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. Graphical Abstract Video Abstract <MediaObject ID="MOESM2"> <Caption Language="En" xml:lang="en"> <CaptionContent> Video Abstract </CaptionContent> </Caption> <VideoObject FileRef="MediaObjects/40257_2026_1062_MOESM2_ESM.mp4" VideoID="9LcKSvCnaMjo7-D4c9r4z_"> <Caption Language="En" xml:lang="en"> <CaptionContent> Updated integrated safety analysis of ritlecitinib up to ~ 5 years in patients with alopecia areata from the ALLEGRO clinical trial program (MP4 407314 KB) </CaptionContent> </Caption> </VideoObject> </MediaObject>

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

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2026年7月22日

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Maryanne Senna,
Sameh Hanna,
Rie Ueki,
Xingqi Zhang,
Crystal Aguh,
Bianca Maria Piraccini,
Dalia Wajsbrot,
Edward Nagy,
Mojgan Sadrarhami,
Simon Chen,
Robert Wolk,
Helen Tran,
Alexandre Lejeune

摘要

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.

Graphical Abstract

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)