Upadacitinib superior to dupilumab in patients with moderate-to-severe AD

Treatment with upadacitinib demonstrated superior efficacy in achieving near-complete skin clearance and little to no itch at 16 weeks compared with dupilumab among adolescents and adults with moderate-to-severe atopic dermatitis (AD), according to the LEVEL UP study presented at EADV 2024.

At week 16, significantly more patients in the upadacitinib group achieved the primary composite endpoint of ≥90-percent reduction in Eczema Area and Severity Index (EASI90) and Worst Pruritus-Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) than the dupilumab group (19.9 percent vs 8.9 percent; p<0.0001). [EADV 2024, abstract 5385]

Similarly, upadacitinib showed superiority over dupilumab for all ranked secondary endpoints, particularly in achieving rapid onset of skin clearance (EASI90: 45.3 percent vs 26.3 percent; p<0.0001) and little to no itch (WP-NRS 0/1: 34.4 percent vs 18.8 percent; p<0.0001).

Of note, “the separation in the response of upadacitinib vs dupilumab was seen as early as week 1 for itching and week 2 for skin clearance,” said Dr Kilian Eyerich from the Department of Dermatology at George Washington University School of Medicine in Washington, DC, US, who presented the study on behalf of the investigators.

“Overall, the LEVEL UP study met the primary and all ranked secondary endpoints,” Eyerich noted.

The study is a head-to-head phase IIIb/IV trial, which analysed 920 patients (117 adolescents and 803 adults) with moderate-to-severe AD who had an inadequate response to systemic therapy or when the use of those therapies was inadvisable. Participants were randomized 1:1 to either upadacitinib 15 mg once daily as the starting dose, with a dose escalation to 30 mg once daily based on clinical response (n=458), or dupilumab per its label dose (n=462) for 16 weeks.

A cumulative dose escalation rate of nearly 70 percent was observed among patients receiving upadacitinib at week 12. Eyerich noted that 52 percent of patients treated with upadacitinib achieved the primary endpoint without increasing their dose, and 48 percent of patients who were escalated to 30 mg also achieved this outcome.

However, in terms of safety, adverse events (AEs) occurred more frequently in the upadacitinib arm vs the dupilumab arm (65.3 percent vs 52.7 percent), which was expected, said Eyerich.

The rates of serious AEs (0.9 percent for both) and AEs leading to treatment discontinuation (2 percent vs 1.3 percent) were similar between the upadacitinib and dupilumab arms, with no deaths reported in either treatment arm.

In addition, no malignancies, adjudicated major adverse cardiac events and venous thromboembolic events, or active tuberculosis were reported.

During the 16-week treatment period, the safety findings for upadacitinib and dupilumab were consistent with their known safety profiles, with no new safety signals identified, Eyerich noted.