Comparing binary efficacy outcomes for systemic immunomodulatory treatments for atopic dermatitis in a living systematic review and network meta-analysis
Bibliographic record
Abstract
BACKGROUND: Systemic treatments for atopic dermatitis (AD) are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis (NMA), we previously analysed continuous efficacy measures. OBJECTIVES: To compare binary efficacy outcomes of systemic treatments for AD. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American and Caribbean Health Science Information (LILACS) database, Global Resource for Eczema Trials (GREAT) database and trial registries up to 1 March 2023. We included randomized trials examining ≥ 8 weeks of treatment with systemic immunomodulatory medications for moderate-to-severe AD. We screened titles, abstracts and full texts and abstracted data independently, in duplicate. Outcomes included the proportion of patients achieving at least 50%, 75% and 90% improvements in Eczema Area and Severity Index (EASI 50, EASI 75 and EASI 90, respectively) and Investigator Global Assessment (IGA) success. We performed random-effects Bayesian NMAs to calculate odds ratios (OR) and 95% credible intervals (CrIs) between each intervention for each outcome. RESULTS: Eighty-three trials with 22 122 participants were 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 1.1-2.2) and upadacitinib 15 mg daily (OR 1.7, 95% CrI 0.9-3.3) and 30 mg daily (OR 2.5, 95% CrI 1.3-5.0) were associated with higher odds of achieving EASI 50 vs. dupilumab. Abrocitinib 100 mg daily (OR 0.7, 95% CrI 0.5-1.0), baricitinib 2 mg daily (OR 0.4, 95% CrI 0.3-0.5) and 4 mg daily (OR 0.5, 95% CrI 0.3-0.7), and tralokinumab (OR 0.4, 95% CrI 0.3-0.6) were associated with lower odds of achieving EASI 50 vs. dupilumab. Results were similar for EASI 75, EASI 90 and IGA success. CONCLUSIONS: Supporting results for continuous outcome measures, upadacitinib 30 mg daily and abrocitinib 200 mg daily are the most efficacious with regard to binary efficacy endpoints up to 16 weeks in adults with moderate-to-severe AD, 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.045 | 0.111 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.023 | 0.045 |
| Bibliometrics | 0.013 | 0.010 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.005 | 0.003 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".