Ritlecitinib Spurs Hair Regrowth in Alopecia Areata

The kinase inhibitor ritlecitinib (Litfulo; Pfizer) could provide fresh hope for people living with alopecia areata, a recent study found. Researchers of the new study have discovered that the drug reshapes immune responses in the scalp while encouraging the biological machinery needed for hair growth.¹ 

The research highlights 2 important takeaways for patients and clinicians: earlier treatment may offer the best chance of success, and biomarker-driven care could help usher in a new era of precision medicine in alopecia areata. The findings, published in the journal Allergy, suggest that treatment could eventually be tailored to individual patients based on molecular “fingerprints.”

One of the most promising findings from the study was the identification of potential biomarkers in alopecia areata. | Image Credit: onephoto - stock.adobe.com

Alopecia areata (AA), an autoimmune condition that causes sudden and sometimes severe hair loss, affects millions worldwide.² It can appear as small bald patches (patchy AA) or progress to more severe forms, such as alopecia totalis, which involves complete scalp hair loss, and alopecia universalis, which leads to loss of all body hair.¹

For many patients, the condition is unpredictable, with sudden relapses and significant emotional and social burdens. While treatments have improved in recent years, doctors have long struggled to predict who will respond, and how quickly.

Ritlecitinib, a JAK3/TEC kinase inhibitor, is one of the first drugs specifically approved for severe AA, including in adolescents. But exactly how it works at the molecular level—and why some patients respond better than others—has remained unclear.

The new analysis comes from the ALLEGRO-2a clinical trial, which tested ritlecitinib in patients with at least 50% scalp hair loss. A subset of participants agreed to provide scalp biopsies and blood samples, giving researchers a window into what was happening inside hair follicles during treatment.

“Following treatment with ritlecitinib, CFB in type I and II immunity and hair growth gene expression levels in lesional scalp at week 12 correlated significantly with disease improvement (scalp hair regrowth) at week 24, suggesting that early molecular response is linked to clinical response,” described the researchers.

Over 12 to 24 weeks, the researchers saw a 2-part transformation in the scalp, one of which was suppressed immune activity. Genes linked to the autoimmune attack on hair follicles, including those driving type I and type II inflammatory pathways, were dialed down. The group also observed reactivated hair growth genes. Genes responsible for producing keratin, the structural protein in hair, switched back on, restoring the biological foundation for regrowth.

These changes were most pronounced in patients with patchy AA. Those with more extensive forms, alopecia totalis and universalis, also improved but generally at a slower pace.

One of the most promising findings from the study was the identification of potential biomarkers—molecular signals that could predict or track treatment success. Patients who at the start of the trial had higher expression of hair keratin genes and lower expression of inflammatory genes were more likely to see regrowth.

“Upon treatment with ritlecitinib, the significant correlation between changes in expression levels of JAK3, ITK, and BTK (ritlecitinib mechanistic targets) and disease improvement indicates that effective targeting and modulation of these genes are important for response to ritlecitinib treatment,” noted the researchers.

In addition, blood tests revealed protein markers that shifted early in treatment and mirrored improvements in scalp hair. If validated, these serum markers could allow doctors to monitor progress with a simple blood draw instead of repeated biopsies.

Despite the encouraging findings, the study had limitations, including having a relatively small group of patients who were followed for just 24 weeks. Patients with the most severe forms of AA often need longer therapy to see meaningful regrowth, meaning the results may underestimate the drug’s full potential.

Future studies will need to validate the candidate biomarkers in larger populations and track changes over longer periods. Researchers also plan to use more advanced technologies, such as RNA sequencing and spatial transcriptomics, to deepen understanding of how immune cells interact with hair follicles during treatment.

"In conclusion, these results provide support that treatment with ritlecitinib improves the gene expression profile in lesional scalp in patients with AA and is correlated with hair regrowth response," the authors wrote. "Future studies are needed to assess changes beyond 24 weeks. From a scientific and translational perspective, this study provides a data-driven framework for identifying molecular biomarkers with predictive potential for targeted therapies in AA subtypes."

References

1. Xi L, Peeva E, Yamaguchi Y, et al. Multiomics analysis of the response to ritlecitinib in alopecia areata subtypes and correlation with efficacy. Allergy. 2025;80(8):2348-2360. doi:10.1111/all.16659
2. Alopecia areata. National Alopecia Areata Foundation. Accessed August 28, 2025. https://www.naaf.org/alopecia-areata