516 - Comparative efficacy of targeted systemic therapies with topical corticosteroids for moderate-to-severe atopic dermatitis: an updated network meta-analysis
Bibliographic record
Abstract
Abstract Introduction Network meta-analysis (NMA) provides useful information for medical decision makers via comprehensive indirect comparisons across therapies. As the targeted systemic therapy options for moderate-to-severe atopic dermatitis (AD) continue to grow, it is critical to update NMAs as well. Objectives To assess the comparative efficacy of targeted systemic therapies with concomitant topical corticosteroids (TCS) in moderate-to-severe AD by including the latest Phase 3 combination therapy data for abrocitinib, lebrikizumab, and dupilumab in the NMA presented in Thyssen et al, 2021.1 Methods Data from the Phase 3 combination therapy trial for lebrikizumab in moderate-to-severe AD (ADhere [NCT04250337]) as well as an additional abrocitinib-dupilumab head-to-head Phase 3 trial (JADE DARE [NCT04345367]) were included in the analyses along with other eligible trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systematic literature review in Thyssen et al., 2021. Outcomes included ≥90% and ≥75% improvement in Eczema Area and Severity Index (EASI 90, EASI 75) from baseline, ≥4-point improvement in Pruritus Numerical Rating Scale from baseline (ΔNRS ≥4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with a ≥2-point reduction from baseline (IGA 0/1), at the week 16 timepoint of each study. Bayesian NMA was performed with fixed and random effects models, with and without baseline risk-adjustment; fit statistics were assessed. Inconsistency was assessed via unrelated mean relative effects models. Odds ratio (OR), number needed to treat (NNT), placebo-unadjusted absolute response rate (ARR), and Surface Under the Cumulative RAnking curve (SUCRA) scores were estimated. Statistical significance was assessed by OR 95% credible intervals excluding 1. Results The updated NMA analyzed 8 unique placebo-controlled trials and 1 active-controlled trial involving 4391 patients in 23 arms across 6 targeted therapies. Fit statistics supported fixed effects models across outcomes. All therapies were statistically more efficacious than placebo across all outcomes except baricitinib 2 mg for EASI-90. For EASI-90, upadacitinib 30 mg had the most favorable response estimates (ARR=63.2%, OR=11.3, NNT=2.0, SUCRA=98.3%), followed by abrocitinib 200 mg (ARR=55.8%, OR=8.3, NNT=2.4, SUCRA=90.0%), dupilumab 300 mg (ARR=44.8%, OR=5.3, NNT=3.2, SUCRA=68.3%), abrocitinib 100 mg (ARR=44.0%, OR=5.2, NNT=3.3, SUCRA=65.8%), upadacitinib 15 mg (ARR=42.9%, OR=4.9, NNT=3.4, SUCRA=64.3%), and the newly added lebrikizumab 250 mg (ARR=28.9%, OR=2.7, NNT=6.6, SUCRA=39.9%). The rank order for EASI-75 was similar (upadacitinib 30 mg [ARR=78.3%, OR=9.5, NNT=2.0, SUCRA=98.5%], abrocitinib 200 mg [ARR=73.0%,OR=7.1, NNT=2.3, SUCRA=89.1%], upadacitinib 15 mg [ARR=66.1%, OR=5.1, NNT=2.7, SUCRA=71.0%], dupilumab 300 mg [ARR=65.3%, OR=5.0, NNT=2.7, SUCRA=69.2%], abrocitinib 100 mg [ARR=60.3%, OR=4.0, NNT=3.2, SUCRA=54.0%], and lebrikizumab 250 mg [ARR=54.5%, OR=3.1, NNT=3.8, SUCRA=41.2%]). For ΔNRS ≥4, upadacitinib 30 mg had the most favorable response (ARR=68.9%, OR=10.0, NNT=2.1, SUCRA=99.9%), followed by upadacitinib 15 mg (ARR=56.6%, OR=5.9, NNT=2.7, SUCRA=84.0%), abrocitinib 200 mg (ARR=51.6%, OR=4.8, NNT=3.1, SUCRA=75.6%), dupilumab 300 mg (ARR=49.3%, OR=4.4, NNT=3.3, SUCRA=67.0%), baricitinib 4 mg (ARR=44.4%, OR=3.6, NNT=4.0, SUCRA=57.7%), and abrocitinib 100 mg (ARR=35.9%, OR=2.5, NNT=5.9, SUCRA=36.1%); lebrikizumab 250 mg ranked eighth (ARR=33.4%, OR=2.3, NNT=7.0, SUCRA=31.3%). For IGA 0/1, upadacitinib 30 mg (ARR=66.5%,OR=11.7, NNT=2.0, SUCRA=99.6%) had the most favorable estimates, followed by abrocitinib 200 mg (ARR=53.5%, OR=6.8, NNT=2.6, SUCRA=86.6%), upadacitinib 15 mg (ARR=48.0%, OR=5.4, NNT=3.0, SUCRA=76.2%), dupilumab 300 mg (ARR=42.1%, OR=4.3, NNT=3.7, SUCRA=64.7%), abrocitinib 100 mg (ARR=39.1%, OR=3.8, NNT=4.1, SUCRA=56.1%), and baricitinib 4 mg (ARR=30.6%, OR=2.6, NNT=6.4, SUCRA=39.9%); lebrikizumab 250 mg ranked seventh (ARR=29.2%, OR=2.4, NNT=7.0, SUCRA=35.8%). Baricitinib 2 mg and tralokinumab 300 mg were generally ranked lower across outcomes. Conclusions Among targeted therapies for moderate-to-severe AD used with concomitant TCS for 16 weeks, upadacitinib 30 mg remained the most efficacious therapy in this NMA, generally followed by abrocitinib 200 mg, upadacitinib 15 mg or dupilumab 300 mg, abrocitinib 100 mg, and baricitinib 4 mg or lebrikizumab 250 mg.
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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 | 0.027 | 0.059 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.051 |
| Bibliometrics | 0.005 | 0.005 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".