Predictive Factors for Treatment Responses to Baricitinib in Severe Alopecia Areata: A Retrospective Multivariate Analysis

Academic Background

Alopecia Areata (AA) is a chronic autoimmune skin disease characterized by non-scarring hair loss. Its pathogenesis involves an abnormal immune attack on hair follicles, leading to hair loss. In recent years, Janus kinase inhibitors (JAK inhibitors, JAKi) have shown potential in the treatment of AA, particularly Baricitinib, which inhibits the JAK-STAT signaling pathway, thereby preventing inflammatory responses targeting hair follicles. Although Baricitinib has demonstrated significant efficacy in AA treatment, patient responses vary widely, and the predictive factors for these responses remain incompletely understood. This study aims to identify independent predictors of Baricitinib efficacy in severe AA through multivariate analysis, providing more precise guidance for clinical treatment.

Paper Source

This study was conducted by a research team from the Department of Dermatology at Tohoku University Graduate School of Medicine, led by authors including Moyuka Wada-Irimada and Takehiro Takahashi. The study was published in the Journal of Dermatology in 2025, with the DOI 10.¹¹¹¹⁄₁₃₄₆-8138.17641.

Research Process

Study Subjects and Data Collection

This retrospective study analyzed the medical records of 70 patients with severe AA who started Baricitinib treatment at Tohoku University Hospital between July 2022 and August 2023. All patients had a baseline Severity of Alopecia Tool (SALT) score ≥50 and had not experienced hair regrowth within the preceding 6 months. Patients had previously received treatments such as topical steroids, intravenous methylprednisolone pulse (IVMP) therapy, or topical immunotherapy. The primary outcome measure was the proportion of patients achieving a SALT score ≤20 after 9 months of treatment.

Clinical Information Collection

Th e res earch t eam c oll ec t ed e ight c linica l v ariables , including t ype o f AA (multiplex alopecia areata, alopecia totalis, alopecia universalis, ophiasis alopecia), sex, age, disease duration, history of atopic dermatitis, IVMP treatment history, pre-treatment SALT score, and clinician-reported outcome (ClinRO) scores for eyebrows and eyelashes.

Data Analysis Methods

Multivariate logistic regression analysis and least-squares regression analysis were used to assess the impact of different background factors on Baricitinib treatment responses. The study set achieving a SALT score ≤20 as the primary endpoint and calculated the SALT improvement rate, defined as (pre-treatment SALT score—post-treatment SALT score at 9 months)/pre-treatment SALT score. Statistical analysis was performed using JMP Pro 17 software, with a significance level set at p<0.05.

Key Findings

Treatment Response Rate

Among the 70 patients who completed 9 months of Baricitinib treatment, 41% (29 patients) achieved a SALT score ≤20, consistent with the results of Baricitinib’s phase III clinical trials. By AA subtype, patients with multiplex AA (AM) showed the highest response rate (90.9%), while those with ophiasis AA (OA) had the lowest response rate (30%).

Independent Predictive Factors

Multivariate analysis identified the following factors as independent predictors of positive treatment outcomes: 1. Shorter disease duration (≤4 years): Patients with a shorter disease duration were more likely to achieve a SALT score ≤20 compared to those with a longer duration (>4 years) (OR=8.11; p=0.041). 2. History of IVMP treatment: Patients who had received IVMP treatment were more likely to achieve a SALT score ≤20 (OR=10.45; p=0.016). 3. Female patients: Female patients showed significantly higher improvement rates than males (β=10.16; p=0.015). 4. Lower pre-treatment SALT score: Patients with a pre-treatment SALT score ≥95 were less likely to achieve a SALT score ≤20 (OR=0.013; p=0.040).

Differences by AA Subtype

Patients with ophiasis AA (OA) had the poorest treatment response, with significantly lower improvement rates compared to other subtypes (β=-24.72; p=0.029). In patients with alopecia totalis (AT) and alopecia universalis (AU), treatment responses were polarized, with some patients showing complete hair regrowth while others exhibited minimal response.

Safety Analysis

Among the 86 patients who received Baricitinib treatment, 25.6% experienced adverse events (AEs), the most common being a decline in estimated glomerular filtration rate (eGFR) (18.6%) and elevated liver enzymes (3.5%). All AEs were mild, and no grade 3 or 4 AEs were observed.

Research Conclusions

This study, through multivariate analysis, identified independent predictors of Baricitinib efficacy in severe AA, including disease duration, IVMP treatment history, pre-treatment SALT score, and sex. It also found that patients with ophiasis AA (OA) had the poorest response to Baricitinib, highlighting the unique clinical behavior of this subtype. Additionally, female patients showed significantly better treatment responses than males, providing a new direction for future research. The findings offer important insights for clinical decision-making and lay the foundation for further research into the etiology and treatment mechanisms of AA.

Research Highlights

1. First systematic identification of predictive factors: This study is the first to systematically identify independent predictors of Baricitinib treatment responses in AA through multivariate analysis, filling a gap in this research area.
2. Impact of AA subtype on treatment response: The study revealed significant differences in Baricitinib responses based on AA subtypes, particularly the poor response in patients with ophiasis AA, suggesting unique pathological mechanisms in this subtype.
3. Discovery of sex-based differences: Female patients showed significantly better treatment responses than males, providing new clues for future immune mechanism research.
4. Safety validation: The study confirmed the safety of Baricitinib in real-world settings, with all AEs being mild, further supporting its clinical application.

Research Value

This study not only provides clinicians with predictive tools for Baricitinib treatment in AA but also offers new perspectives on the pathological mechanisms of AA. The poor response in patients with ophiasis AA suggests distinct immune-pathological mechanisms in this subtype, warranting further investigation. Additionally, the sex-based differences open new avenues for immune research in AA. These findings hold significant scientific value and provide a basis for personalized treatment approaches for AA patients.