Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program.
Am J Clin Dermatol
; 25(2): 299-314, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38263353
ABSTRACT
BACKGROUND:
The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA).OBJECTIVE:
The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.METHODS:
Two cohorts were analyzed a placebo-controlled and an all-exposure cohort. Proportions and study size-adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported.RESULTS:
In the placebo-controlled cohort (n = 881; median exposure 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2-75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events.CONCLUSIONS:
Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available). TRIAL REGISTRIES ClinicalTrials.gov NCT02974868 (date of registration 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tryptamines
/
Alopecia Areata
/
Antineoplastic Agents
Type of study:
Clinical_trials
Limits:
Humans
Language:
En
Journal:
Am J Clin Dermatol
Journal subject:
DERMATOLOGIA
Year:
2024
Document type:
Article
Affiliation country: