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Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.

ABSTRACT: Alopecia areata (AA) is an autoimmune disease resulting in hair loss with devastating psychosocial consequences. Despite its high prevalence, there are no FDA-approved treatments for AA. Prior studies have identified a prominent interferon signature in AA, which signals through JAK molecules.A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome. In vivo, preclinical studies were conducted using the C3H/HeJ AA mouse model to assess the mechanism of clinical improvement by baricitinib.The patient exhibited a striking improvement of his AA on baricitinib over several months. In vivo studies using the C3H/HeJ mouse model demonstrated a strong correlation between resolution of the interferon signature and clinical improvement during baricitinib treatment.Baricitinib may be an effective treatment for AA and warrants further investigation in clinical trials.

SUBMITTER: Jabbari A

PROVIDER: S-EPMC4486197 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.

Jabbari Ali A Dai Zhenpeng Z Xing Luzhou L Cerise Jane E JE Ramot Yuval Y Berkun Yackov Y Sanchez Gina A Montealegre GA Goldbach-Mansky Raphaela R Christiano Angela M AM Clynes Raphael R Zlotogorski Abraham A

EBioMedicine 20150226 4

<h4>Background</h4>Alopecia areata (AA) is an autoimmune disease resulting in hair loss with devastating psychosocial consequences. Despite its high prevalence, there are no FDA-approved treatments for AA. Prior studies have identified a prominent interferon signature in AA, which signals through JAK molecules.<h4>Methods</h4>A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome. In vivo, preclinical st ...[more]

PMID: 26137574

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Project description:BackgroundAlopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens.MethodsWe have developed a Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the "educated" autologous cells to the patient's circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years).ResultsClinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a "ring of transforming growth factor beta 1 (TGF-β1)" around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β(+)NKG2D(+) effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs.ConclusionsCurrent clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in subjects with moderate or severe AA.Trial registrationClinicalTrials.gov, NCT01673789, 21 August 2012.

Dataset Information

Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.

Publications

Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.

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