Atopic dermatitis (AD) patients who switched to upadacitinib (Rinvoq, AbbVie) from dupilumab (Dupixent, Regeneron, and Sanofi) hit higher treatment targets, according to results from Period 2 of the LEVEL UP study presented at the 2024 Fall Clinical Dermatology Conference in Las Vegas, NV.
“At a big picture level, Period 2 data tells us what happens when dermatology providers switch a patient from a biologic therapy that is not meeting a moderate treatment target (EASI-75) to an oral JAK inhibitor,” says Christopher Bunick, MD, PhD, an Associate Professor of Dermatology at Yale University in New Haven, CT. “More specifically, Period 2 data informs us how patients on dupilumab who fail to meet EASI-75 at Week 16, a moderate treatment target, improve when switched to upadacitinib 15mg once daily.”
Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor-blinded, head-to-head, multi-center study evaluating upadacitinib vs. dupilumab in adolescents and adults with moderate-to-severe AD who had an inadequate response to systemic therapy or when the use of those therapies was inadvisable.
Learn more about LEVEL UP, the first head-to-head trial in AD assessing upadacitinib (Rinvoq, AbbVie) at a starting dose of 15mg daily vs. dupilumab (Dupixent, Sanofi and Regeneron Pharmaceuticals) at its labeled dose, in Raising the Bar in Atopic Dermatitis (AD): Unpacking the practice-changing implications of the LEVEL-Up study in AD.
Unpacking LEVEL UP Period 2 Data
Three hundred and fifty-five patients entered Period 2 of the study, of which 208 received dupilumab in Period 1 and switched to upadacitinib in Period 2, and 147 continued with upadacitinib. In the switchers, 47.6% of patients escalated to upadacitinib 30mg in Period 2, and 52.4% were never dose escalated.
Of those patients who switched from dupilumab to upadacitinib, 79.6%, 58.7%, and 19.9% achieved an Eczema Area and Severity Index (EASI) 75, 90, and 100, respectively. Response was seen as early as 4 weeks post-switch (Week 20), with increased responses by 16 weeks post-switch (Week 32).
Patients who switched to upadacitinib from dupilumab also showed improvements in measures of itch. Most achieved ≥ 4-point improvement in the Worst Pruritus Numerical Rating Scale (WP-NRS) by Week 20, with a greater proportion reaching this endpoint at Week 32. The study found that the proportion of patients achieving WP-NRS 0/1 increased by 4 weeks post-switch (Week 20), with additional increases by Week 32.
Fully 26.8% of patients reached both EASI 90 and WP-NRS 0/1 by 16 weeks post-switch from dupilumab to upadacitinib (Week 20, Week 32), with response rates seen as early as four weeks post-switch. Week 20 results include patients on 15mg upadacitinib, as dose escalations did not occur until Week 20 or later if protocol criteria were met. Week 32 results include patients on upadacitinib 15mg and those who dose escalated to 30mg. Efficacy measures for patients in the group who remained on upadacitinib indicated that a proportion of patients achieved clinically meaningful improvements in both skin and itch outcomes after continuing treatment.
In Period 2 of Level Up, the switch occurred from biologic to JAK inhibitor at Week 16 when dupilumab did not hit the moderate treatment target of EASI-75,” Dr. Bunick explains. “Week 16 represents the time of attaining steady-state concentration of the biologic in plasma. No washout period was necessary, as in the real-world patients will be and can be safely switched without delay to upadacitinib from dupilumab or another biologic.”
Both groups had similar proportions of patients with treatment-emergent adverse events (TEAEs). The most frequently reported TEAEs included nasopharyngitis, acne, upper respiratory tract infection, and atopic dermatitis. No new safety signals were observed after switching to upadacitinib from dupilumab without a washout period
“If a patient is on a biologic and not achieving at least a moderate treatment target of EASI-75 by Week 16, then the LEVEL-UP Period 2 data indicates the patient should be switched to another advanced systemic therapy like the oral JAK inhibitor upadacitinib,” Dr. Bunick says. “The week 16 or 4-month strategy is consistent with overcoming therapeutic inertia, which is the tendency for patients to remain on sub-optimal treatments for their atopic dermatitis longer than they should.”
