OBJECTIVES: Ritlecitinib is an oral JAK3/TEC inhibitor with demonstrated clinical efficacy in hair regrowth in patients with alopecia areata (AA). JAK inhibition can be associated with potential risks of serious infections, malignancies, and blood clots. In the broader context of the risk profile for the JAK class, we aimed to understand whether ritlecitinib 50 mg once daily (QD) has a positive benefit-risk profile from the perspective of adult patients with AA.

METHODS: A patient-centered benefit-risk assessment combined preference data from a discrete choice experiment (DCE) involving n=201 patients across the United States and Europe, and efficacy data of ritlecitinib 50 mg daily dose and placebo from a phase 2b/3 dose-ranging and pivotal clinical trial. DCE data was used to elicit patient preferences for three key benefits (chance of achieving ≥80% scalp hair regrowth, and moderate or normal eyebrow and eyelash hair) and three risks (3-year risks of serious infections, blood clots, and cancer). Quantitative benefit-risk analyses determined the net benefit-risk (NBR) scores for ritlecitinib 50 mg daily and placebo, their predicted choice probabilities, including the sensitivity of the scores to uncertainty surrounding the clinical effect estimates and preference heterogeneity.

RESULTS: Ritlecitinib 50 mg daily achieved a higher net benefit-risk score (0.587) than placebo (0.465) and was expected to be preferred over placebo by patients with AA (predicted choice probability=65.9% (95% CI: [59.4; 71.5]). In sensitivity analyses, ritlecitinib had higher NBR scores than placebo, with 99.8% probability when accounting for uncertainty in the clinical effect estimates, 95.7% when accounting for preference heterogeneity, and 90.9% when accounting for both.

CONCLUSIONS: A dose of ritlecitinib 50 mg daily demonstrated a positive benefit-risk profile compared to placebo from the perspective of adult patients with AA. These findings may help to inform regulatory agencies, payers, clinicians, and patients considering ritlecitinib, for the treatment of AA.