Upadacitinib Shows Superiority to Dupilumab for Atopic Dermatitis With Dose Escalation

When initiated at a 15 mg dose and escalated to 30 mg based on clinical response, upadacitinib (Rinvoq; AbbVie) showed superiority compared with dupilumab (Dupixent; Sanofi, Regeneron), achieving Eczema Area and Severity Score (EASI) 90 and Worst Pruritus Numerical Rating Scale (WP-NRS) 0/1 at week 16, according to data from the LEVEL UP trial.

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According to the presentation, upadacitinib and dupilumab are approved in multiple countries to treat moderate-to-severe atopic dermatitis (AD) in adolescents and adults, though the indications for upadacitinib differ, with some countries recommending 15 mg as the starting dose then escalating to 30 mg if necessary. In the Heads Up study, investigators evaluated the efficacy and safety of upadacitinib in the 30 mg dosage, but not the 15 mg dosage. Therefore, in this study, investigators aimed to evaluate the efficacy and safety of upadacitinib when initiated at the 15 mg dosage and escalated to 30 mg based on clinical response.

The primary endpoint was the simultaneous achievement of EASI 90 and NRS 0/1 at week 16. Although the study is still ongoing, investigators presented the week 16 primary analysis results in June. The trial is a phase 3b/4 randomized, open-label, blinded, multicenter study that evaluated the 2 drugs in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use of the therapies was not advised.

Treatment was randomized for patients, with either upadacitinib 15 mg or dupilumab as per its label for 16 weeks. There was a 16-week extension period for patients who did not achieve at least a 75% reduction in EASI 75 at the conclusion of the study. Investigators escalated the dose to upadacitinib 30 mg at week 4 if the patient had less than a EASI 50 response or less than a 4-point improvement from baseline to WP-NRS scores. Furthermore, individuals were dose-escalated if they did not achieve EASI 75 at week 8.

There were a total of 920 individuals included in the study, with 458 taking upadacitinib and 462 taking dupilumab. Approximately 44.8% were female and 63.6% were aged 18 to 39. There was a mean EASI of 27.4 and a body surface area mean of 38.2 at baseline.

The results of the study showed that the primary end point started as early as 4 weeks and was maintained through week 16. For secondary end points, upadacitinib demonstrated superiority compared with dupilumab in achievement of EASI 75, 90, and 100 as well as superiority in these scores at each study visit through week 16. Furthermore, at weeks 2, 4, and 15 upadacitinib showed superiority to dupilumab in WP-NRS 0/1 score as well as at each study visit through week 16. This superiority started as early as week 1 and maintained through week 16.

Investigators reported that there was a higher proportion of overall treatment-emergent adverse events (AEs) for upadacitinib (65.3%) compared with dupilumab (52.7%), but serious AEs (0.9% vs 0.9%, respectively) and AEs leading to discontinuation (2% vs 1.3%, respectively) were similar between groups.

The most common treatment-related AEs with upadacitinib included elevated creatine phosphokinase, hepatic disorder, herpes zoster, opportunistic infection (excluding tuberculosis and herpes zoster), anemia, neutropenia, and lymphopenia, according to the presentation.

Reference

Silverberg JI, Bunick C, Hong C, Mendes-Bastos P, et al. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults and Adolescents with Moderate-to- Severe Atopic Dermatitis: Results of an Openlabel, Efficacy Assessor-Blinded Head-to-Head Phase 3b/4 Study (Level Up). Presented at: Revolutionizing Atopic Dermatitis Conference. Chicago, Illinois. June 8 to June 10, 2024.