(A-048) Dupilumab Demonstrates a Higher Benefit-risk Score Compared with Upadacitinib: A Structured Benefit-risk Assessment of the HEADS UP Trial

Background: Treatment comparisons often focus on single outcomes at specific times. However, healthcare professionals weigh benefits and risks during joint decision-making with patients. No structured benefit-risk assessments for atopic dermatitis treatments have been published.

Objectives: To evaluate the benefit-risk of dupilumab vs upadacitinib using a quantitative approach based on head-to-head comparison data from the HEADS UP trial (NCT03738397).

Methods: Benefits and risks of systemic treatments relevant to adult patients (aged ≥18 years) with AD were identified from an independent patient preference study using a discrete choice experiment that measures the benefit and risk outcome of a given drug and their relative importance. The respective outcomes from the HEADS UP trial were assessed for the identified key benefits and risks. A quantitative benefit-risk assessment using multicriteria decision analysis was conducted using Hiview 3.2 software, a validated program for benefit-risk assessment. The benefit-risk score (scale: 0–100) measured the overall performance of the AD treatments as the weighted sum of values of the selected outcomes. Value functions were estimated using confidence intervals obtained from trial and published. To test the robustness of the results, a sensitivity analysis was conducted varying the total weight attributed to the benefits.

Results: Patient preference scores of the key benefits (improvement in itch, 16.0%; improvement in skin clearance, 24.2%; time to itch response, 7.4%; frequency and mode of administration, 14.4%) and key risks (avoidance of severe side effects, 31.2%; avoidance of monitoring due to the risk of adverse events, 6.8%) were derived from the independent patient preference study. Dupilumab had an overall benefit-risk score of 66 compared with a score of 61 for upadacitinib. Individual score components indicate similar results between treatments except for avoidance of severe risks (dupilumab, 17.2; upadacitinib, 2.8) and time to itch response (dupilumab, 3.4; upadacitinib, 6.9). Based on a sensitivity analysis, the overall benefit-risk score of dupilumab is consistently better than that of upadacitinib, unless patient preferences for benefits exceed preferences for a better risk profile by >2.

Conclusions: When considering all key benefits and risks in this assessment, dupilumab demonstrated a higher benefit-risk score compared with upadacitinib. This assessment reinforces dupilumab as a preferred first-line treatment option for patients with moderate-to-severe AD. The data may help HCPs weigh the benefits and risks between various drug classes when making informed treatment decisions for their patients with AD.