Upadacitinib Tops Nemolizumab on Skin, Itch Targets in Indirect Analysis

Upadacitinib (Rinvoq) treatment at 15 mg and 30 mg produces higher placebo-adjusted response rates than nemolizumab (Nemluvio) across skin and itch treatment targets through Week 16 in adults and adolescents with moderate to severe atopic dermatitis receiving background topical corticosteroids, according to a matching-adjusted indirect comparison.¹

This was presented at the 2026 European Academy of Dermatology and Venereology (EADV) Congress.¹ The AbbVie-funded analysis, first presented at the Revolutionizing Atopic Dermatitis (RAD) Conference in June 2026, was led by Jonathan I. Silverberg, MD, PhD, MPH, of George Washington University School of Medicine and Health Sciences. The findings were presented as Poster P1668. No head-to-head trial has compared the oral Janus kinase 1 inhibitor with the interleukin 31 receptor alpha antagonist.¹

How Did Investigators Compare Upadacitinib and Nemolizumab?

The team used individual patient data from the phase 3 AD Up trial (NCT03568318), in which patients received upadacitinib 15 mg, upadacitinib 30 mg, or placebo with topical corticosteroids for 16 weeks.¹˒² Because patient-level nemolizumab data were unavailable, investigators relied on published aggregate results from the phase 3 ARCADIA 1 and 2 trials of nemolizumab 30 mg.¹˒³

Upadacitinib patients were weighted to mirror nemolizumab trial populations on disease severity scores, age, weight, sex, race, and quality of life. All trials required an EASI score of 16 or higher, at least 10% body surface area, and a Worst Pruritus Numerical Rating Scale (WP-NRS) score of 4 or higher.¹

Outcomes followed the Aiming High in Eczema/Atopic Dermatitis (AHEAD) framework. Moderate targets included EASI-75, a WP-NRS improvement of 4 points or more, and both combined, while optimal targets were EASI-90 and a WP-NRS score below 2. Comparisons relied on placebo-adjusted risk differences with nonresponder imputation.¹

What Did the Indirect Comparison Show?

Before placebo adjustment, matching-adjusted EASI-75 rates at Week 16 were 68.3% with upadacitinib 15 mg and 79.2% with upadacitinib 30 mg, compared with 42.9% reported for nemolizumab in ARCADIA.¹

At the 16-week mark, placebo-adjusted EASI-75 response reached 40.8 percentage points with upadacitinib 15 mg and 51.8 points with upadacitinib 30 mg, compared with 13.4 points with nemolizumab. For EASI-90, the corresponding values were 33.7, 54.9, and 8.0 points.¹

Itch outcomes followed a similar pattern. Placebo-adjusted rates for a WP-NRS improvement of at least 4 points were 40.4 and 48.6 points with the 2 upadacitinib doses versus 24.0 points with nemolizumab, and rates for a WP-NRS score below 2 were 31.4 and 42.2 points versus 18.3 points.¹

For the combined skin and itch target, placebo-adjusted response was 36.2 and 48.5 points with upadacitinib versus 12.8 points with nemolizumab. Risk differences favored both upadacitinib doses across all 5 outcomes (P < .001).¹

Significant differences favoring upadacitinib appeared by Week 2 for both itch endpoints and by the fourth week for EASI-75, EASI-90, and the combined skin and itch target. These differences held at every subsequent assessment through Week 16.¹

What Limitations Should Clinicians Consider?

Patients in the ARCADIA trials could use topical calcineurin inhibitors alongside corticosteroids and completed a topical run-in period before baseline, both of which the authors acknowledged could bias results. Indirect comparisons also cannot account for unmeasured differences between trial populations.¹

The WP-NRS score below 2 endpoint was derived specifically for this analysis to match ARCADIA reporting, since AD Up originally reported WP-NRS 0/1. AbbVie funded the study, and several authors are company employees.¹

Editor’s note: This summary has been edited for grammar and clarity using artificial intelligence tools.

References

1. Silverberg JI, Bunick CG, Chovatiya R, et al. Comparative efficacy of upadacitinib and nemolizumab in combination with background topical therapy in adults and adolescents with moderate-to-severe atopic dermatitis: a placebo-anchored matching-adjusted indirect comparison. Poster P1668. Presented at: 2026 European Academy of Dermatology and Venereology Congress; September 30-October 3, 2026; Vienna, Austria.

2. Silverberg JI, et al. J Allergy Clin Immunol. 2022;143(3):977-987.

3. Silverberg JI, et al. Lancet. 2024;404(10451):445-460.