Tofacitinib for the treatment of psoriasis.
BACKGROUND
The identification of a number of psoriasis-susceptibility genes and a better understanding of the pathogenesis of the intracellular metabolic pathways, have generated new perspectives on psoriasis treatment, in particular new compounds that inhibit certain intracellular proteins involved in the immune response. In contrast to biologic agents, these compounds block intracellular targets such as transcriptional factors or enzymes.


METHODS
Tofacitinib is a small molecule that acts as a reversible, competitive inhibitor of ATP in the ATP binding site of JAK proteins, determining their inactivation, thus prevents the downstream activation of the STAT proteins, which are then unable to up-regulate the pro-inflammatory genes implicated in psoriasis. The authors present an overview of Phases I - III clinical trials of tofacitinib for psoriasis based on peer-reviewed literature.


CONCLUSIONS
In clinical practice, it is important to assess the response of psoriasis to tofacitinib and identify possible clinical, genetic, and immune biomarkers to predict the response. Comorbidities associated with psoriasis, in particular metabolic syndrome and obesity, are also an important aspect of using tofacitinib in clinical practice. There are some evidences that a drug such as tofacitinib could be used to improve not only psoriasis, but also some of its important comorbidities.
a Department of Dermatology , University of Rome 'Tor Vergata' , Rome , Italy.
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Galluzzo
a Department of Dermatology , University of Rome 'Tor Vergata' , Rome , Italy.
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D'Adamio
a Department of Dermatology , University of Rome 'Tor Vergata' , Rome , Italy.
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Servoli
a Department of Dermatology , University of Rome 'Tor Vergata' , Rome , Italy.
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Bianchi
a Department of Dermatology , University of Rome 'Tor Vergata' , Rome , Italy.
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Chimenti
a Department of Dermatology , University of Rome 'Tor Vergata' , Rome , Italy.
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Talamonti
D015415:Biomarkers / Q000378:metabolism; D004334:Drug Administration Schedule; D006801:Humans; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*
D015415:Biomarkers; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
JAK-STAT pathway; Small molecule drugs; Th17; cytokines; phase III trial; psoriasis