title: Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ClinicalTrials.gov NCT02197455 and NCT02312882.
  
  
  
  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.
authors.affiliation: Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Milène
authors.initials: M
authors.lastname: Kennedy Crispin
authors.affiliation: Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Ko
authors.affiliation: Department of Dermatology.|Department of Pediatrics, and.
authors.forename: Brittany G
authors.initials: BG
authors.lastname: Craiglow
authors.affiliation: Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Shankar
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Urban
authors.affiliation: Department of Dermatology.|Department of Systems Biology, and.
authors.forename: James C
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Dermatology.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Cerise
authors.affiliation: Department of Dermatology.
authors.forename: Ali
authors.initials: A
authors.lastname: Jabbari
authors.affiliation: Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Mårten Cg
authors.initials: MC
authors.lastname: Winge
authors.affiliation: Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: M Peter
authors.initials: MP
authors.lastname: Marinkovich
authors.affiliation: Department of Dermatology.|Department of Genetics and Development, Columbia University, New York, New York, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
authors.affiliation: Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Oro
authors.affiliation: Department of Dermatology.
authors.forename: Brett A
authors.initials: BA
authors.lastname: King
mesh_terms: D000328:Adult; D000368:Aged; D000506:Alopecia Areata / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D014481:United States; D055815:Young Adult
chemical_list: D000075242:Janus Kinase Inhibitors; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib