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. 2022 May 1;158(5):523-532.
doi: 10.1001/jamadermatol.2022.0455.

Systemic Immunomodulatory Treatments for Atopic Dermatitis: Update of a Living Systematic Review and Network Meta-analysis

Aaron M Drucker  1   2 , Deanna E Morra  3 , David Prieto-Merino  4 , Alexandra G Ellis  5 , Zenas Z N Yiu  6 , Bram Rochwerg  7 , Sonya Di Giorgio  8 , Bernd W M Arents  9 , Tim Burton  10 , Phyllis I Spuls  11 , Jochen Schmitt  12 , Carsten Flohr  4
Affiliations

Systemic Immunomodulatory Treatments for Atopic Dermatitis: Update of a Living Systematic Review and Network Meta-analysis

Aaron M Drucker et al. JAMA Dermatol. .

Abstract

Importance: Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety estimates for treatments that have not been compared head to head.

Objective: To compare reported measures of efficacy and assessments of safety in clinical trials of systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis.

Data sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of EczemA Trials database, and trial registries were searched through June 15, 2021.

Study selection: Randomized clinical trials examining 8 or more weeks of treatment with systemic immunomodulatory medications for moderate-to-severe atopic dermatitis were included after screening titles, abstracts, and papers in duplicate.

Data extraction and synthesis: Data were abstracted in duplicate. Bayesian network meta-analyses and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed. The updated analysis was completed from June to December 2021.

Main outcomes and measures: Outcomes include change in Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS).

Results: Since October 2019, 21 new studies were added, for a total of 60 trials with 16 579 patients. Up to 16 weeks of treatment in adults, abrocitinib, 200 mg daily (mean difference [MD], 2.2; 95% credible interval [CrI], 0.2-4.0; high certainty) and upadacitinib, 30 mg daily (MD, 2.7; 95% CrI, 0.6-4.7; high certainty) were associated with reduced EASI slightly more than dupilumab, 600 mg then 300 mg every 2 weeks. Abrocitinib, 100 mg daily (MD, -2.1; 95% CrI, -4.1 to -0.3; high certainty), baricitinib, 4 mg daily (MD, -3.2; 95% CrI, -5.7 to -0.8; high certainty), baricitinib, 2 mg daily (MD, -5.2; 95% CrI, -7.5 to -2.9; high certainty) and tralokinumab, 600 mg then 300 mg every 2 weeks (MD, -3.5; 95% CrI, -5.8 to -1.3; high certainty) were associated with reduced EASI slightly less than dupilumab. There was little or no difference between upadacitinib, 15 mg daily, and dupilumab (MD, 0.2; 95% CrI, -1.9 to 2.2; high certainty). The pattern of results was similar for POEM, DLQI, and PP-NRS.

Conclusions and relevance: In this systematic review and meta-analysis, abrocitinib, 200 mg; and upadacitinib, 30 mg daily, were associated with slightly better scores than dupilumab, and upadacitinib, 15 mg daily, was associated with similar scores to dupilumab. Abrocitinib, 100 mg daily, baricitinib, 4 mg and 2 mg daily, and tralokinumab, 300 mg, every 2 weeks were associated with slightly worse scores.

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Conflict of interest statement

Conflict of Interest Disclosures: The authors declare no potential conflicts of interest involving the work under consideration for publication. Dr Drucker has received compensation from the British Journal of Dermatology (reviewer and Section Editor), American Academy of Dermatology (guidelines writer), and National Eczema Association (grant reviewer). He has been a paid consultant for the Canadian Agency for Drugs and Technology in Health. Dr Ellis is an employee of Stratevi, LLC, a healthcare consultancy that receives financial compensation from numerous pharmaceutical companies; Stratevi had no involvement with the submitted work. Dr Spuls has done consultancies in the past for Sanofi (111017) and AbbVie (041217) (unpaid), was principal investigator of the MAcAD RCTs (Schram et al, JACI 2011, Roekevisch et al, JACI 2018, Gerbens et al, BJD 2018), receives departmental independent research grants for TREAT NL registry, for which she is chief investigator, from pharma companies since December 2019, is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of skin conditions such as psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital. Dr Schmitt received institutional funding for investigator-initiated trials from Novartis, Sanofi, Pfizer, ALK. He received fees for consulting from Novartis and Pfizer. He is co-principal investigatorof the German National Atopic Dermatitis Registry TREAT germany, which is funded by Sanofi Aventis Deutschland GmbH, Galderma SA, LEO Pharma GmbH, and Lilly Deutschland GmbH. Dr Flohr is Chief Investigator of the UK National Institute for Health Research-funded TREAT (ISRCTN15837754) and SOFTER (Clinicaltrials.gov: NCT03270566) trials as well as the UK-Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918), and a principal investigator in the European Union (EU) Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu/). He also leads the EU Trans-Foods consortium. His department has received funding from Sanofi-Genzyme for skin microbiome work. No other conflicts were reported.

Figures

Figure 1.
Figure 1.. Study Selection Flow Diagram
aTwo studies included in a single reference. bOne study identified through other sources.
Figure 2.
Figure 2.. Network Graphs of Studies Included in the Analysis of Adults Treated Between 8 and 16 Weeks
Change in (A) Eczema Area and Severity Index (EASI), (B) Patient Oriented Eczema Measure (POEM). The width of each line connecting 2 treatments (nodes) is proportional to the number of head-to-head trials for that comparison. BID indicates twice per day; OD, once daily; q1w, once weekly; q2w, every 2 weeks; q4w, every 4 weeks.
Figure 3.
Figure 3.. Network Graphs of Studies Included in the Analysis of Adults Treated Between 8 and 16 Weeks
A, Dermatology Life Quality Index (DLQI), and (B) Peak Pruritus Numeric Rating Scales (PP-NRS). The width of each line connecting 2 treatments (nodes) is proportional to the number of head-to-head trials for that comparison. OD indicates once daily; q1w, once weekly; q2w, every 2 weeks; q4w, every 4 weeks.
Figure 4.
Figure 4.. Forest Plots of Network Meta-analysis Results of Adults Treated Between 8 and 16 Weeks
Forest plots showing change in Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS). Results are presented for medications currently used in clinical practice or likely to be approved soon vs dupilumab on-label dosing (600 mg then 300 mg every 2 weeks). Results are presented as mean difference (MD) with 95% credible intervals (CrI). Positive values represent improvement in the disease state vs dupilumab. The vertical dashed lines represent the minimal clinically important difference for each scale. Authors can be contacted for relative effect estimates for all pairwise comparisons in the networks.
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