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Published in: Dermatology and Therapy 10/2023

Open Access 01-09-2023 | Atopic Dermatitis | Original Research

Comparative Efficacy of Targeted Systemic Therapies for Moderate-to-Severe Atopic Dermatitis without Topical Corticosteroids: An Updated Network Meta-analysis

Authors: Jonathan I. Silverberg, H. Chih-ho Hong, Brian M. Calimlim, Wan-Ju Lee, Henrique D. Teixeira, Eric B. Collins, Marjorie M. Crowell, Scott J. Johnson, April W. Armstrong

Published in: Dermatology and Therapy | Issue 10/2023

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Abstract

Introduction

The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate-to-severe AD.

Methods

Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181–1196, 2022). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis.

Results

The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes.

Conclusions

Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient’s personalized treatment plan.
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Literature
1.
go back to reference Silverberg JI, Hong HC, Thyssen JP, et al. Comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis without topical corticosteroids: systematic review and network meta-analysis. Dermatol Ther (Heidelb). 2022;12(5):1181–96.CrossRefPubMed Silverberg JI, Hong HC, Thyssen JP, et al. Comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis without topical corticosteroids: systematic review and network meta-analysis. Dermatol Ther (Heidelb). 2022;12(5):1181–96.CrossRefPubMed
2.
go back to reference Silverberg JI, Guttman-Yassky E, Thaçi D, et al. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N Engl J Med. 2023;388(12):1080–91.CrossRefPubMed Silverberg JI, Guttman-Yassky E, Thaçi D, et al. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N Engl J Med. 2023;388(12):1080–91.CrossRefPubMed
5.
go back to reference Simpson E, Bissonnette R, Eichenfield LF, et al. The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): the development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis. J Am Acad Dermatol. 2020;83(3):839–46.CrossRefPubMed Simpson E, Bissonnette R, Eichenfield LF, et al. The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): the development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis. J Am Acad Dermatol. 2020;83(3):839–46.CrossRefPubMed
6.
go back to reference Leshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol. 2015;172(5):1353–7.CrossRefPubMed Leshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol. 2015;172(5):1353–7.CrossRefPubMed
7.
go back to reference Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol. 2019;181(4):761–9.CrossRefPubMedPubMedCentral Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol. 2019;181(4):761–9.CrossRefPubMedPubMedCentral
9.
go back to reference Cope S, Zhang J, Saletan S, Smiechowski B, Jansen JP, Schmid P. A process for assessing the feasibility of a network meta-analysis: a case study of everolimus in combination with hormonal therapy versus chemotherapy for advanced breast cancer. BMC Med. 2014;12:93.CrossRefPubMedPubMedCentral Cope S, Zhang J, Saletan S, Smiechowski B, Jansen JP, Schmid P. A process for assessing the feasibility of a network meta-analysis: a case study of everolimus in combination with hormonal therapy versus chemotherapy for advanced breast cancer. BMC Med. 2014;12:93.CrossRefPubMedPubMedCentral
10.
go back to reference Bosma AL, Spuls PI, Garcia-Doval I, et al. TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema. Br J Dermatol. 2020;182(6):1423–9.CrossRefPubMed Bosma AL, Spuls PI, Garcia-Doval I, et al. TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema. Br J Dermatol. 2020;182(6):1423–9.CrossRefPubMed
11.
go back to reference Bosma AL, de Wijs LEM, Hof MH, et al. Long-term effectiveness and safety of treatment with dupilumab in patients with atopic dermatitis: results of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry. J Am Acad Dermatol. 2020;83(5):1375–84.CrossRefPubMed Bosma AL, de Wijs LEM, Hof MH, et al. Long-term effectiveness and safety of treatment with dupilumab in patients with atopic dermatitis: results of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry. J Am Acad Dermatol. 2020;83(5):1375–84.CrossRefPubMed
12.
go back to reference Chou JS, LeBovidge J, Timmons K, Elverson W, Morrill J, Schneider LC. Predictors of clinical success in a multidisciplinary model of atopic dermatitis treatment. Allergy Asthma Proc. 2011;32(5):377–83.CrossRefPubMed Chou JS, LeBovidge J, Timmons K, Elverson W, Morrill J, Schneider LC. Predictors of clinical success in a multidisciplinary model of atopic dermatitis treatment. Allergy Asthma Proc. 2011;32(5):377–83.CrossRefPubMed
13.
go back to reference Plummer M. JAGS: a program for analysis of Bayesian graphical models using Gibbs sampling. 4.3.0 ed. Plummer M. JAGS: a program for analysis of Bayesian graphical models using Gibbs sampling. 4.3.0 ed.
14.
go back to reference Team RC. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2020. Team RC. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2020.
15.
go back to reference Seo M, Schmid C. bnma: Bayesian Network Meta-Analysis using 'JAGS'. R package version 1.4.0. Seo M, Schmid C. bnma: Bayesian Network Meta-Analysis using 'JAGS'. R package version 1.4.0.
16.
go back to reference Dias S, Welton NJ, Sutton AJ, Ades AE. NICE Decision Support Unit Technical Support Documents. NICE DSU Technical support document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. London: National Institute for Health and Care Excellence (NICE) Copyright © 2014 National Institute for Health and Clinical Excellence, unless otherwise stated. All rights reserved.; 2014. Dias S, Welton NJ, Sutton AJ, Ades AE. NICE Decision Support Unit Technical Support Documents. NICE DSU Technical support document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. London: National Institute for Health and Care Excellence (NICE) Copyright © 2014 National Institute for Health and Clinical Excellence, unless otherwise stated. All rights reserved.; 2014.
17.
go back to reference Dias S, Ades AE, Welton NJ, Jansen JP, Sutton AJ. Network meta-analysis for decision-making. Wiley; 2018.CrossRef Dias S, Ades AE, Welton NJ, Jansen JP, Sutton AJ. Network meta-analysis for decision-making. Wiley; 2018.CrossRef
18.
go back to reference Thaçi D, Simpson EL, Deleuran M, et al. Efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2). J Dermatol Sci. 2019;94(2):266–75.CrossRefPubMed Thaçi D, Simpson EL, Deleuran M, et al. Efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2). J Dermatol Sci. 2019;94(2):266–75.CrossRefPubMed
19.
go back to reference Drucker AM, Morra DE, Prieto-Merino D, et al. Systemic immunomodulatory treatments for atopic dermatitis: update of a living systematic review and network meta-analysis. JAMA Dermatol. 2022;158(5):523–32.CrossRefPubMedPubMedCentral Drucker AM, Morra DE, Prieto-Merino D, et al. Systemic immunomodulatory treatments for atopic dermatitis: update of a living systematic review and network meta-analysis. JAMA Dermatol. 2022;158(5):523–32.CrossRefPubMedPubMedCentral
20.
go back to reference Pereyra-Rodriguez JJ, Alcantara-Luna S, Domínguez-Cruz J, et al. Short-term effectiveness and safety of biologics and small molecule drugs for moderate to severe atopic dermatitis: a systematic review and network meta-analysis. Life (Basel). 2021;11(9):927.PubMedPubMedCentral Pereyra-Rodriguez JJ, Alcantara-Luna S, Domínguez-Cruz J, et al. Short-term effectiveness and safety of biologics and small molecule drugs for moderate to severe atopic dermatitis: a systematic review and network meta-analysis. Life (Basel). 2021;11(9):927.PubMedPubMedCentral
21.
go back to reference Wan H, Jia H, Xia T, Zhang D. Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: a network meta-analysis. Dermatol Ther. 2022;35(9): e15636.CrossRefPubMedPubMedCentral Wan H, Jia H, Xia T, Zhang D. Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: a network meta-analysis. Dermatol Ther. 2022;35(9): e15636.CrossRefPubMedPubMedCentral
22.
go back to reference Silverberg JI, Thyssen JP, Fahrbach K, et al. Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis. J Eur Acad Dermatol Venereol. 2021;35(9):1797–810.CrossRefPubMedPubMedCentral Silverberg JI, Thyssen JP, Fahrbach K, et al. Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis. J Eur Acad Dermatol Venereol. 2021;35(9):1797–810.CrossRefPubMedPubMedCentral
23.
go back to reference Zhang L, Wang L, Jiang X. The efficacy of Janus kinase inhibitors in patients with atopic dermatitis: a systematic review and network meta-analysis. Dermatol Ther. 2021;34(5): e15098.CrossRefPubMed Zhang L, Wang L, Jiang X. The efficacy of Janus kinase inhibitors in patients with atopic dermatitis: a systematic review and network meta-analysis. Dermatol Ther. 2021;34(5): e15098.CrossRefPubMed
24.
go back to reference Mostafa N, Phan K, Lai B, Smith SD. Comparing quality of life outcomes of JAK inhibitors and biological treatments for atopic dermatitis: a systematic review and network meta-analysis. Expert Rev Clin Pharmacol. 2021;14(11):1435–44.CrossRefPubMed Mostafa N, Phan K, Lai B, Smith SD. Comparing quality of life outcomes of JAK inhibitors and biological treatments for atopic dermatitis: a systematic review and network meta-analysis. Expert Rev Clin Pharmacol. 2021;14(11):1435–44.CrossRefPubMed
25.
go back to reference De Bruin-Weller M, Biedermann T, Bissonnette R, et al. Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies. Acta Derm Venereol. 2021;101(2):adv00402.CrossRefPubMed De Bruin-Weller M, Biedermann T, Bissonnette R, et al. Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies. Acta Derm Venereol. 2021;101(2):adv00402.CrossRefPubMed
26.
go back to reference Silverberg JI, Gooderham M, Katoh N, et al. 327 Optimizing the management of atopic dermatitis with a new minimal disease activity concept and criteria and consensus-based recommendations for systemic therapy. Br J Dermatol. 2023;188(Supplement_2):ljac140.022.CrossRef Silverberg JI, Gooderham M, Katoh N, et al. 327 Optimizing the management of atopic dermatitis with a new minimal disease activity concept and criteria and consensus-based recommendations for systemic therapy. Br J Dermatol. 2023;188(Supplement_2):ljac140.022.CrossRef
27.
28.
go back to reference Silverberg JI, Gooderham M, Thyssen JP, et al. 419 Patient satisfaction with treatments for moderate-to-severe atopic dermatitis according to degree and speed of skin and itch improvements: results from a patient survey in the United States. Br J Dermatol. 2023;188(Supplement_3):ljad162.039. https://doi.org/10.1093/bjd/ljad162.039. Silverberg JI, Gooderham M, Thyssen JP, et al. 419 Patient satisfaction with treatments for moderate-to-severe atopic dermatitis according to degree and speed of skin and itch improvements: results from a patient survey in the United States. Br J Dermatol. 2023;188(Supplement_3):ljad162.039. https://​doi.​org/​10.​1093/​bjd/​ljad162.​039.
Metadata
Title
Comparative Efficacy of Targeted Systemic Therapies for Moderate-to-Severe Atopic Dermatitis without Topical Corticosteroids: An Updated Network Meta-analysis
Authors
Jonathan I. Silverberg
H. Chih-ho Hong
Brian M. Calimlim
Wan-Ju Lee
Henrique D. Teixeira
Eric B. Collins
Marjorie M. Crowell
Scott J. Johnson
April W. Armstrong
Publication date
01-09-2023
Publisher
Springer Healthcare
Published in
Dermatology and Therapy / Issue 10/2023
Print ISSN: 2193-8210
Electronic ISSN: 2190-9172
DOI
https://doi.org/10.1007/s13555-023-01000-3

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