Distribution of SALT Scores with Ritlecitinib Treatment up to 24 months from the ALLEGRO Phase 2b/3 and Long-Term Phase 3 Clinical Studies in Alopecia Areata

Abstract

Background:• Alopecia areata (AA) is an autoimmune disease that has an underlying immuno-inflammatorypathogenesis and is characterized by non-scarring hair loss ranging from small patches to completescalp, face, and/or body hair loss1• Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, demonstrated efficacy and safety up to 48 weeks inpatients aged ≥12 years with AA in the ALLEGRO phase 2b/3 study (NCT03732807; “ALLEGRO-2b/3”)2• The long-term efficacy of ritlecitinib in patients who rolled over from ALLEGRO-2b/3 to the ongoingphase 3, open-label ALLEGRO-LT study (NCT04006457) has been reported in terms of the proportions ofpatients with Severity of Alopecia Tool (SALT) scores of ≤20 and ≤10 (≤20% or ≤10% scalp without hair)at Month 243• However, the distribution of SALT scores in the overall population, including patients not reaching theSALT score ≤20 and ≤10 thresholds, has not yet been describedOBJECTIVE• This study describes changes in the distribution of SALT scores over 24 months of ritlecitinib treatmentin the overall population and in age and disease severity subgroups Methods: Study design and patients• Key inclusion criteria in ALLEGRO-2b/3:- Age ≥12 years- Diagnosis of AA with ≥50% scalp hair loss due to AA (including alopecia totalis [AT] and alopecia universalis [AU])- Maximum duration of current episode of hair loss ≤10 years• This analysis includes patients who received ritlecitinib 50 mg once daily (QD) without a loading dose inALLEGRO-2b/3 and who subsequently rolled over into ALLEGRO-LT where they continued to receiveritlecitinib 50 mg QD (Figure 1)- Continuation criteria for adolescents (aged 12-17 years) in ALLEGRO-LT: ≥50% improvement from baseline in SALT scoreby Month 3 for rollover patients from ALLEGRO-2b/3 and SALT score ≤20 by Month 6 in ALLEGRO-LTFigure 1. Study design and patient populationCombinedritlecitinib50 mg group(N=191)ALLEGRO phase 2b/3 ALLEGRO-LTLoading(4 weeks)Maintenance(20 weeks)Extension(24 weeks)Long-term study(60 months)Group A (n=131) 200 mg 50 mg 50 mg 50 mgGroup B (n=129) 200 mg 30 mg 30 mg 50 mgGroup C (n=130) 50 mg 50 mg 50 mg 50 mgGroup D (n=132) 30 mg 30 mg 30 mg 50 mgGroup E (n=61) 10 mg 10 mg 10 mg 50 mgGroup F (n=63) Placebo Placebo 200 mg 50 mg 50 mgGroup G* (n=61) Placebo Placebo 50 mg 50 mgDe novo group (n=447) 200 mg 50 mg*Data while on placebo were not included in this analysis; data from patients in Groub G were rebaselined from the start of treatment with ritlecitinib.Assessments and statistical analysis• The distribution of patients according to SALT score (as observed) was assessed through Month 24 forthe overall population and subgroups based on age (adults [≥18 years] vs adolescents [12-17 years]) anddisease severity (patients with AT/AU vs those without AT/AU)• The data cutoff date was December 9, 2022 Results: The analysis included 191 patients (27 adolescents and 164 adults) (Table 1)• At the time of data cutoff, 71 patients had discontinued; withdrawal bypatient (n=19), adverse events (n=18), and lack of efficacy (n=14) were themost common reasons for discontinuation• The distribution of participants by SALT score (as observed) at baseline, Month12, and Month 24 are presented for the overall population (Figure 2)(Interactive dynamic plot)• Per the inclusion criteria, all participants had a SALT score of ≥50 at baseline;136/191 patients (71.2%) had SALT >90• Among patients who had a nonmissing SALT score, 56/178 (31.5%), 37/164(22.6%), and 17/120 (14.2%) were in the SALT >90-100 category at Months 6,12, and 24, respectively• Reductions in the number of patients in the other SALT >50 categories wereobserved from baseline through Month 24• At Month 12, 56/164 (34.2%) and 18/164 (11.0%) patients were in the SALT0-10 and >10-20 categories, respectively, with 61/120 (50.8%) and 12/120(10.0%) patients in these categories at Month 24• Among the patients with AT/AU at baseline, 18/69 (26.1%) and 6/69 (8.7%)were in the SALT 0-10 and >10-20 categories, respectively, at Month 12; 25/47(53.2%) and 3/47 (6.4%) were in these categories, respectively, at Month 24(Figure 3) (Interactive dynamic plot)• For the adolescent participants, 10/22 (45.5%) and 4/22 (18.2%) were in theSALT 0-10 and >10-20 categories, respectively, at Month 12, and 11/14(78.6%) and 0/14 (0%) were in these categories at Month 24 (Figure 4) Conclusions:• Over 24 months, daily treatment with ritlecitinib 50 mg resulted in fewer patients inthe highest SALT score categories• These data provide a comprehensive overview of patient response to ritlecitinibtreatment and enable us to understand treatment response and time frames whileon treatment with ritlecitinib • This information can empower clinicians when counseling patients and managingtreatment expectations based on patient characteristics• This study also shows that response to treatment improves over time, whichsuggests that adequate time should be given when assessing treatment efficacy