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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. 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. [ABSTRACT FROM AUTHOR]

The landscape of targeted systemic treatments for moderate-to-severe atopic dermatitis (AD) continues to expand. With limited head-to-head randomized controlled trials conducted in AD, a network meta-analysis (NMA) helps inform treatment decisions by providing indirect comparisons across therapies. This study aims to update an NMA presented in Silverberg et al. (2022), assessing the comparative efficacy of targeted systemic treatments without concomitant topical corticosteroids in moderate-to-severe AD by including the latest Phase 3 monotherapy data for lebrikizumab. Data from the two most recently published Phase 3 monotherapy trials for lebrikizumab in moderate-to-severe AD [ADvocate1 (NCT04146363); ADvocate2 (NCT04178967)] were included in the analyses along with other eligible Phase 3 or 4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib identified through a systemic literature review in Silverberg et al. (2022). Prespecified efficacy 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 primary endpoint timepoint for each study (Week 12 for abrocitinib, Week 16 for all other therapies). Bayesian NMA was performed with fixed-effect, random-effect and baseline risk-adjusted models; fit statistics and diagnostics were assessed. The 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. The updated NMA analysed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across six targeted therapies. Fit statistics and diagnostics supported fixed-effect models for all outcomes analysed. All targeted therapies had significantly greater response rates compared with placebo across all outcomes. For EASI 90, upadacitinib 30 mg had the most favorable response estimates (ARR = 58.3%, OR = 23.1, NNT = 1.9, SUCRA = 98.5%), followed by abrocitinib 200 mg (ARR = 45.2%, OR = 13.5, NNT = 2.5, SUCRA = 84.3%), upadacitinib 15 mg (ARR = 43.7%, OR = 12.8, NNT = 2.6, SUCRA = 82.0%), dupilumab 300 mg (ARR = 27.3%, OR = 6.2, NNT = 4.7, SUCRA = 52.8%), abrocitinib 100 mg (ARR = 26.8%, OR = 6.0, NNT = 4.8, SUCRA = 48.4%), baricitinib 4 mg (ARR = 25.0%, OR = 5.5, NNT = 5.2, SUCRA = 45.5%) and lebrikizumab 250 mg (ARR = 23.6%, OR = 5.1, NNT = 5.6, SUCRA = 40.0%). A similar rank order was observed for EASI 75 [upadacitinib 30 mg (ARR = 72.3%, OR = 19.1, NNT = 1.7, SUCRA = 98.5%), abrocitinib 200 mg (ARR = 64.6%, OR = 13.3, NNT = 1.9, SUCRA = 87.3%), upadacitinib 15 mg (ARR = 59.8%, OR = 10.9, NNT = 2.1, SUCRA = 80.2%), dupilumab 300 mg (ARR = 45.3%, OR = 6.0, NNT = 3.0, SUCRA = 55.4%), abrocitinib 100 mg (ARR = 44.9%, OR = 5.9, NNT = 3.1, SUCRA = 53.5%) and lebrikizumab 250 mg (ARR = 44.7%, OR = 5.9, NNT = 3.1, SUCRA = 53.9%)]. For ΔNRS ≥4, upadacitinib 30 mg also had the most favorable response (ARR = 56.1%, OR = 12.9, NNT = 2.1, SUCRA = 99.0%), followed by abrocitinib 200 mg (ARR = 45.4%, OR = 8.3, NNT = 2.8, SUCRA = 83.6%), upadacitinib 15 mg (ARR = 42.9%, OR = 7.6, NNT = 3.0, SUCRA = 79.2%), dupilumab 300 mg (ARR = 33.9%, OR = 5.2, NNT = 4.0, SUCRA = 54.2%), lebrikizumab 250 mg (ARR = 33.9%, OR = 5.1, NNT = 4.1, SUCRA = 54.1%) and abrocitinib 100 mg (ARR = 31.5%, OR = 4.6, NNT = 4.5, SUCRA = 46.1%). For IGA 0/1, upadacitinib 30 mg (ARR = 61.8%, OR = 19.4, NNT = 1.9, SUCRA = 99.9%) and upadacitinib 15 mg (ARR = 48.1%, OR = 11.1, NNT = 2.5, SUCRA = 86.9%) had the most favorable estimates, followed by abrocitinib 200 mg (ARR = 39.3%, OR = 7.7, NNT = 3.2, SUCRA = 75.5%), dupilumab 300 mg (ARR = 32.4%, OR = 5.7, NNT = 4.1, SUCRA = 62.1%) and lebrikizumab 250 mg (ARR = 28.0%, OR = 4.7, NNT = 5.0, SUCRA = 49.1%). Baricitinib 2 mg and tralokinumab 300 mg were generally ranked lower across outcomes. Among targeted treatments for moderate-to-severe AD used without concomitant topical corticosteroids for 12–16 weeks, upadacitinib 30 mg remains the most efficacious therapy in this NMA, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg and lebrikizumab 250 mg or abrocitinib 100 mg. [ABSTRACT FROM AUTHOR]