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Antipsoriatik Tedavide Son Gelişmeler: Bir Güncelleme

Sedef hastalığı, aşırı patolojik özelliklere ve tedavisinin farmakolojik olarak yetersiz kaldığı çok sistemli bir otoimmün hastalık olan kronik inflamatuar bir hastalıktır. Temelinde sedef hastalığı epidermal hücreler, keratinosit hiperproliferasyonu, inflamasyon, dermal kapiller genişleme ve pro-anjiyojenik mekanizmalarla ilişkilidir. Diğer kronik hastalıklarla karşılaştırıldığında, sedef hastalığı olan hastalar ciddi psikolojik strese ve bilişsel işlev bozukluklarına sahip olmakla birlikte daha az fiziksel aktivite ve düşük kaliteli yaşam sürer. Patofizyoloji, sedef hastalığının neden olduğu iltihaplanmanın artmasında ve lokalizasyonunda önemli bir rol oynayan interlökin- (IL) -17, IL-23, tümör nekroz faktörü-alfa (TNF-α), interferon-gama (IFN-γ) ve vasküler endotelyal büyüme faktörü (VEGF) gibi çeşitli aracıların katılımıyla karmaşıktır. Bununla birlikte, sedef hastalığı patofizyolojisi hakkında kesintisiz bilgi edinmek, sedef hastalığının kişiye özgü tedavisinin zorluklarının üstesinden gelmek için keşfedilebilecek yeni terapötik hedefleri belirlememize olanak tanır. Geleneksel tedavide kortikosteroidler, vitamin-D, metotreksat ve siklosporin kullanılır, ancak bu ilaçlar düşük etkinliğe ve ciddi yan etkilere sahiptir ve bazen hastalık komorbiditelerine neden olur. 2016-2019 yılları arasında FDA tarafından onaylanan risankizumab-rza, guselkumab ve tildrakizumab-asmn, gibi IL-23 blokerleri, brodalumab ve ixekizumab gibi IL-17 blokerleri ve TNF-α yı hedefleyen sertolizumab pegol gibi hedefe yönelik yeni biyolojikler, orta ila şiddetli sedef hastalığının tedavisinde devrim yarattı, ancak bu ilaçların düşük hasta uyumuna yol açan birçok yan etkiye sahip oldukları bildirildi. Ters biyoloji mühendisliği ile tasarlanan adalimumab, etanersept ve infliksimab biyobenzerleri de maliyet-etkin olmaları nedeniyle popüler hale gelmektedir. İlaçların yeniden kullanılması, esas olarak eski ilaçlar için yeni tıbbi kullanımların tanımlanmasına odaklanmaktadır. İlacın yeniden kullanılmasının ana odağı, ilaç molekülünün çeşitli hedeflerle nasıl etkileşime girdiği ve farmakolojik etkisini nasıl gerçekleştirdiği ve düşük toksisiteli etkili terapötik ajanlar tasarlamanın yeni olanaklarını ortaya çıkarmasıdır.

Anahtar Kelimeler:

Sedef hastalığı; İlaçların yeniden kullanılması; Damarlanma; Vasküler endotelyal büyüme faktörü; Keratinosit proliferasyonu, TNF-α, IFN- γ, Th-17/Th-23 yolağı.

Recent Advancements in Antipsoriatic Therapy: An Update

Psoriasis is a chronic inflammatory, a multisystem autoimmune disease with extreme pathological features and unsatisfied pharmacotherapeutic needs. Primarily psoriasis is associated with epidermal cells, keratinocyte hyperproliferation, inflammation, dermal capillary dilation, and proangiogenic mechanisms. Compared with other chronic diseases, patients with psoriasis have severe psychological stress and undergo reduced physical activeness, cognitive dysfunctions, and low-quality life. Pathophysiology is complex with the involvement of various mediators like interleukin-(IL)-17, IL-23, tumor necrosis factor-alpha (TNF-α), interferongamma(IFN-γ), and vascular endothelial growth factor (VEGF) that play a significant role in escalation and localizing the inflammation caused in psoriasis. However, acquiring uninterrupted knowledge of psoriasis pathophysiology allows us to identify the novel therapeutic targets that could be explored to overcome personalized psoriasis treatment challenges. Conventional therapy includes corticosteroids, vitamin-D, methotrexate, and cyclosporine, but with low efficacy and severe side effects and sometimes causing disease comorbidities. New biologics approved by FDA during 2016-2019, such as IL-23 blockers risankizumab-rza, guselkumab, and tildrakizumab-asmn, certolizumab pegol targeting TNF-α, IL-17 blockers brodalumab and ixekizumab have revolutionized the treatment of moderate to severe psoriasis due to targeted approach but are reported to possess many side effects leading to low patient compliance. Biosimilars of adalimumab, etanercept, and infliximab, designed by reverse engineering of biologics, are also becoming popular due to their cost-effectiveness. Drug repurposing focuses mainly on defining new medical uses for old drugs. The main focus of drug repurposing is how the drug molecule interacts with various targets and executes its pharmacological action, revealing the new possibilities of designing effective therapeutic agents with low toxicity.

Keywords:

Psoriasis; Drug repurposing, Angiogenesis, Vascular endothelial growth factor Keratinocyte proliferation, TNF-α, IFN-γ, Th-17/Th-23 pathway,

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