JAK Inhibitor Use Improves Psychiatric, Sleep Outcomes in Alopecia Areata

New findings support the conclusion that the targeting of the inflammatory pathways involved in alopecia areata via Janus Kinase (JAK) inhibitors may lead to reductions in neuroimmune dysregulation and to diminished psychiatric burdens associated with this dysregulation.1

These findings resulted from a recent analysis conducted to evaluate the neuropsychiatric comorbidities that can be prevalent among individuals living with alopecia areata.

Jasmine Levine, from the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, worked alongside a team of investigators in this analysis. Levine et al noted that although JAK inhibitors, sometimes referred to as JAKis, have demonstrated effectiveness in promoting regrowth of hair in alopecia areata within previous research, their therapeutic use in the aforementioned comorbidities had been largely unexamined before this study.2

“This real-world retrospective study utilized the TriNetX Global Collaborative Network to evaluate the effects of JAKis on psychiatric and sleep disorder outcomes in [alopecia areata] patients,” Levine and coauthors wrote.1

The investigators conducted their retrospective analysis by first categorizing patients living with alopecia areata. They did this in April 2025, using ICD-10-CM code L63 and RxNorm and coding into 3 treatment-based cohorts: (1) individuals being treated with JAKis—specifically upadacitinib, ritlecitinib, tofacitinib, baricitinib, or ruxolitinib; (2) individuals given a prescription for traditional non-steroidal immunosuppressants—cyclosporine, methotrexate, azathioprine, or mycophenolate mofetil; and (3) those treated with systemic corticosteroids—methylprednisolone, dexamethasone, prednisolone, or prednisone.

They matched the cohorts were matched 1:1 using propensity scores based on demographics and clinical risk factors. To be considered eligible for this analysis, Levine and colleagues required at least 2 systemic prescriptions.

The investigative team did not include subjects who were shown to have a history of psychiatric or sleep conditions. Over the course of their study, the team implemented Cox proportional hazards models for the purposes of evaluating long-term risk for various neuropsychiatric and sleep-related outcomes.

These outcomes assessed by the investigators included depressive disorders, mood disorders, and anxiety, multiple categories of sleep disorders such as hypersomnia and sleep apnea, ADHD, and utilization of antidepressants.

In their comparisons between the JAK inhibitor cohort (n = 1399; average follow-up: 1544 days) with individuals on non-steroidal immunosuppressants (n = 1399; average follow-up: 2040 days), it was noted that those receiving JAKis had significantly diminished risks for several outcomes:

• Antidepressant prescriptions: HR = 0.778 [95% CI: 0.634, 0.954]
• Non-psychotic mental health disorders: HR = 0.771 [95% CI: 0.619, 0.961]
• Overall sleep disorders: HR = 0.517 [95% CI: 0.395, 0.676]
• Other sleep disorders: HR = 0.241 [95% CI: 0.142, 0.407]
• Sleep apnea specifically: HR = 0.510 [95% CI: 0.341, 0.761]

They highlighted a lack of other neuropsychiatric outcomes that showed statistically significant differences in the comparison between the cohorts.

In a separate comparison conducted between JAKi-treated subjects (n = 1121; mean follow-up: 1368 days) and subjects treated with systemic steroids (n = 1121; mean follow-up: 2153 days), Levine et al revealed that the JAK inhibitor arm of the study had a significantly diminished risk across all of the neuropsychiatric outcomes assessed in the analysis.

In light of the association between alopecia areata and elevated rates of neuropsychiatric conditions recognized, the investigators' findings indicate that treatment using JAK inhibitors may provide patients living with the hair loss condition with a protective effect as opposed to traditional immunosuppressants and as opposed to corticosteroids.

“Study limitations include a retrospective design, reliance on electronic records, and potential residual confounding,” they acknowledged.1 “A lack of data on disease duration, severity, treatment duration, and clinical decision-making may further limit group comparability. Additionally, the relatively short follow-up period may under-estimate long-term psychiatric risk.

References

1. Levine J, Islam RK, Mo L, et al (2025). Impact of Janus Kinase Inhibitors on Psychiatric and Sleep Outcomes in Alopecia Areata: A Real-World Multicenter Cohort Study. Int J Dermatol. https://doi.org/10.1111/ijd.17846.

2. K.-A. L. Dillon, “A Comprehensive Literature Review of JAKInhibitors in Treatment of Alopecia Areata,” Clinical, Cosmetic andInvestigational Dermatology 14 (2021): 691–714, https://doi.org/10.2147/ccid.s309215.