (dupilumab, lebrikizumab, tralokinumab, nemolizumab), 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)

Abbreviations used : AAAAI, ACAAI, AD, CrI, DLQI, EASI, GRADE, HOME, IQR, JAK, MD, MID, NMA, NRS, OR, ORAL, POEM, QoL, RCT

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Vol 152 - N° 6

P. 1470-1492 - décembre 2023 Retour au numéro

Article précédent

Dupilumab strengthens herpes simplex virus type 1–specific immune responses in atopic dermatitis
Stephan Traidl, Leonard Harries, Petra Kienlin, Gabriele Begemann, Lennart M. Roesner, Thomas Werfel

| Article suivant

Topical treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials
Derek K. Chu, Alexandro W.L. Chu, Daniel G. Rayner, Gordon H. Guyatt, Juan José Yepes-Nuñez, Luis Gomez-Escobar, Lucia C. Pérez-Herrera, Juan Pablo Díaz Martinez, Romina Brignardello-Petersen, Behnam Sadeghirad, Melanie M. Wong, Renata Ceccacci, Irene X. Zhao, John Basmaji, Margaret MacDonald, Xiajing Chu, Nazmul Islam, Ya Gao, Ariel Izcovich, Rachel N. Asiniwasis, Mark Boguniewicz, Anna De Benedetto, Korey Capozza, Lina Chen, Kathy Ellison, Winfred T. Frazier, Matthew Greenhawt, Joey Huynh, Jennifer LeBovidge, Peter A. Lio, Stephen A. Martin, Monica O’Brien, Peck Y. Ong, Jonathan I. Silverberg, Jonathan M. Spergel, Wendy Smith Begolka, Julie Wang, Kathryn E. Wheeler, Donna D. Gardner, Lynda Schneider

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Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials - 07/12/23

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Abstract

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Methods

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