New Hope for Hair Loss? Tyrosine Kinase Inhibitors Show Promise

clinical-trial PMID: 34863853

Quick Summary: Researchers are exploring new ways to treat alopecia areata (AA), a type of hair loss. This study found that two drugs, ritlecitinib and brepocitinib, helped improve hair loss biomarkers, potentially leading to hair regrowth.

What The Research Found

This study looked at how two drugs, ritlecitinib and brepocitinib, affect the scalp of people with alopecia areata. Both drugs showed positive changes in the scalp, suggesting they could help with hair regrowth. Ritlecitinib and brepocitinib work by targeting specific enzymes called tyrosine kinases, which are involved in inflammation.

Study Details

Who was studied: 46 people with alopecia areata.

How long: The study lasted 24 weeks (about 6 months).

What they took: Some participants received ritlecitinib, some brepocitinib, and some a placebo (a dummy pill).

What This Means For You

Potential for new treatments: These findings suggest that ritlecitinib and brepocitinib could be effective treatments for alopecia areata.

More research needed: This is just one study, and more research is needed to confirm these results and understand the long-term effects.

Not a quick fix: These are not over-the-counter supplements. They are investigational drugs that are not yet available to the public.

Study Limitations

Small study: The study only included a small number of people, so the results may not apply to everyone.

Short-term: The study only lasted 6 months, so we don't know how long the effects will last.

Focus on biomarkers: The study primarily looked at changes in the scalp, not just hair growth.

Not about Tyrosine supplements: This study is about drugs that target tyrosine kinases, not the amino acid tyrosine. Taking tyrosine supplements will not have the same effect.

Key Findings

This 24-week biopsy substudy found that ritlecitinib (JAK3/TEC inhibitor) and brepocitinib (TYK2/JAK1 inhibitor) significantly improved scalp alopecia areata (AA) biomarkers compared to placebo. At week 24, both drugs demonstrated over 100% improvement in lesional scalp transcriptome profiles toward a nonlesional state. Brepocitinib showed faster initial effects (week 12), while ritlecitinib had greater long-term improvement (week 24). Hair regrowth (measured by SALT scores) correlated positively with reduced T-cell infiltration and inflammatory markers in scalp tissue.

Study Design

The study was a randomized, double-blind, placebo-controlled phase 2a clinical trial substudy. It included 46 participants with AA: 18 received ritlecitinib, 16 brepocitinib, and 12 placebo. Lesional scalp biopsies and SALT scores were analyzed at baseline, week 12, and week 24. The primary objective was biomarker changes in hair follicle inflammation, with clinical trial registration NCT02974868.

Dosage & Administration

The parent trial evaluated oral ritlecitinib (dose unspecified in summary) and brepocitinib (50 mg daily). Administration duration was 24 weeks, with biomarker assessments at weeks 12 and 24. Placebo groups received matching inactive treatment.

Results & Efficacy

Brepocitinib: Showed greater early improvement in scalp biomarkers at week 12 (specific effect size not quantified).
Ritlecitinib: Demonstrated superior improvement at week 24, with transcriptome profiles exceeding 100% normalization toward nonlesional states.
SALT Scores: Both drugs showed positive correlations between hair regrowth and reduced expression of T-cell markers (e.g., CD8+ T-cells) and inflammatory cytokines (e.g., IFN-γ, IL-15).
Statistical Significance: Improvements were statistically significant vs. placebo (exact p-values not reported in summary), but direct comparisons between ritlecitinib and brepocitinib lacked detailed significance metrics.

Limitations

Small Sample Size: Only 46 participants (12 in placebo), limiting generalizability.
Short Duration: 24 weeks may be insufficient to assess long-term efficacy or relapse.
Exploratory Endpoint: Biomarker changes were secondary outcomes; primary endpoints focused on clinical efficacy.
No Direct Dose Reporting: Specific dosages for ritlecitinib were not detailed in the summary.
Lack of Long-Term Safety Data: Phase 2a design does not address extended safety or maintenance of effects beyond 24 weeks.

Clinical Relevance

This study suggests that JAK/tyrosine kinase inhibition (via ritlecitinib or brepocitinib) may modulate inflammatory pathways in AA, promoting hair regrowth. However, these are investigational pharmaceutical agents, not dietary supplements. Tyrosine as a nutrient (an amino acid precursor to neurotransmitters) is unrelated to the mechanism of JAK/tyrosine kinase inhibitors. Patients should not self-administer tyrosine supplements expecting similar outcomes, as the study does not support such use. Further phase 3 trials are needed to confirm efficacy and safety for AA treatment.

Note: The study focuses on pharmacological inhibition of tyrosine kinases, not supplementation with the amino acid tyrosine. Results are not applicable to tyrosine as a dietary or cognitive-enhancing supplement.