Latest Advances for the Treatment of Chronic Plaque Psoriasis with Biologics and Oral Small Molecules

Bellinato, Francesco; Gisondi, Paolo; Girolomoni, Giampiero

doi:10.2147/btt.s290309

Cited by 37 publications

(41 citation statements)

References 32 publications

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“…Deucravacitinib, formerly known as BMS986165, is an oral selective TYK2 inhibitor. Deucravacitinib uniquely binds to the TYK2 regulatory domain, which allows it to target the underlying pathogenesis of psoriasis through inhibition of the intracellular component of the IL-12, IL-23, and Type I interferon pathways [ 109 , 110 ].…”

Section: Resultsmentioning

confidence: 99%

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The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

Singh

Koppu

Perche

et al. 2021

IJMS

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Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, Th1, Th2, and Th17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis’, the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis’, an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease.

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Section: Resultsmentioning

confidence: 99%

“…Treatment discontinuation due to adverse events was reported in 2 to 7% of patients treated with deucravacitinib across treatment groups, compared to placebo 4% [ 110 ]. Currently, Deucravacitinib is being investigated in multiple phase III clinical trials [ 109 ].…”

Section: Resultsmentioning

confidence: 99%

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

Singh

Koppu

Perche

et al. 2021

IJMS

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“… 89 Among various types of T cells, IL-17-releasing Th17 cells contribute to the development of psoriasis, and the success of drugs that block the IL-23/Th17 axis underscores the importance of Th17 in the pathogenesis of psoriasis. 93 …”

Section: In Vitro Models Of Psoriasismentioning

confidence: 99%

In Vitro Models Mimicking Immune Response in the Skin

2021

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The skin is the first line of defense of our body, and it is composed of the epidermis and dermis with diverse immune cells. Various in vitro models have been investigated to recapitulate the immunological functions of the skin and to model inflammatory skin diseases. The simplest model is a two-dimensional (2D) co-culture system, which helps understand the direct and indirect cell-to-cell interactions between immune and structural cells; however, it has limitations when observing three-dimensional (3D) interactions or reproducing skin barriers. Conversely, 3D skin constructs can mimic the human skin characteristics in terms of epidermal and dermal structures, barrier functions, cell migration, and cell-to-cell interaction in the 3D space. Recently, as the importance of neuro-immune-cutaneous interactions in the inflammatory response is emerging, 3D skin constructs containing both immune cells and neurons are being developed. A microfluidic culture device called “skin-on-a-chip,” which simulates the structures and functions of the human skin with perfusion, was also developed to mimic immune cell migration through the vascular system. This review summarizes the in vitro skin models with immune components, focusing on two highly prevalent chronic inflammatory skin diseases: atopic dermatitis and psoriasis. The development of these models will be valuable in studying the pathophysiology of skin diseases and evaluating the efficacy and toxicity of new drugs.

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“…Psoriasis is currently incurable, and therefore long-term treatments able to cope with the relapsing episodes of the disease are important ( Gisondi et al, 2017 ). Advancements in our understanding of the disease have led to the development of biologics targeting, for example, IL-17 and TNFα ( Bellinato et al., 2021 ), which are used systemically to treat moderate and severe disease. Topical treatment options for milder disease include calcipotriol, which is given either alone or in combination with the corticosteroid betamethasone dipropionate ( Fenton and Plosker, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes

et al. 2021

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Summary Psoriasis is a chronic skin disease, in which immune cells and keratinocytes keep each other in a state of inflammation. It is believed that phospholipase A 2 (PLA 2 )-dependent eicosanoid release plays a key role in this. T-helper (Th) 1-derived cytokines are established activators of phospholipases in keratinocytes, whereas Th17-derived cytokines have largely unknown effects. Logical model simulations describing the function of cytokine and eicosanoid signaling networks combined with experimental data suggest that Th17 cytokines stimulate proinflammatory cytokine expression in psoriatic keratinocytes via activation of cPLA 2 α-Prostaglandin E 2 -EP4 signaling, which could be suppressed using the anti-psoriatic calcipotriol. cPLA 2 α inhibition and calcipotriol distinctly regulate expression of key psoriatic genes, possibly offering therapeutic advantage when applied together. Model simulations additionally suggest EP4 and protein kinase cAMP-activated catalytic subunit alpha as drug targets that may restore a normal phenotype. Our work illustrates how the study of complex diseases can benefit from an integrated systems approach.

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Latest Advances for the Treatment of Chronic Plaque Psoriasis with Biologics and Oral Small Molecules

Cited by 37 publications

References 32 publications

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

In Vitro Models Mimicking Immune Response in the Skin

Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes

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