A Patient Preference-Weighted Quantitative Benefit-Risk Analysis of Ritlecitinib for Alopecia Areata to Inform Medical Decision Making.

Abstract

Objectives: Inhibition of JAK-mediated signaling pathways leads to hair regrowth and improved quality of life in alopecia areata (AA) but may be associated with potential risks. This study assessed the benefit-risk profile of ritlecitinib, an oral selective JAK3/TEC family kinase inhibitor (JAK3/TEC), from the perspective of adult patients with AA to inform regulatory decisions.

Methods: We combined patient preference data from a discrete choice experiment (DCE) involving 201 adults with AA in the US and Europe, efficacy data for ritlecitinib 50 mg once daily (QD) and placebo from the ALLEGRO phase 2b/3 trial (NCT03732807) of ritlecitinib efficacy and safety, and safety data from an integrated safety analysis of four studies in AA. The DCE included 6 treatment attributes: 3 benefits (chance of achieving ≥80% scalp hair coverage, moderate or normal eyebrows, and moderate or normal eyelashes) and 3 risks (3-year risks of serious infections, blood clots, and cancer). Choice probabilities were calculated using the estimated utility function. Weighted net benefit scores were calculated using MCDA. Stochastic multicriteria acceptability analysis (SMAA) assessed the impact of uncertainty and preference heterogeneity on net benefit conclusions.

Results: Ritlecitinib 50 mg had a higher weighted net benefit score than placebo with a predicted choice probability of 70.9% (95% CI, 61.2%-77.5%), indicating that on average patients would likely evaluate benefits to outweigh risks. The probability of positive weighted net benefit based on the SMAA was 78%.

Conclusions: Ritlecitinib 50 mg QD demonstrated a positive benefit-risk profile compared with placebo in adult patients with AA.