ALLEGRO-2b/3: Post-Hoc Analysis Suggests Alopecia Areata Improves with Ritlecitinib

Adults with alopecia areata experienced meaningful improvements in emotional well-being and daily functioning after 48 weeks of ritlecitinib 50 mg use, according to recent long-term data.1

These findings were the result of the ALLEGRO-2b/3 analysis (NCT03732807), the results of which had previously shown that ritlecitinib treatment led to notable hair regrowth and other patient-reported improvements versus placebo.2 During the 24-week placebo-controlled trial phase, improvements in AA Patient Priority Outcomes (AAPPO) emotional symptoms (ES) or activity limitations (AL) were not noted.

In this analysis, authored by investigators such as Ernest H. Law, PharmD, PhD, from Pfizer, Inc., the investigators looked at AAPPO scores in patients from the aforementioned study given a 50-mg ritlecitinib maintenance dose (+/− 4-week loading dose of 200 mg) and those given subtherapeutic ritlecitinib 10 mg through the 48-week mark.

“This post hoc analysis of ALLEGRO-2b/3 data compares improvements in AAPPO ES and AL domain and item scores between the ritlecitinib 50-mg QD maintenance dose…and the subtherapeutic ritlecitinib 10-mg QD dose through Week 48,” Law and colleagues wrote.1

ALLEGRO-2b/3 Post-Hoc Analysis

The investigative team highlighted that within the ALLEGRO-2b/3 studies, a total of 718 eligible study participants were randomized to be treated with either a placebo or 1 of a possible 5 dosing regimens of ritlecitinib. This 48-week study was double-blinded consisted of an initial 24-week placebo-controlled period. This period was later followed by a 24-week extension, during which those taking part who were previously given a placebo transitioned to active ritlecitinib therapy.

In this exploratory analysis, an assessment of 3 ritlecitinib treatment cohorts was conducted. These arms were as follows: (a) study subjects given 50 mg once-per-day (QD) only; (b) subjects initiating with a 200 mg QD loading dose for a 4-week course followed by a 50 mg QD maintenance dose (200/50 mg); and (c) the pooled population of all study participants who were given any 50-mg dose, combining both a and b groups. The comparison group consisted of individuals who were given a subtherapeutic 10-mg QD dose.

The Alopecia Areata Patient Priority Outcomes (AAPPO) instrument, a validated 11-item self-administered questionnaire, was implemented by Law and coauthors to evaluate the effect of alopecia areata in individuals aged ≥12 years. Changes in least squares mean (LSM) from the point of baseline (CFBs) were calculated by the investigators for domain scores across the full analysis set as well as for those who showed baseline domain scores which were ≥1.

Law and colleagues looked at item-level shifts, analyzing them for participants with baseline item scores ≥2. This was carried out since lower baseline scores (on a 0–4 scale) would suggest less frequent or severe impacts related to hair-loss.

In this post-hoc analysis, 325 participants were included. There were 132 in the 200/50-mg cohort, 130 in the 50-mg cohort, and 63 in the 10-mg cohort. Across all of the 50-mg arms of this analysis, Law and coauthors found that LSM CFBs in the Emotional Symptoms (ES) and Activity Limitations (AL) domain scores generally improved through the 48-week mark. They noted statistically significant differences versus the 10-mg arm, observed starting at the 34-week mark for ES and the 40-week mark for AL.

Responder rates for individual ES and AL items were also shown by the investigators to tend to rise through the 48-week mark in all 50-mg groups. The team added that the greatest improvements relative to the 10-mg group were observed for ES items 5 and 6, which they added had evaluated self-consciousness and embarrassment, and AL item 11, which assesses interactions with others.

“The results of this study suggest that a longer follow-up period may be needed to observe downstream psychosocial improvement following effective treatment,” the investigative team concluded.1

References

1. EH Law, B Sherif, A Mostaghimi, et al. Improvement in Patient-Reported Emotional Symptoms and Activity Limitations due to Hair Loss in Patients With Alopecia Areata Treated With Ritlecitinib: Additional Analyses From ALLEGRO-2b/3. International Journal of Dermatology (2025): 1–9, https://doi.org/10.1111/ijd.70035.

2. B King, X Zhang, WG Harcha, et al. Efficacy and Safety of Ritlecitinib in Adults and Adolescents With Alopecia Areata: A Randomised, Double-Blind, Multicentre, Phase 2b-3 Trial. Lancet 401, no. 10387 (2023): 1518–1529, https://doi.org/10.1016/s0140-6736(23)00222-2.