New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis.

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.

Durability and long-term outcomes of biologic therapies in psoriasis.

INTRODUCTION: Significant advances in psoriasis treatment have taken place since the introduction of biologics. Tumor necrosis factor inhibitors were the first class of biologics approved and at that time greatly improved psoriasis treatment. However, newer biologics, directed to interleukin(IL)-23/IL-17 pathways central to psoriasis pathogenesis, have improved complete or nearly complete clearance rates and are characterized by an excellent safety profile.Real-world setting experiences have generally confirmed the results of clinical trials, but real-world data regarding newer biologics is relatively scarce. AREAS COVERED: We provide an extensive review of real-world survival of biologic treatments for moderate to severe psoriasis. EXPERT OPINION: There is growing and consistent evidence of higher drug survival of IL-23 inhibitors, possibly due to their favorable efficacy and safety profiles, dosing convenience and persistence of response despite treatment interruption; eventual confirmation of their potential role as modifiers of the natural history of psoriasis might provide additional reasons for therapeutic persistence of this class of biologics.

Ixekizumab for the treatment of moderate-to-severe plaque psoriasis: the first septennium.

Ixekizumab is a humanized monoclonal antibody that specifically inhibits IL-17A. It has been approved for the treatment of adult and pediatric psoriasis, psoriatic arthritis and axial spondyloarthropathies by the US FDA and the EMA. Phase III trials, post hoc analyses and real-life data have reported its efficacy, effectiveness and safety. This review summarizes the latest evidence on the clinical efficacy, pharmacology and safety profile of ixekizumab for the treatment of moderate-to-severe psoriasis. A literature search was performed for articles published through December 2022. Ixekizumab is one of the most efficacious biologics for psoriasis, with a rapid onset of response, favorable long-term outcomes and an adequate safety profile.

Ixekizumab is a biologic therapy, a type of disease treatment that uses substances from living organisms, currently available for the treatment of psoriasis. It works as an antibody directed against a molecule that causes inflammation, named IL-17A, which is essential for the development of psoriasis lesions. Ixekizumab has been approved by the US FDA and EMA for the treatment of psoriasis, psoriatic arthritis and axial spondyloarthropathies in adults and children. Its effectiveness and safety have been widely proven in multiple clinical trials and real-life settings. This review summarizes the latest evidence on the clinical efficacy, pharmacology and safety profile of ixekizumab for the treatment of moderate-to-severe psoriasis.

The biological basis of disease recurrence in psoriasis.

Despite the amazing advances produced in our understanding of the pathogenesis of psoriasis, which have led to a therapeutic revolution, our knowledge of the mechanisms of relapse and elicitation of lesions is just starting to unravel. This narrative review tours the different cell types and mechanisms involved in the priming, maintenance, and relapse of psoriasis vulgaris. Our discussion includes dendritic cells, T cells, tissue resident memory cells and mast cells, with a foray into the epigenetic mechanisms of inflammatory memory in keratinocytes. Increasing knowledge is providing a glimpse of a potential therapeutic window of opportunity in psoriasis, providing long term remission and eventual modification of the natural history of the disease.

Psoriasis: a focus on upcoming oral formulations.

INTRODUCTION: Targeted therapies have greatly improved the quality of life of patients with psoriasis. Despite the extensive list of treatments available, multiple new drugs are being developed, especially oral therapies with potential advantages as regards comfort of administration. However, the efficacy and safety of these new oral therapies need to be improved to match those of novel biologics. AREAS COVERED: We provide a narrative review of the oral therapies for psoriasis that are currently under development, from Jak inhibitors to oral IL-17 and IL-23 inhibitors, among others. A literature search was performed for articles published from 1 January 2020, to 6 June 2023. EXPERT OPINION: The approval of deucravacitinib, the first Jak inhibitor for the treatment of moderate-to-severe plaque psoriasis, heralds a bright therapeutic future with multiple new oral formulations. A great number of oral treatments with singular mechanism of action, like A3AR agonists, HSP90 inhibitors, ROCK-2 inhibitors, oral TNF inhibitors, oral IL-23 inhibitors, oral IL-17 inhibitors, PD4 inhibitors (orismilast) and several Tyk2 inhibitors, are currently being evaluated in clinical trials and could be suitable for approval in the future. Growing variation in treatment modes of administration will allow dermatologists to better integrate patient preferences in the therapeutic decision process.

Usefulness of Two Independent DNA and RNA Tissue-Based Multiplex Assays for the Routine Care of Advanced NSCLC Patients.

Personalized medicine is nowadays a paradigm in lung cancer management, offering important benefits to patients. This study aimed to test the feasibility and utility of embedding two multiplexed genomic platforms as the routine workup of advanced non-squamous non-small cell lung cancer (NSCLC) patients. Two parallel multiplexed approaches were performed based on DNA sequencing and direct digital detection of RNA with nCounter® technology to evaluate gene mutations and fusions. The results were used to guide genotype-directed therapies and patient outcomes were collected. A total of 224 advanced non-squamous NSCLC patients were prospectively included in the study. Overall, 85% of samples were successfully characterized at DNA and RNA levels and oncogenic drivers were found in 68% of patients, with KRAS, EGFR, METΔex14, BRAF, and ALK being the most frequent (31%, 19%, 5%, 4%, and 4%, respectively). Among all patients with complete genotyping results and follow-up data (n = 156), the median overall survival (OS) was 1.90 years (confidence interval (CI) 95% 1.69-2.10) for individuals harbouring an actionable driver treated with a matched therapy, compared with 0.59 years (CI 95% 0.39-0.79) in those not eligible for any targeted therapy and 0.61 years (CI 95% 0.12-1.10) in patients with no drivers identified (p < 0.001). Integrating DNA and RNA multiplexing technologies into the routine molecular testing of advanced NSCLC patients is feasible and useful and highlights the necessity of widespread integrating comprehensive molecular diagnosis into lung cancer care.