Using Patient Preference to Inform Ritlecitinib Dose Selection for Alopecia Areata Treatment

OBJECTIVES: To evaluate benefit-risk profiles of two doses of ritlecitinib (50 mg vs. 30 mg daily) integrating patient preferences and clinical efficacy estimates for ritlecitinib, an investigational treatment for alopecia areata (AA).

METHODS: A discrete-choice experiment (DCE) elicited preferences for benefit and safety attributes of systemic AA treatments. Benefits included probabilities of ≥80% scalp hair coverage and achieving moderate to normal eyebrows and eyelashes. Risks included 3-year probabilities of serious infection (SI), cancer, and blood clots. Preference estimates were used to calculate the maximum acceptable risk (MAR) that patients would accept for expected increases in benefit from choosing a higher dose of ritlecitinib over a lower dose. Ritlecitinib benefits were calculated from the ALLEGRO-2b/3 clinical trial. MARs were calculated separately for each risk and jointly for all possible combinations.

RESULTS: Adults (n=201) in the United States (n=62) and Europe (United Kingdom [n=22], France [n=3], Germany [n=30], Spain [n=25], Italy [n=59]) with physician confirmation of ≥50% scalp hair loss from AA participated. To achieve the expected increases in the probabilities of ≥80% scalp hair coverage and moderate to normal eyebrows and eyelashes when choosing 50 mg over 30 mg ritlecitinib, ...patients would be willing to accept increases in each 3-year risk (mean (95% CI)) up to 3.88 absolute percentage-points (2.86; 4.90) for SI, 1.63 (1.08; 2.18) for cancer, and 5.30 (3.60; 7.00) for a blood clot.

CONCLUSIONS: Patients with AA value increases in the probabilities of hair regrowth on the scalp, eyebrows and eyelashes, with the average patient accepting increases in potential treatment-related risks for a higher dose with higher efficacy. The DCE approach to measuring risk tolerance, combined with comparisons to expected or acceptable benefit and risk differences, can be used to inform optimal dose selection for an AA treatment.