8643e74380cd553b6e5e49b3ffcc1c51 pmc_10892104.pdf 0380487fcee97a1dd014719b9683cb0cd67be48a pmc_10892104.pdf 347bf6140081c1f30a4951e3004fd0ae06b9fa9c593d5eeefcb8440bc10c4613 pmc_10892104.pdf Title: New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis Subject: The introduction of biologic therapies has led to dramatic improvements in the management of moderate-to-severe psoriasis. Even though the efficacy and safety of the newer biologic agents are difficult to match, oral administration is considered an important advantage by many patients. Current research is focused on the development of oral therapies with improved efficacy and safety compared with available alternatives, as exemplified by deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for the treatment of moderate to severe psoriasis in adults. Recent advances in our knowledge of psoriasis pathogenesis have also led to the development of targeted topical molecules, mostly focused on intracellular signaling pathways such as AhR, PDE-4, and Jak-STAT. Tapinarof (an AhR modulator) and roflumilast (a PDE-4 inhibitor) have exhibited favorable efficacy and safety outcomes and have been approved by the FDA for the topical treatment of plaque psoriasis. This revision focuses on the most recent oral and topical therapies available for psoriasis, especially those that are currently under evaluation and development for the treatment of psoriasis. Keywords: psoriasis; oral therapies; topical therapies; biologics; Jak inhibitors; PDE4 inhibitors; systemic treatment; IL-17 inhibitors; IL-23 inhibitors; tapinarof; roflumilast Author: Elena Carmona-Rocha, Lluís Rusiñol and Lluís Puig Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Feb 9 04:30:13 2024 CET ModDate: Fri Feb 9 04:38:57 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 36 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1114059 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- PSUYZB+VnURWPalladioL Type 1 Custom yes yes no 10 0 UXVUML+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 MEITOV+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 XTUJQZ+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 LHCXDL+EURM10 Type 1 Builtin yes yes no 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PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methods Destination: section.2 Item: Title: Emerging Oral Treatments for Psoriasis Destination: section.3 Children: Item: Title: Jak Inhibitors Destination: subsection.3.1 Children: Item: Title: Tofacitinib Destination: subsubsection.3.1.1 Item: Title: Abrocitinib Destination: subsubsection.3.1.2 Item: Title: Baricitinib Destination: subsubsection.3.1.3 Item: Title: Peficitinib Destination: subsubsection.3.1.4 Item: Title: Solcitinib (GSK2586184) Destination: subsubsection.3.1.5 Item: Title: Itacitinib Adipate Destination: subsubsection.3.1.6 Item: Title: Brepocitinib Destination: subsubsection.3.1.7 Item: Title: Ropsacitinib Destination: subsubsection.3.1.8 Item: Title: Deucravacitinib Destination: subsubsection.3.1.9 Item: Title: BMS-986202 Destination: subsubsection.3.1.10 Item: Title: SAR-20347 Destination: subsubsection.3.1.11 Item: Title: Zasocitinib (TAK-279) Destination: subsubsection.3.1.12 Item: Title: VTX958 Destination: subsubsection.3.1.13 Item: Title: Oral PDE4 Inhibitors Destination: subsection.3.2 Children: Item: Title: Oral TNF Inhibitors Destination: subsubsection.3.2.1 Item: Title: Oral IL-17 Inhibitors Destination: subsubsection.3.2.2 Item: Title: Oral IL-23 Inhibitors Destination: subsection.3.3 Item: Title: RORT Inhibitors Destination: subsection.3.4 Item: Title: Sphingosine-1-Phosphate Receptor 1 Antagonist Destination: subsection.3.5 Item: Title: A3 Adenosine Receptor Agonist Destination: subsection.3.6 Item: Title: Heat Shock Protein 90 Destination: subsection.3.7 Item: Title: ROCK-2 Inhibitor Destination: subsection.3.8 Item: Title: Current and Emerging Topical Treatments for Psoriasis Destination: section.4 Children: Item: Title: Aryl Hydrocarbon Receptor (AhR) Modulators Destination: subsection.4.1 Item: Title: Phosphodiesterase Type-4 (PDE-4) Inhibitors Destination: subsection.4.2 Children: Item: Title: Topical Roflumilast Destination: subsubsection.4.2.1 Item: Title: Topical Crisaborole Destination: subsubsection.4.2.2 Item: Title: Janus Kinase (Jak) Inhibitors Destination: subsection.4.3 Children: Item: Title: Topical Tofacitinib Destination: subsubsection.4.3.1 Item: Title: Topical Ruxolitinib Destination: subsubsection.4.3.2 Item: Title: Topical Brepocitinib Destination: subsubsection.4.3.3 Item: Title: Potential Future Targets for Topical Therapy Destination: subsection.4.4 Children: Item: Title: Topical ROR Inverse Agonists Destination: subsubsection.4.4.1 Item: Title: Interleukin-2 (IL-2) Inhibitors Destination: subsubsection.4.4.2 Item: Title: RNA Modulation Destination: subsubsection.4.4.3 Item: Title: Amygdalin Analogue Destination: subsubsection.4.4.4 Item: Title: Discussion Destination: section.5 Item: Title: Conclusions and Future Directions Destination: section.6 Item: Title: References Destination: section.7 Info: Title: New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis Author: Elena Carmona-Rocha, Lluís Rusiñol and Lluís Puig Subject: The introduction of biologic therapies has led to dramatic improvements in the management of moderate-to-severe psoriasis. Even though the efficacy and safety of the newer biologic agents are difficult to match, oral administration is considered an important advantage by many patients. Current research is focused on the development of oral therapies with improved efficacy and safety compared with available alternatives, as exemplified by deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for the treatment of moderate to severe psoriasis in adults. Recent advances in our knowledge of psoriasis pathogenesis have also led to the development of targeted topical molecules, mostly focused on intracellular signaling pathways such as AhR, PDE-4, and Jak-STAT. Tapinarof (an AhR modulator) and roflumilast (a PDE-4 inhibitor) have exhibited favorable efficacy and safety outcomes and have been approved by the FDA for the topical treatment of plaque psoriasis. This revision focuses on the most recent oral and topical therapies available for psoriasis, especially those that are currently under evaluation and development for the treatment of psoriasis. 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