524 - Efficacy of upadacitinib and dupilumab on achieving stringent and composite skin and itch outcomes: an indirect comparison of adults with moderate-to-severe atopic dermatitis

Abstract

Abstract Introduction/Background Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and Measure Up 2 assessed efficacy of upadacitinib 30mg and upadacitinib 15mg against placebo, while Heads Up assessed efficacy of upadacitinib 30mg in a head-to-head trial against dupilumab 300mg. Network meta-analysis has shown that upadacitinib 30mg and upadacitinib 15mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated stringent and composite measures of efficacy. Objectives To indirectly compare upadacitinib and dupilumab on stringent and composite measures of skin clearance and itch resolution. Methods A population-adjusted indirect comparison using covariate adjustment as a treatment effect calibration was conducted using individual patient data from Measure Up 1 and 2 and Heads Up. Specifically, the indirect comparison model estimated how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates (age, gender, race, country, previous use of systemic therapy, disease duration, baseline validated Investigator Global Assessment scale for AD score, and baseline Eczema Area and Severity Index [EASI]). Absolute response rates at weeks 4 and 16 were estimated for the following outcomes: no/minimal itch (Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1), 100% improvement in EASI (EASI 100), achievement of both ≥90% improvement in EASI (EASI 90) and WP-NRS 0/1, and achievement of both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to-treat population for the clinical trials, and utilized non-responder imputation. Results Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg, and then dupilumab. This pattern was observed at week 4 on the achievement of WP-NRS 0/1 (upadacitinib 30 mg: 34.2% | upadacitinib 15 mg: 18.2% | dupilumab: 7.9%), EASI 100 (8.5% | 4.7% | 1.8%), EASI 90 & WP-NRS 0/1 (21.9% | 10.6% | 3.3%), and EASI 100 & WP-NRS 0/1 (6.4% | 3.5% | 1.2%). This ranking was maintained at week 16 for WP-NRS 0/1 (35.4% | 22.5% | 16.2%), EASI 100 (28.4% | 22.2% | 7.9%), EASI 90 & WP-NRS 0/1 (32.2% | 19.6% | 12.4%), and EASI 100 & WP-NRS 0/1 (19.6% | 12.7% | 4.2%). Conclusions For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining stringent and composite outcomes after 4 and 16 weeks, followed by upadacitinib 15 mg, and then dupilumab.