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JCI Insight. 2016 Sep 22;1(15):e89776. doi: 10.1172/jci.insight.89776.

Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata.

Author information

1
Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
2
Department of Dermatology.
3
Department of Pediatrics, and.
4
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
5
Department of Systems Biology, and.
6
Department of Genetics and Development, Columbia University, New York, New York, USA.

Abstract

BACKGROUND:

Alopecia areata (AA) is an autoimmune disease characterized by hair loss mediated by CD8+ T cells. There are no reliably effective therapies for AA. Based on recent developments in the understanding of the pathomechanism of AA, JAK inhibitors appear to be a therapeutic option; however, their efficacy for the treatment of AA has not been systematically examined.

METHODS:

This was a 2-center, open-label, single-arm trial using the pan-JAK inhibitor, tofacitinib citrate, for AA with >50% scalp hair loss, alopecia totalis (AT), and alopecia universalis (AU). Tofacitinib (5 mg) was given twice daily for 3 months. Endpoints included regrowth of scalp hair, as assessed by the severity of alopecia tool (SALT), duration of hair growth after completion of therapy, and disease transcriptome.

RESULTS:

Of 66 subjects treated, 32% experienced 50% or greater improvement in SALT score. AA and ophiasis subtypes were more responsive than AT and AU subtypes. Shorter duration of disease and histological peribulbar inflammation on pretreatment scalp biopsies were associated with improvement in SALT score. Drug cessation resulted in disease relapse in 8.5 weeks. Adverse events were limited to grade I and II infections. An AA responsiveness to JAK/STAT inhibitors score was developed to segregate responders and nonresponders, and the previously developed AA disease activity index score tracked response to treatment.

CONCLUSIONS:

At the dose and duration studied, tofacitinib is a safe and effective treatment for severe AA, though it does not result in a durable response. Transcriptome changes reveal unexpected molecular complexity within the disease.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02197455 and NCT02312882.

FUNDING:

This work was supported by the US Department of Veterans Affairs Office of Research and Development, National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health grant R01 AR47223 and U01 AR67173, the National Psoriasis Foundation, the Swedish Society of Medicine, the Fernström Foundation, the Locks of Love Foundation, the National Alopecia Areata Foundation, and the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.

PMID:
27699252
PMCID:
PMC5033755
DOI:
10.1172/jci.insight.89776
[Indexed for MEDLINE]
Free PMC Article

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