Updated Integrated Safety Analysis of Ritlecitinib up to ~ 5 Years in Patients with Alopecia Areata from the ALLEGRO Clinical Trial Program.

BACKGROUND

Ritlecitinib, an oral Janus kinase (JAK) 3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor, demonstrated safety in patients aged 12 years and older with alopecia areata (AA) in an initial integrated analysis of 4 clinical studies for up to 2 years.

OBJECTIVE

This updated integrated safety analysis evaluated the safety of ritlecitinib up to ~ 5 years in patients aged ≥ 12 years with AA from the ALLEGRO clinical trial program.

METHODS

Safety data were pooled from 4 studies. Two groups were analyzed: patients who received any dose of ritlecitinib (30 mg or 50 mg with or without a 4-week 200 mg loading dose, or 10 mg daily) ("any-ritlecitinib" group) and a subset of the any-ritlecitinib group including only patients who received ritlecitinib 50 mg daily with or without a 4-week 200 mg daily loading dose (ritlecitinib 50 mg ± 200-mg group). Safety data were summarized descriptively. Proportions and incidence rates (IRs; IR/100 patient-years [PYs]) of adverse events (AEs) were evaluated.

RESULTS

In the ritlecitinib 50-mg ± 200-mg (N = 1228) and any-ritlecitinib (N = 1294) groups, median duration of exposure was 1197 days (3261.5 PYs) and 1204 days (3539.5 PYs), respectively. AEs occurred in 1070 patients (87.1%; 148.1/100 PYs) in the 50-mg ± 200-mg group and 1158 patients (89.5%; 167.9/100 PYs) in the any-ritlecitinib group. The most common AEs included headache, positive SARS-CoV-2 test, and nasopharyngitis. Serious AEs were reported in 6.8% of patients (2.6/100 PYs) in the 50-mg ± 200-mg group and 6.8% of patients (2.5/100 PYs) in the any-ritlecitinib group. There were two deaths. Overall, 8.1% of patients (3.0/100 PYs) and 8.4% of patients (3.0/100 PYs) in the 50-mg ± 200-mg and any-ritlecitinib groups, respectively, had an AE that led to discontinuation from the study or study drug. IRs for both groups were 0.1/100 PYs for opportunistic infections, 1.0/100 PYs for herpes zoster, 0.3/100 PYs for malignancies (excluding nonmelanoma skin cancer), and 0.2/100 PYs for major adverse cardiovascular events.

CONCLUSIONS

In this updated integrated safety analysis of the ALLEGRO clinical trials, long-term ritlecitinib treatment was generally well tolerated up to ~ 5 years in patients aged ≥ 12 years with AA. The overall safety profile was consistent with previously reported data.

CLINICAL TRIAL REGISTRATION: NCT03732807, NCT04006457, NCT04517864, NCT02974868. Video Abstract Updated integrated safety analysis of ritlecitinib up to ~ 5 years in patients with alopecia areata from the ALLEGRO clinical trial program (MP4 407314 KB).