TY - JOUR
T1 - Systemic Immunomodulatory Treatments for Atopic Dermatitis
T2 - Update of a Living Systematic Review and Network Meta-analysis
AU - Drucker, Aaron M.
AU - Morra, Deanna E.
AU - Prieto-Merino, David
AU - Ellis, Alexandra G.
AU - Yiu, Zenas Z.N.
AU - Rochwerg, Bram
AU - Di Giorgio, Sonya
AU - Arents, Bernd W.M.
AU - Burton, Tim
AU - Spuls, Phyllis I.
AU - Schmitt, Jochen
AU - Flohr, Carsten
N1 - Funding Information:
Funding/Support: This work was supported
Funding Information:
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.
Publisher Copyright:
© 2022 Drucker AM et al. JAMA Dermatology.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85127537354&partnerID=8YFLogxK
U2 - 10.1001/jamadermatol.2022.0455
DO - 10.1001/jamadermatol.2022.0455
M3 - Article
C2 - 35293977
AN - SCOPUS:85127537354
SN - 2168-6068
VL - 158
SP - 523
EP - 532
JO - JAMA dermatology
JF - JAMA dermatology
IS - 5
ER -