Upadacitinib 30 mg Tops Atopic Dermatitis Systemic Therapies in Meta-Analyses

Jonathan Silverberg, MD, PhD, MPH

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Upadacitinib 30 mg may provide the best efficacy among various systemic therapy regimens for the treatment of moderate to severe atopic dermatitis without topical corticosteroids, according to new data from a recent analysis.¹

In findings from an updated network meta-analysis presented at the Revolutionizing Atopic Dermatitis (RAD) 2023 Spring Conference in Washington, DC, this weekend, a team of dermatology investigators reported that the 30 mg dose of the AbbVie Janus kinase (JAK) inhibitor is associated with a patient greater response rate per high-efficacy Eczema Area Severity Index (EASI) scores than comparative systemic therapies including abrocitinib, dupilumab, and more.

The outcomes from the updated network meta-analysis originally presented in 2022 help provide clinician guidance on hierarchal atopic dermatitis efficacy for systemic therapies administered without concomitant corticosteroids.

Led by Jonathan I. Silverberg, MD, PhD, MPH, of the department of dermatology at The George Washington University School of Medicine and Health Sciences, investigators provided an update to the previously presented network-meta analysis at RAD 2023 with consideration to recently published phase 3 monotherapy data for lebrikizumab. Their work was funded by AbbVie.

Interpreting comparative efficacy outcomes among the available systemic therapies as primary methods of atopic dermatitis treatment is a key priority for prescribing clinicians who are now navigating a bevvy of proven agents across the JAK inhibitor, biologic and other drug classes.

“The landscape of targeted systemic treatments for moderate-to-severe atopic dermatitis continues to expand,” Silverberg and colleagues wrote. “With limited head-to-head randomized controlled trials conducted in atopic dermatitis, a network meta-analysis (NMA) helps inform treatment decisions by providing indirect comparisons across therapies.”

The full analyses including eligible phase 3 or 4 randomized, placebo-controlled trials assessing a number of systemic therapy regimens for patients with moderate to severe atopic dermatitis:

• Abrocitinib 100 mg
• Abrocitinib 200 mg
• Baricitinib 4 mg
• Dupilumab 300 mg
• Lebrikizumab 250 mg
• Upadacitinib 15 mg
• Upadacitinib 30 mg

The investigators reviewed a series of prespecified efficacy outcomes from baseline to 12-16 weeks from the available literature, including the following:

• EASI 75
• EASI 90
• Investigator Global Assessment (IGA) 0 or 1
• ≥2 point reduction in IGA
• ≥4 point improvement in Pruritus Numerical Rating Scale (NRS ≥4)

The team additionally calculated odds ratio (OR), number needed to treat (NNT) and absolute response rates (ARRs) adjusted for placebo outcomes for each efficacy outcome. The analysis included 7105 patients treated in 32 arms across 6 systemic therapies in 13 unique placebo-controlled trials.

Silberberg and colleagues observed significantly greater response rates versus placebo across all prespecified outcomes. Upadacitinib 30 mg provided the greatest estimated response per EASI 90 (ARR, 58.3%; OR, 23.1; NNT, 1.9) as well as EASI 75 (ARR, 72.3%; OR, 19.1; NNT, 1.7) among all observed regimens. Abrocitinib 200 mg provided the second-greatest estimated efficacy for each outcome (ARR, 45.2%; 64.6%, respectively), followed by upadacitinib 15 mg.

Upadacitinib 30 mg additionally had the greatest estimated response per NRS ≥4 (ARR, 56.1%; OR, 12.9; NNT, 2.1) followed by abrocitinib 200 mg, upadacitinib 15 mg, and dupilumab 300 mg. Both doses of upadacitinib were estimated to have the greatest IGA 0/1 response among treated patients (30 mg ARR, 61.8%; OR, 19.4; NNT, 1.9), followed by abrocitinib 200 mg and dupilumab 300 mg.

The team noted that baricitinib 2 mg and tralokinumab 300 mg were generally among the lower-ranked regimens across the observed efficacy outcomes.

Investigators concluded their findings show a hierarchy of efficacy in monotherapy systemic agents treating moderate to severe atopic dermatitis: upadacitinib 30 mg, then abrocitinib 200 mg; upadacitinib 15 mg; dupilumab 300 mg; and lebrikizumab 250 mg or abrocitinib 100 mg.

“Among targeted treatments for moderate-to-severe atopic dermatitis used without concomitant topical corticosteroids for 12 to 16 weeks, upadacitinib 30 mg remains the most efficacious therapy based on findings from this network meta-analysis,” they wrote.

References

1. ^{Silverberg J, Hong H, Thyssen J, Calimlim B, et al. Comparative efficacy of targeted systemic therapies for moderate-to-severe atopic dermatitis without topical corticosteroids: an updated network meta-analysis. Paper presented at: Revolutionizing Atopic Dermatitis 2023; April 29 – May 1, 2023; Washington, DC. Accessed April 30, 2023.}