Ritlecitinib Demonstrates Effectiveness in Subgroup Analysis of Asian Patients

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While the global prevalence of alopecia areata (AA) is approximately 2%, data on its occurrence in Asian populations remain limited.¹ Studies from China and Japan suggest a prevalence of AA ranging from 0.24% to 2.5%, with some studies indicating a higher incidence in individuals of Asian descent compared to other racial groups. However, the precise factors influencing these regional variations in prevalence remain unclear.²

In the treatment of AA, systemic therapies have been limited by efficacy and safety concerns. Historically, therapies such as corticosteroids (topical, intralesional, or systemic) and contact immunotherapy have been used, but these treatments often show variable clinical responses and can lead to significant adverse effects, including decreased bone density, infections, and changes in blood pressure.³ More recently, Janus kinase (JAK) inhibitors, such as baricitinib and ritlecitinib, have shown promising results for the treatment of severe AA. Baricitinib, a JAK1/2 inhibitor, was approved in multiple countries for the treatment of adult patients with severe AA.⁴ Ritlecitinib, a highly selective JAK3 inhibitor, has also demonstrated efficacy in clinical trials, with its mechanism of action involving inhibition of key inflammatory cytokines like IL-2, IL-4, IL-7, IL-15, and IL-21, which are central to the pathogenesis of AA.⁵

Ritlecitinib’s impact on immune responses has been particularly relevant in the context of AA treatment. By inhibiting the signaling pathways that lead to the activation of autoreactive CD8+ T-cells and NK cells, ritlecitinib helps to reduce inflammation and immune cell infiltration in the hair follicle, leading to hair regrowth. This has been confirmed in several clinical studies, including the ALLEGRO phase 2b/3 trial (NCT03732807), which assessed the efficacy and safety of ritlecitinib in a diverse patient population.⁶

Subgroup Analysis of Asian Patients

This subgroup analysis of the ALLEGRO study specifically evaluated the efficacy and safety of ritlecitinib in Asian patients, who made up 25.9% of the study population.⁷ The study enrolled patients aged 12 and older with a diagnosis of AA and ≥50% scalp hair loss. Patients were randomized to receive either ritlecitinib (30 mg, 50 mg, or 200/50 mg) or a placebo for 24 weeks, followed by a 24-week extension period. The primary endpoint of the study was achieving a Severity of Alopecia Tool (SALT) score of ≤20, indicating that no more than 20% of the scalp had hair loss.

The results showed that ritlecitinib was effective in the Asian subgroup, with a higher proportion of patients in the 30 mg and 50 mg ritlecitinib groups achieving a SALT score ≤20 and ≤10 compared to placebo at both 24 and 48 weeks. Specifically, at week 24, 36.4% and 35.7% of patients in the 200/50 mg and 200/30 mg groups, respectively, achieved a SALT score ≤20, compared to only 3.2% in the placebo group. Furthermore, 27.3% and 21.4% of patients in the 200/50 mg and 200/30 mg groups, respectively, achieved a more stringent SALT score ≤10 at week 24. These findings were consistent with the results observed in the overall study population.

In addition to the clinician-reported outcomes, patient-reported outcomes were also measured using the Patient Global Impression of Change (PGI-C) scale. A higher proportion of patients in the ritlecitinib treatment groups reported being "moderately improved" or "greatly improved" at both week 24 and week 48, compared to the placebo group.

Safety Profile

Regarding safety, the incidence of adverse events (AEs) was similar between the Asian subgroup and the overall study population. The most common AEs reported included nasopharyngitis, folliculitis, and upper respiratory tract infections, most of which were mild to moderate in severity. Serious AEs (SAEs) were rare, with no deaths reported. Of the 186 Asian patients included in the analysis, 64.7% to 85.7% of those in the ritlecitinib treatment groups reported AEs during the placebo-controlled period. The incidence of SAEs was low and not dose-dependent. The most notable adverse events included transient decreases in lymphocyte and neutrophil counts, and a small number of cases of herpes zoster and herpes simplex infections, which resolved without discontinuation of treatment.

Conclusion

The results of this subgroup analysis provide robust evidence for the efficacy and safety of ritlecitinib in Asian patients with severe AA. The positive outcomes observed in the Asian subgroup mirror those seen in the overall study population, highlighting the potential of ritlecitinib as an effective treatment option for severe AA across different ethnic groups. With its favorable safety profile and demonstrated efficacy, ritlecitinib may become an important part of the therapeutic arsenal for patients with AA, particularly those in need of a long-term, systemic treatment option. However, further research is needed to explore the long-term effects of ritlecitinib and its role in treating AA in different populations, including other ethnic groups.

References

1. Lee MH, Bae KS. Implementation of Miettinen-Nurminen score method with or without stratification in R. Transl Clin Pharmacol. 2022;30(3):155-162. doi:10.12793/tcp.2022.30.e16
2. Furue M, Yamazaki S, Jimbow K, et al. Prevalence of dermatological disorders in Japan: a nationwide, cross-sectional, seasonal, multicenter, hospital-based study. J Dermatol. 2011;38(4):310-320. doi:10.1111/j.1346-8138.2011.01209.x
3. Fukuyama M, Ito T, Ohyama M. Alopecia areata: Current understanding of the pathophysiology and update on therapeutic approaches, featuring the Japanese Dermatological Association guidelines. J Dermatol. 2022;49(1):19-36. doi:10.1111/1346-8138.16207
4. King B, Ohyama M, Kwon O, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. doi:10.1056/NEJMoa2110343
5. Thorarensen A, Dowty ME, Banker ME, et al. Design of a janus kinase 3 (JAK3) specific inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) allowing for the interrogation of JAK3 signaling in humans. J Med Chem. 2017;60(5):1971-1993. doi:10.1021/acs.jmedchem.6b01694
6. Hordinsky M, Hebert AA, Gooderham M, et al. Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial. Pediatr Dermatol. 2023;40(6):1003-1009. doi:10.1111/pde.15378
7. Zhang X, Ye Y, Sun W, et al. Efficacy and safety of ritlecitinib in Asian patients with alopecia areata: A subgroup analysis of the ALLEGRO phase 2b/3 trial. J Dermatol. Published online March 12, 2025. doi:10.1111/1346-8138.17539