Using patient preference to inform ritlecitinib dose selection for alopecia areata treatment

Ritlecitinib is an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma (JAK3/TEC) family kinase inhibitor approved for the treatment of severe alopecia areata (AA). Benefit-risk profiles of two doses of ritlecitinib (50 mg vs 30 mg once daily) were evaluated by integrating patient preferences and clinical efficacy and safety estimates for ritlecitinib. A discrete-choice experiment (DCE) was utilized to elicit 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. Potential risks included 3-year probabilities of serious infection, 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 ritlecitinib dose 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. Adults (n = 201) with physician-confirmed ≥50% scalp hair loss from AA participated. To achieve expected increases in the probabilities of ≥80% scalp hair coverage or moderate to normal eyebrows and eyelashes when choosing 50 mg over 30 mg of ritlecitinib, patients would be willing to accept increases in each 3-year risk up to a mean of 3.88 absolute percentage points (95% confidence interval [CI], 2.86-4.90) for serious infection, 1.63 (95% CI, 1.08-2.18) for cancer, and 5.30 (95% CI, 3.60-7.00) for blood clots. These results, combined with the estimated differences in risks between the two doses, indicate that patients with AA value increases in the probabilities of scalp, eyebrow, and eyelash hair regrowth, with the average patient accepting increases in potential treatment-related risks for the 50-mg dose in exchange for higher efficacy than 30 mg. The DCE approach to measuring risk tolerance, combined with comparisons to expected benefit and risk differences, can be used to optimize AA treatment dose selection.