Tofacitinib for the treatment of psoriasis

Galluzzo, Marco; D’Adamio, Simone; Servoli, Stella; Bianchi, Luca; Chimenti, Sergio; Talamonti, Mark S.

doi:10.1080/14656566.2016.1195812

Cited by 26 publications

(8 citation statements)

References 90 publications

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“…Over the past 20 years, our knowledge of the intracellular pathways downstream of cytokine receptors has greatly increased, and the inhibition of intracellular enzymes such as receptor-associated kinases represents a novel way to simultaneously inhibit multiple cytokines. Small orally available molecules can be passively transported through the cellular membrane and block the intracellular activity of their targets [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects

Banerjee¹,

Biehl²,

Gadina³

et al. 2017

Drugs

877

597

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The Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. The success of small-molecule JAK inhibitors (Jakinibs) in the treatment of rheumatologic disease demonstrates that intracellular signaling pathways can be targeted therapeutically to treat autoimmunity. Tofacitinib, the first rheumatologic Jakinib, is US Food and Drug Administration (FDA) approved for rheumatoid arthritis and is currently under investigation for other autoimmune diseases. Many other Jakinibs are in preclinical development or in various phases of clinical trials. This review describes the JAK-STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK-STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK-STAT signaling blockade.

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Section: Introductionmentioning

confidence: 99%

JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects

Banerjee¹,

Biehl²,

Gadina³

et al. 2017

Drugs

877

597

View full text Add to dashboard Cite

show abstract

“…Another potential treatment option is use of a Janus kinase (JAK) inhibitor. This class of medication is quickly gaining recognition as a possible solution for multiple autoimmune conditions including psoriasis, alopecia areata, and IBD [18][19][20][21]. Given the proposed pathogenesis of TNF inhibitor induced alopecia (outlined above), and the fact that JAKs lie downstream of IFN-γ, it follows that JAK inhibitors may be useful for this condition as well.…”

Section: Managementmentioning

confidence: 99%

TNF inhibitor induced alopecia: an unusual form of psoriasiform alopecia that breaks the Renbök mold

Craddock

Cooley²,

Endo³

et al. 2017

Dermatology Online Journal

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TNF-α-inhibitors are known to induce skin adverse effectsincludingpsoriasisandalopeciaareata.Here,we describe a unique pattern of hair loss that has psoriatic and alopecia areata-like features. Diagnosis requires clinical-pathologic correlation and is supported by increased catagen/telogen hairs, psoriasiform epidermal hyperplasia, perifollicular lymphocytic infiltrate, and the presence of eosinophils and plasma cells. Although there are no treatment consensus guidelines, management options include stopping therapy, switching to a different TNF-α inhibitor or ustekinumab (in severe cases), or continuing TNF-α inhibitor therapy with addition of topical, intralesional, or systemic immunosuppressants.

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“…Psoriatic patients are generally treated with glucocorticosteroids and/or conventional immunosuppressants, which could temporarily alleviate symptoms, whereas result in serious side effects (7,8). In recent years, drugs for psoriasis have been screened as target suppression of IL-17A, IL-23, and Janus kinase (JAK), such as ustekinumab, ixekizumab, and tofacitinib, which are well effective but expensive (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway

Guo

Zhuang

et al. 2021

Front. Immunol.

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Psoriasis is a recurrent autoimmune skin disease with aberrant regulation of keratinocytes and immunocytes. There is no universally accepted single treatment available for psoriasis, and the establishment of a common treatment option to control its signs and symptoms is urgently needed. Here, we found Ebosin, a novel exopolysaccharide isolated from Streptomyces sp. 139 by our lab, not only could ameliorate inflammation in LPS-induced keratinocytes through IKK/NF-kapaB pathway, but also attenuate psoriatic skin lesions and reduce inflammatory factors expression in imiquimod (IMQ)-mediated psoriatic mice. Except for inhibiting the expression of epidermal differentiation related proteins, Ebosin significantly increased the percentage of CD4+Foxp3+CD25+ Tregs and decreased CD4+IL17A+ Th17 cells in psoriatic mice. Furthermore, we demonstrate that Ebosin significantly suppressed the IL-17 signaling pathway via A20 (encoded by tnfaip3) in vivo. As the direct binding of tnfaip3 to miR-155 has been demonstrated by luciferase reporter assay, and Ebosin has been demonstrated to inhibit miR-155 level in vitro and in vivo, our study first indicates that Ebosin reduces inflammation through the miR-155-tnfaip3-IL-17 axis and T cell differentiation in a psoriasis-like model. Thus, we conclude that Ebosin can act as a promising therapeutic candidate for the treatment of psoriasis.

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Tofacitinib for the treatment of psoriasis

Cited by 26 publications

References 90 publications

JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects

JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects

TNF inhibitor induced alopecia: an unusual form of psoriasiform alopecia that breaks the Renbök mold

Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway

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