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An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis

Jabbari, A. ; Sansaricq, F. ; Cerise, J. ; Chen, J.C. ; Bitterman, A. ; Ulerio, G. ; Borbon, J. ; Clynes, R. ; Christiano, A.M. ; Mackay-Wiggan, J.

Journal of investigative dermatology, 2018-07, Vol.138 (7), p.1539-1545 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis
Autor: Jabbari, A. ; Sansaricq, F. ; Cerise, J. ; Chen, J.C. ; Bitterman, A. ; Ulerio, G. ; Borbon, J. ; Clynes, R. ; Christiano, A.M. ; Mackay-Wiggan, J.
Assuntos: Adult ; Alopecia Areata - diagnostic imaging ; Alopecia Areata - drug therapy ; Alopecia Areata - immunology ; Alopecia Areata - pathology ; Autoimmune Diseases - diagnosis ; Autoimmune Diseases - drug therapy ; Autoimmune Diseases - immunology ; Biopsy ; Dose-Response Relationship, Drug ; Female ; Gene Expression Profiling ; Hair Follicle - drug effects ; Hair Follicle - growth & development ; Hair Follicle - pathology ; Humans ; Janus Kinase Inhibitors - pharmacology ; Janus Kinase Inhibitors - therapeutic use ; Janus Kinases - antagonists & inhibitors ; Janus Kinases - immunology ; Male ; Middle Aged ; Nitriles ; Photography ; Pilot Projects ; Piperidines - pharmacology ; Piperidines - therapeutic use ; Pyrazoles - pharmacology ; Pyrazoles - therapeutic use ; Pyrimidines - pharmacology ; Pyrimidines - therapeutic use ; Pyrroles - pharmacology ; Pyrroles - therapeutic use ; Severity of Illness Index ; Treatment Outcome ; Young Adult
É parte de: Journal of investigative dermatology, 2018-07, Vol.138 (7), p.1539-1545
Descrição: Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ∼2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss. The prognosis of AA is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Because these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors. In preclinical trials in mice, tofacitinib successfully prevented AA development and reversed established disease. In our tofacitinib trial in 12 patients with moderate to severe AA, 11 patients completed a full course of treatment with minimal adverse events. Following limited response to the initial dose (5 mg b.i.d.), the dose was escalated (10 mg b.i.d.) for nonresponding subjects. Eight of 12 patients demonstrated ≥50% hair regrowth, while three patients demonstrated <50% hair regrowth, as measured by Severity in Alopecia Tool scoring. One patient demonstrated no regrowth. Gene expression profiles and Alopecia Areata Disease Activity Index scores correlated with clinical response. Our open-label studies of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate to severe AA, providing strong rationale for larger clinical trials using JAK inhibitors in AA. ClinicalTrials.gov ID NCT02299297.
Editor: United States: Elsevier Inc
Idioma: Inglês

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An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis

Jabbari, A. ; Sansaricq, F. ; Cerise, J. ; Chen, J.C. ; Bitterman, A. ; Ulerio, G. ; Borbon, J. ; Clynes, R. ; Christiano, A.M. ; Mackay-Wiggan, J.

United States: Elsevier Inc

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