Treatments for psoriasis: A journey from classical to advanced therapies. How far have we reached?

Hari, Gangadhar; Kishore, Anoop; Pai, K. Sreedhara Ranganath

doi:10.1016/j.ejphar.2022.175147

Cited by 13 publications

(7 citation statements)

References 123 publications

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“…The underlying aetiology is not yet unclear. Evidence suggests the congregation of immune cells and their secreted in ammatory cytokines, leukocytes, and other in ammation-promoting factors in large amounts within the epidermal layers of the skin, driving an in ammatory milieu [20] . The treatment option for patient with psoriasis is based on the severity of the disease and decided by the clinicians with guidelines [21] .…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Immune Subtypes and Potential Hub Genes of Patients with Psoriasis

Tian

et al. 2022

Preprint

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Background Psoriasis is a common, chronic and relapsing immune-related inflammatory dermal disease. Patients with psoriasis suffering from the recurrences is mainly caused by immnue response disorder. Thus, our study is aim to identify novel immnue subtypes and select targeted drugs for the precision therapy in different subtypes of psoriasis. Methods Differentially expressed genes of psoriasis were identified from the Gene Expression Omnibus database. Functional and disease enrichment were performed by Gene Set Enrichment Analysis and Disease Ontology Semantic and Enrichment analysis. Hub genes of psoriasis were selected from protein-protein interaction networks using Metascape database. The expression of hub genes were validated in human psoriasis samples by RT-qPCR and immunohistochemistry. Further, novel immune subtypes of psoriasis were identified by ConsensusClusterPlus package and its association with hub genes were calculated. Immune infiltration analysis were performed and its candidate drugs were evaluated by Connectivity Map analysis. Results 182 differentially expressed genes of psoriasis were identified from GSE14905 corhot, in which 99 genes were significantly up-regulated and 83 genes were down-regulated. We then conducted funtional and disease enrichment in up-regulated genes of psoriasis. Five potential hub genes of psoriasis were obtained, including SOD2, PGD, PPIF, GYS1 and AHCY. The high expression of hub genes were validated in human psoriasis samples. Notably, two novel immune subtypes of psoriasis were determined and defined as C1 and C2. Bioinformatic analysis showed C1 and C2 had different enrichment in immune infiltration cells. Further, candidate drugs and mechanism of action that applicable to different subtypes were evaluated. Conclusion Our study identified two novel immnue subtypes and five potential hub genes of psoriasis. These findings might give insight into the pathogenesis of psoriasis and provide effective immunotherapy regimens for the precise treatment of psoriasis.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Immune Subtypes and Potential Hub Genes of Patients with Psoriasis

Tian

et al. 2022

Preprint

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“…Roflumilast is a selective, highly potent PDE-4 inhibitor with greater affinity for PDE-4 compared with crisaborole and apremilast 18,29 PDE4 is a major cAMP metabolizing enzyme, an intracellular enzyme involved in the regulation of cell proliferation, differentiation, and immune responses, 30,31 Lymphocytes (T cells), macrophages, and dendritic cells express PDE4 enzymes abundantly. 32 PDE4 mediates inflammatory responses, thus playing a role in psoriasis pathogenesis, which involves multiple inflammatory mediators such as TNF-a and IFN-g. Cyclic AMP is considered an universal regulator of cellular function, a signaling molecule that regulates biological responses to external stimuli, involved in a variety of normal cellular responses. 33 Reduced cAMP levels trigger the proinflammatory cascade, whereas increased levels induce antiinflammatory processes.…”

Section: Mechanism Of Action and Pharmacodynamicsmentioning

confidence: 99%

“…The actions of cAMP are mediated through receptors including protein kinase A, cyclic nucleotide-gated channels, and exchange proteins controlled by cAMP (EPACs). Downstream transcription factors include adenylyl cyclase-activating transcription factor-1 and cAMP response element-binding protein (CREB), which downregulates the actions of NFκB signaling, 32 protein kinase A phosphorylation after the increase in cAMP level activate CREB and transcription factor-1. These, in turn, induce the anti-inflammatory cytokine gene expression and inhibit the NF-κB pathway through competition for the coactivators (p300 and CREB binding protein).…”

Section: Mechanism Of Action Pharmacodynamics and Pharmacokineticsmentioning

confidence: 99%

Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis

Nicolas,

Bear,

Kanaan

et al. 2023

American Journal of Therapeutics

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Background: Plaque psoriasis is a chronic dermatologic autoimmune disease that affects adults and children. Roflumilast 0.3% cream is currently the only topical phosphodiesterase 4 inhibitor indicated for the treatment of plaque psoriasis in patients 12 years or older. Pharmacodynamics and Pharmacokinetics: Roflumilast inhibits phosphodiesterase 4 inhibitor enzyme leading to the accumulation of cyclic adenosine monophosphate, which suppresses the inflammatory mediators interferon-γ and tumor necrosis factor-α. Roflumilast, applied once daily, reaches steady state by day 15 and has a half life of approximately 4 days in adults. Roflumilast undergoes extensive hepatic metabolism by cytochrome P450 enzymes and conjugation. Roflumilast is 99% bound to plasma proteins. Clinical Trials: Roflumilast efficacy and safety were evaluated in the DERMIS-1 and DERMIS-2 clinical trials. These identically designed, double-blind, vehicle-controlled phase 3 trials randomized 881 patients to roflumilast 0.3% cream or vehicle, applied once daily for 8 weeks. In DERMIS-1, the Investigator Global Assessment success rate was 42.4% with roflumilast 0.3% cream compared with 6.1% with the vehicle (32.3%–46.9%; P <0.001). Similarly, in DERMIS-2, the Investigator Global Assessment success rate was 37.5% with roflumilast 0.3% cream compared with 6.9% with the vehicle (20.8%–36.9%; P <0.001). Of 881 participants, 1% discontinued treatment with roflumilast cream due to adverse reactions compared with 1.3% treated with vehicle. Urticaria at the application site (0.3%) was the most common adverse reaction that led to discontinuation of roflumilast. Therapeutic Advance: To date, topical corticosteroids are the most commonly used agents to treat mild plaque psoriasis. Sensitive areas are often challenging to treat with existing topical therapy, including corticosteroids. Topical roflumilast has shown to be effective in treating sensitive areas, including skin folds, and may be an alternative to systemic therapy for some patients. The Food and Drug Administration approved topical roflumilast for the treatment of plaque psoriasis, including intertriginous areas, for patients 12 years or older.

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“…"Cyclosporine, an immunosuppressive agent, popularly used in organ transplant patients to prevent immune rejection, surfaced as a very effective treatment for plaque psoriasis. Nevertheless, the long-term use of cyclosporine is thwarted by severe side effects, including renal failure and alterations in blood pressure" [14]. It is only suitable for shortterm use.…”

Section: Traditional Systemic Treatment Of Psoriasismentioning

confidence: 99%

“…"Tumour necrosis factor α (TNFα) is the major cytokine of the Th1 innate immunity pathway" [14]. "The efficacy of TNFα inhibitors is primarily due to their role in preventing the activation of dendritic cells, which produce IL23 and activation of Th17 lineage and its effector molecules (IL17 & IL22).…”

Section: Tnf Inhibitor Studiesmentioning

confidence: 99%

Update Research in Psoriasis

Yan

Wu²,

Jiao³

2022

IJTDH

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Psoriasis is now more recognized as a chronic-lymphocyte mediated inflammatory and proliferous skin disease. In European countries, the prevalence of psoriasis is 1%~3%, so the study of psoriasis is very important. With the study of immune pathogenesis and the progress of genetic engineering technology, it has been gradually developed a wide range of biological agents, And achieved good results in clinical trials or clinical treatment. This paper discusses the typical clinical manifestations, genetic research and treatment of psoriasis.

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Treatments for psoriasis: A journey from classical to advanced therapies. How far have we reached?

Cited by 13 publications

References 123 publications

Identification of Novel Immune Subtypes and Potential Hub Genes of Patients with Psoriasis

Identification of Novel Immune Subtypes and Potential Hub Genes of Patients with Psoriasis

Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis

Update Research in Psoriasis

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