Ritlecitinib Shows Significant Reduction in Alopecia Areata Psychosocial Burden

While ritlecitinib (Litfulo; Pfizer) has demonstrated significant efficacy in achieving hair regrowth for patients with severe alopecia areata, new long-term data from the ALLEGRO-2b/3 trial (NCT03732807) show that its therapeutic benefit extends to significantly reducing the substantial psychosocial burden associated with the disease.

The post hoc analysis, published in the International Journal of Dermatology, suggests patients may experience improvements in psychosocial burden after hair regrowth.

Alopecia areata is a complex autoimmune disease affecting hair follicles, which causes nonscarring hair loss in approximately 2% of the global population. The condition's high visibility and chronic relapsing nature can have substantial effects on quality of life (QOL), leading to significant impacts on emotional well-being and daily activities.²

Ritlecitinib, a dual inhibitor of Janus kinase (JAK) 3 and the TEC family kinases, was approved by the FDA in 2023 for severe alopecia areata in adults and adolescents aged 12 and older.¹ Although the initial 24-week placebo-controlled phase of ALLEGRO-2b/3 showed significant hair regrowth as measured by the Severity of Alopecia Tool, it did not show a corresponding improvement in patient-reported emotional symptoms or activity limitations as measured by the Alopecia Areata Patient Priority Outcomes (AAPPO) questionnaire. This outcome suggested a potential time lag between clinical and patient-reported improvements.

“Since hair regrowth can precede patient-reported outcome (PRO) improvement, individuals with a clinical response at week 24 may need additional follow-up time to capture any delayed PRO effects,” the authors explained.

The additional ALLEGRO-2b/3 analysis examined 48-week data, comparing outcomes between 325 participants receiving the therapeutic 50-mg once-daily (QD) maintenance dose of ritlecitinib (with or without a 200-mg, 4-week loading dose) to those on a subtherapeutic 10-mg dose, which served as a conservative proxy for placebo for the long-term evaluation.

The analysis focused on changes from baseline in AAPPO emotional symptoms and activity limitation domain scores. By week 48, the least squares mean (LSM) changes from baseline in both emotional symptoms and activity limitation domain scores had generally improved for all 50-mg groups, while the 10-mg group's scores showed a general plateau or slight worsening.

The analysis suggests that significant improvements in psychosocial burden require extended treatment time. Statistically significant differences in improvement between the 50-mg groups and the 10-mg group were first observed starting at week 34 for emotional symptoms and week 40 for activity limitations.

At the final evaluation point of week 48, the combined 50-mg group showed a statistically significant improvement compared with the 10-mg group for both emotional symptoms (LSM difference, –0.41; 95% CI, −0.63 to −0.18; P = .0004) and activity limitations (LSM difference, –0.17; 95% CI, −0.34 to −0.00; P = .0469).

Item-level analyses further highlighted areas where ritlecitinib treatment benefitted patients, with the largest improvements vs the subtherapeutic dose seen for items related to self-consciousness, embarrassment (emotional symptoms domain), and interactions with others (activity limitations domain).

The study was limited by the inclusion criteria for ALLEGRO-2b/3, including the exclusion of patients with less than 50% scalp hair loss and those whose alopecia areata episode was longer than 10 years at baseline, the authors noted. Sample sizes were also limited. Still, the findings complement the primary ALLEGRO-2b/3 analysis, they noted.

“By week 48, ALLEGRO-2b/3 participants reported greater improvements in [emotional symptoms] and [activity limitations] due to hair loss with the 50-mg ritlecitinib QD maintenance dose (+/− 200-mg 4-week loading dose) than with the subtherapeutic 10-mg QD ritlecitinib dose,” the authors concluded. “Overall, these findings show item-level AAPPO differences and may demonstrate improvements in psychosocial burden following hair regrowth with ritlecitinib.”

References

1. Law EH, Sherif B, Mostaghimi A, 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. Int J Dermatol. Published online October 9, 2025. doi:10.1111/ijd.70035

2. Muntyanu A, Gabrielli S, Donovan J, et al. The burden of alopecia areata: A scoping review focusing on quality of life, mental health and work productivity. J Eur Acad Dermatol Venereol. 2023;37(8):1490-1520. doi:10.1111/jdv.18926