Long-Term Efficacy and Safety of Ritlecitinib in Adults and Adolescents with Alopecia Areata: 3-Year Results from the ALLEGRO Phase 2b/3 and ALLEGRO-LT Phase 3 Clinical Studies

BACKGROUND/OBJECTIVE: Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, demonstrated efficacy over 48 weeks in patients aged ≥ 12 years with alopecia areata (AA) in the ALLEGRO phase 2b/3 study and initial extension up to month 24 in the ALLEGRO-LT study. We aimed to evaluate the efficacy of ritlecitinib up to 3 years in patients with AA from the ALLEGRO phase 2b/3 and ongoing phase 3, open-label ALLEGRO-LT studies. METHODS: Patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss who received daily ritlecitinib 50 mg in ALLEGRO-2b/3 and rolled over to ALLEGRO-LT (continued 50 mg) were included. Observed and last observation carried forward (LOCF) data are reported based on the data cutoff (25 June 2024). Variables associated with treatment response were assessed using multivariable logistic regression. RESULTS: A total of 191 patients were included. At 3 years, 65.1% (observed) and 47.1% (LOCF) of patients had Severity of Alopecia Tool (SALT) score ≤ 20. Among patients with SALT score ≤ 20 at 1 year, most (88.3-89.6%) maintained this response at 3 years. SALT score ≤ 10 response rates at 3 years were 52.3% (observed) and 36.7% (LOCF). At 3 years, 31.2% (observed) and 22.5% (LOCF) of patients achieved SALT score 0 (complete scalp hair regrowth). Patients' Global Impression of Change response ("moderately" or "greatly" improved) rates at 3 years were 68.4% (observed) and 55.6% (LOCF). Female sex, White race, and less extensive and shorter duration of hair loss at baseline were associated with treatment response. The safety profile was consistent with the known safety profile of ritlecitinib. CONCLUSIONS: Ritlecitinib 50 mg demonstrated clinically meaningful clinician- and patient-reported efficacy up to 3 years, with no new safety signals observed. These data support the long-term use of ritlecitinib in patients aged ≥ 12 years with severe AA. [Graphical abstract and video abstract available online.]. CLINICAL TRIAL REGISTRATION: NCT03732807, NCT04006457, NCT04517864, NCT02974868.