TY - JOUR
T1 - Comparing binary efficacy outcomes for systemic immunomodulatory treatments for atopic dermatitis in a living systematic review and network meta-analysis
AU - Drucker, Aaron M
AU - Lam, Megan
AU - Elsawi, Rawaan
AU - Prieto-Merino, David
AU - Malek, Rayka
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 - © The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.
PY - 2023/12/6
Y1 - 2023/12/6
N2 - BACKGROUND: Systemic treatments for atopic dermatitis are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis, we previously analyzed continuous efficacy measures.OBJECTIVE: To compare binary efficacy outcomes of systemic treatments for atopic dermatitis.METHODS: We searched 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 through November 7, 2022. We included randomized trials examining ≥8 weeks of treatment with systemic immunomodulatory medications for moderate-severe atopic dermatitis. We screened titles, abstracts, and full texts and abstracted data independently in duplicate. Outcomes included the proportion of patients achieving 50%, 75% and 90% improvement in Eczema Area and Severity Index (EASI-50, -75, -90) and Investigator Global Assessment (IGA) success. We performed random-effects Bayesian network meta-analyses to calculate odds ratios (OR) and 95% credible intervals (CrI) between each intervention for each outcome.RESULTS: 83 trials with 22,122 participants are included in the systematic review. In analyses limited to trials of 8-16 weeks duration with predominantly adult populations, abrocitinib 200 mg daily (OR 1.5, 95% CrI 1.1 to 2.2) and upadacitinib 15 mg daily (OR 1.7, 95% CrI 0.9 to 3.3) and 30 mg daily (OR 2.5, 95% CrI 1.3 to 5.0) were associated with higher odds of achieving EASI-50 compared to dupilumab. Abrocitinib 100 mg daily (OR 0.7, 95% CrI 0.5 to 1.0), baricitinib 2 mg daily (OR 0.4, 95% CrI 0.3 to 0.5) and 4 mg daily (OR 0.5, 95% CrI 0.3 to 0.7) and tralokinumab (OR 0.4, 95% CrI 0.3 to 0.6) were associated with lower odds of achieving EASI-50 compared to dupilumab. Results were similar for EASI-75, EASI-90 and IGA success.CONCLUSIONS: Supporting results for continuous measures, upadacitinib 30 mg daily and abrocitinib 200 mg daily are the most efficacious with regards to binary efficacy endpoints up to 16 weeks in adults, followed by upadacitinib 15 mg daily, dupilumab and abrocitinib 100 mg daily. Dupilumab and both doses of upadacitinib and abrocitinib are more efficacious than baricitinib 4 and 2 mg daily and tralokinumab.REGISTRATION: PROSPERO CRD42018088112.
AB - BACKGROUND: Systemic treatments for atopic dermatitis are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis, we previously analyzed continuous efficacy measures.OBJECTIVE: To compare binary efficacy outcomes of systemic treatments for atopic dermatitis.METHODS: We searched 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 through November 7, 2022. We included randomized trials examining ≥8 weeks of treatment with systemic immunomodulatory medications for moderate-severe atopic dermatitis. We screened titles, abstracts, and full texts and abstracted data independently in duplicate. Outcomes included the proportion of patients achieving 50%, 75% and 90% improvement in Eczema Area and Severity Index (EASI-50, -75, -90) and Investigator Global Assessment (IGA) success. We performed random-effects Bayesian network meta-analyses to calculate odds ratios (OR) and 95% credible intervals (CrI) between each intervention for each outcome.RESULTS: 83 trials with 22,122 participants are included in the systematic review. In analyses limited to trials of 8-16 weeks duration with predominantly adult populations, abrocitinib 200 mg daily (OR 1.5, 95% CrI 1.1 to 2.2) and upadacitinib 15 mg daily (OR 1.7, 95% CrI 0.9 to 3.3) and 30 mg daily (OR 2.5, 95% CrI 1.3 to 5.0) were associated with higher odds of achieving EASI-50 compared to dupilumab. Abrocitinib 100 mg daily (OR 0.7, 95% CrI 0.5 to 1.0), baricitinib 2 mg daily (OR 0.4, 95% CrI 0.3 to 0.5) and 4 mg daily (OR 0.5, 95% CrI 0.3 to 0.7) and tralokinumab (OR 0.4, 95% CrI 0.3 to 0.6) were associated with lower odds of achieving EASI-50 compared to dupilumab. Results were similar for EASI-75, EASI-90 and IGA success.CONCLUSIONS: Supporting results for continuous measures, upadacitinib 30 mg daily and abrocitinib 200 mg daily are the most efficacious with regards to binary efficacy endpoints up to 16 weeks in adults, followed by upadacitinib 15 mg daily, dupilumab and abrocitinib 100 mg daily. Dupilumab and both doses of upadacitinib and abrocitinib are more efficacious than baricitinib 4 and 2 mg daily and tralokinumab.REGISTRATION: PROSPERO CRD42018088112.
UR - https://www.mendeley.com/catalogue/cff0bd72-9980-3dd1-990f-4f7dfb4099f2/
U2 - 10.1093/bjd/ljad393
DO - 10.1093/bjd/ljad393
M3 - Article
C2 - 37831594
SN - 0007-0963
JO - The British journal of dermatology
JF - The British journal of dermatology
M1 - ljad393
ER -