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BackgroundThe 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).ObjectiveThe objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.MethodsTwo 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.ResultsIn 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.ConclusionsRitlecitinib 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 registriesClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).

Introduction/Background The oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and safety in patients aged ≥12 years with alopecia areata (AA) with ≥50% hair loss in the ALLEGRO phase 2b/3 study. ALLEGRO-LT is an ongoing phase 3 open-label study investigating the long-term safety and efficacy of ritlecitinib in patients aged ≥12 years with AA with ≥25% hair loss. Objectives This post hoc analysis of ALLEGRO-LT evaluated the efficacy of ritlecitinib through Month 15 in patients with AA by the extent of scalp hair loss at baseline. Methods The open-label, multicenter, long-term ALLEGRO-LT study (NCT04006457) enrolled patients into two arms: (1) roll-over patients who had received study intervention in either the ALLEGRO phase 2a study (NCT02974868) or phase 2b/3 study (NCT03732807), and (2) de novo patients who were aged ≥12 years with AA with ≥25% scalp hair loss at baseline and had not participated in either study. This post hoc analysis only included patients in the de novo cohort. All patients received an initial 4-week loading dose of ritlecitinib 200 mg once-daily (QD) followed by ritlecitinib 50 mg QD. Outcomes included median Severity of Alopecia Tool (SALT) score over time and the proportions of patients with SALT score ≤20 (≤20% scalp hair loss) and ≤10 at Month 15. Patients were stratified by extent of scalp hair loss at baseline (measured by SALT score) as follows: 25 to <50, 50 to <75, 75 to <90, 90 to <95, and 95 to 100. Analyses were based on observed data. Results 1052 patients were enrolled in ALLEGRO-LT, of whom 447 patients received ritlecitinib in the de novo arm. Of the 447 de novo patients, 26.6% (n=119), 16.8% (n=75), 9.2% (n=41), 2.9% (n=13), and 44.5% (n=199) had baseline SALT scores 25 to <50, 50 to <75, 75 to <90, 90 to <95, and 95 to 100, respectively. Patients with baseline SALT score ≥95 generally had longer mean duration of AA episode (3.47 years) and disease duration (10.86 years) than patients with SALT score <50 at baseline (2.53 and 8.79 years, respectively). A greater proportion of patients with baseline SALT score <50 had active shedding at baseline (49.6%) vs patients with baseline SALT score ≥95 (11.6%). Across all groups, median SALT scores improved (decreased) from baseline through Month 15. At Month 15, median SALT scores were 1.0, 1.2, 1.4, 2.4, and 30.9 for the 25 to <50, 50 to <75, 75 to <90, 90 to <95, and 95 to 100 groups, respectively. At Month 15, 93.0% (93/100), 87.7% (57/65), 88.2% (30/34), 83.3% (10/12), and 43.9% (68/155) of patients, respectively, achieved SALT scores ≤20, and 81.0% (81/100), 76.9% (50/65), 73.5% (25/34), 75.0% (9/12), and 33.5% (52/155) of patients, respectively, achieved SALT score ≤10. Conclusions After 15 months of ritlecitinib treatment, patients with less than 95% hair loss at baseline reached median SALT scores of <2.4, reflecting almost complete scalp hair regrowth. More refractory disease was seen in the subset of patients with extensive (≥95%) hair loss at baseline; however, over one third of these patients achieved clinically meaningful SALT response (SALT ≤20 and SALT ≤10) at Month 15. Overall, ritlecitinib was efficacious in patients with AA with ≥25% hair loss including those with extensive hair loss at baseline. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata (AA) is an immune-mediated form of hair loss that can occur at any age, often with a significant mental health burden., Objectives: We aimed to provide estimates of the lifetime incidence of AA, and the impacts on mental health, healthcare utilisation and work-related outcomes, assessing variation across major sociodemographic subgroups., Methods: AA cases were identified in primary care from the UK population-based Oxford-Royal College of General Practitioners Research and Surveillance Centre database (2009-2018). Lifetime incidence of AA was estimated at age 80 using modified time-to-event models with age as the timescale, overall and stratified by sex, ethnicity, deprivation, and geography. Mental health, healthcare utilisation and work-related outcomes were assessed in the two years after AA diagnosis compared to matched unaffected controls, and stratified by the same sociodemographic subgroups ., Results: 6,961 people developed AA during the study period. Overall lifetime incidence of AA was 2.11% (95% Confidence Interval [CI] 2.06, 2.16%). Females had a higher lifetime incidence 2.35% (95%CI 2.28, 2.43%) than males 1.88% (95%CI 1.81, 1.94%). Lifetime incidence was higher in those of Asian ethnicity 5.87% (95%CI 5.51, 6.24), other 4.47% (95%CI 3.63, 5.31), mixed 4.44% (95%CI 3.50, 5.37) and black 3.03% (95%CI 2.63, 3.42) ethnicity, compared to white ethnicity 1.74% (95%CI 1.68, 1.80). Lifetime incidence was highest in those with the greatest deprivation; most-deprived quintile 2.92% (95%CI 2.77, 3.07%) compared to least-deprived 1.68% (95%CI 1.59, 1.78%). Across sociodemographic subgroups, people with AA of black ethnicity were most likely to have anxiety (adjusted Odds Ratio versus matched controls 2.92, 95%CI 1.71, 4.91), and had the greatest risk of time off work (adjusted Hazard Ratio versus matched controls 2.54, 95%CI 1.80, 3.56)., Conclusions: AA affects around 1 in 50 people over their lifetime. Incidence and the impact of AA on mental health and work outcomes, is highest in ethnic groups other than white. Clinicians should be aware of the marked heterogeneity in the incidence and impact of AA, and support targeted healthcare to groups at the highest risk of alopecia and its consequences.The study protocol for this retrospective observational study was registered with ClinicalTrials.gov (Identifier: NCT05727306)., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)