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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Dermatology".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 10858

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Special Issue Editor

Dr. Yozo Ishiuji

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Guest Editor

Department of Dermatology, The Jikei University School of Medicine, Tokyo 105-8461, Japan
Interests: dermatology; dermatopathology; psoriasis

Special Issue Information

Dear Colleagues,

This Special Issue is dedicated to exploring the topic of targeted treatment in psoriasis. The goal of this Special Issue is to gather research papers that highlight recent advancements and novel strategies for treating psoriasis.

We are excited to receive original research articles that focus on the mechanisms of action, safety, and clinical outcomes of targeted therapies for psoriasis. Specifically, we welcome papers that explore the use of biological agents, small molecules, and other innovative drugs that target specific pathways involved in psoriasis pathogenesis.

It is important to note that we will not be accepting mini-reviews or case reports for submission in this Special Issue. Instead, we encourage authors to submit their original research findings that provide valuable insights into new and emerging treatments for psoriasis.

Overall, this Special Issue aims to expand our knowledge and understanding of targeted treatments in psoriasis and to promote the development of more effective and personalized therapies for this chronic disease. We look forward to receiving your submissions and helping to advance the field of psoriasis research.

Dr. Yozo Ishiuji
Guest Editor

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Keywords

prognosis
dermatology
treatment efficacy
immunotherapy
personalized medicine
Koebner phenomenon
phototherapy
combination therapy

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Published Papers (6 papers)

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Research

10 pages, 610 KiB

Open AccessArticle

Long-Term Efficacy and Safety of Guselkumab in Psoriasis Patients Who Failed Anti-IL17: A Two-Year Real-Life Study

by Matteo Megna, Angelo Ruggiero, Fabrizio Martora, Ylenia Vallone, Gianluca Guerrasio and Luca Potestio

J. Clin. Med. 2024, 13(9), 2691; https://doi.org/10.3390/jcm13092691 - 3 May 2024

Cited by 1 | Viewed by 1384

Abstract

Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of interleukin (IL)-23. Despite its effectiveness and safety, which have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 are limited or characterized by a reduced follow-up period. These data are essential to guide clinicians in biologic switching, considering that anti-IL23 and anti-IL17 partially share their therapeutic targets, as well as some patients who may have to interrupt treatment with anti-IL17 for loss of efficacy over time or the development of adverse events (AEs). In this context, we performed a retrospective study with the aim of evaluating the long-term use (2 years) of guselkumab in psoriasis patients who previously failed at least one anti-IL17 in a real-life setting, also focusing attention on psoriasis located in difficult-to-treat areas (the scalp, palms or soles, fingernails, genitals). A total of 61 patients (35 male, 57.4%; mean age 57.6 ± 8.8 years) were enrolled. Of these, 30 (49.2%) patients failed secukinumab, 21 (34.4%) failed ixekizumab, 7 (11.5%) failed brodalumab, and 3 (4.9%) failed both secukinumab and ixekizumab. At the baseline, the mean PASI and BSA were 12.8 ± 8.4 and 24.5 ± 26.6, respectively. During week 16, PASI90 and PASI100 responses were achieved by 60.7% and 37.7% of patients, respectively, which continued to improve up to week 104 (PASI90: 73.8%, PASI100: 59.0%). Clinical improvement in difficult-to-treat areas was detected as well. In particular, a slower improvement for fingernails and the palmoplantar region was reported compared to scalp and genital psoriasis at week 16. However, no differences were found following 28 weeks of therapy. Primary and secondary inefficacy were reported by 1 (1.6%) and 5 (8.2%) patients. As regards safety, no severe AEs were collected. Full article

(This article belongs to the Special Issue Targeted Treatment in Psoriasis)

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9 pages, 1696 KiB

Open AccessArticle

Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study

by Matteo Megna, Anna Balato, Stefano Caccavale, Sara Cacciapuoti, Giulia Calabrese, Eugenia Veronica Di Brizzi, Luisa Di Costanzo, Raffaella Manzo, Vincenzo Marino, Rosa Valentina Puca, Francesca Romano, Oriele Sarno, Genoveffa Scotto di Luzio and Serena Lembo

J. Clin. Med. 2024, 13(9), 2552; https://doi.org/10.3390/jcm13092552 - 26 Apr 2024

Cited by 2 | Viewed by 1612

Abstract

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment. Full article

(This article belongs to the Special Issue Targeted Treatment in Psoriasis)

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9 pages, 664 KiB

Open AccessArticle

Interclass Switch between IL17 and IL23 Inhibitors in Psoriasis: A Real-Life, Long-Term, Single-Center Experience

by Silvia Giordano, Paolo Dapavo, Michela Ortoncelli, Elena Stroppiana, Anna Verrone, Pietro Quaglino, Simone Ribero and Luca Mastorino

J. Clin. Med. 2023, 12(24), 7503; https://doi.org/10.3390/jcm12247503 - 5 Dec 2023

Cited by 3 | Viewed by 1808

Abstract

Background: Interleukin 23 (IL-23) inhibitors, such as guselkumab, risankziumab, and tildrakizumab, have proved to be highly effective and safe for psoriasis treatment either in bio-naïve or bio-experienced patients. A substantial proportion of patients show a primary or secondary inefficacy to IL-17 inhibitors and can benefit from an alternative line of treatment, like IL-23 inhibitors. To date, no sufficient data are available on the effectiveness of IL-23 inhibitors after an anti-IL-17 agent. Methods: Our study includes 48 patients with moderate to severe psoriasis undergoing a switch from IL-17 to IL-23 inhibitors. This trial is registered with SS_DERMO_20. Results: The mean PASI (Psoriasis Area Severity Index) decreases from 11.6 to 3.3 at week 16, with responses maintained at weeks 28 and 52 (2 and 1.4, respectively), and a PASI100 achievement in more than 24% of patients at 16 weeks and 61.9 at 48 weeks, with no occurrence of serious adverse events. However, almost one in six patients interrupted the IL-23 inhibitors mainly due to primary ineffectivenss. Conclusions: Our data support the evidence that an interclass switch among IL-17 inhibitors is a safe and effective therapeutic option for these patients. Full article

(This article belongs to the Special Issue Targeted Treatment in Psoriasis)

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12 pages, 3834 KiB

Open AccessArticle

Aging Impact in Response to Different Classes of Biological Treatment in Psoriatic Patients: A Real-Life Observational Study

by Francois Rosset, Luca Mastorino, Paolo Dapavo, Michela Ortoncelli, Pietro Quaglino and Simone Ribero

J. Clin. Med. 2023, 12(23), 7215; https://doi.org/10.3390/jcm12237215 - 21 Nov 2023

Cited by 1 | Viewed by 1321

Abstract

Over the last decade, the treatment landscape for moderate to severe psoriasis has undergone transformative changes with the advent of biotechnological drugs. Monoclonal antibodies targeting the IL-17 and IL-23 pathways have displayed remarkable clinical efficacy and safety, even among patients with complex comorbidities. These innovations have extended across various age groups within the psoriatic population. However, a scarcity of age-specific data remains regarding the efficacy and safety of these medications. Our study tries to bridge this gap by systematically presenting data obtained from the analysis of 1055 patients treated for psoriasis with anti-IL17 and anti-IL23 drugs during a 1-year period. The effectiveness and safety of anti-IL-17 and anti-IL23 drugs for moderate to severe psoriasis were assessed across four different age groups ranging from patients less than 26 years old to patients older than 65 years, divided in four year ranges. In the studied population, baseline PASI score was significantly higher in the age group of individuals over 65 years compared to those under 26 years old. Patients over 65 years also exhibited a slower rate of improvement in PASI-90 and PASI < 3 at the 16-week mark compared to other age groups. However, no clinically significant differences in treatment response were found when comparing overall responses among different age groups. In age groups older than 26 years, anti-IL17 drugs seems faster in the achievement of PASI-100 when compared to anti-IL23 drugs. This trend became more pronounced with increasing age. The investigation provides insights into treatment responses and patient characteristics, highlighting the influence of age as a significant variable in patient management. Full article

(This article belongs to the Special Issue Targeted Treatment in Psoriasis)

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12 pages, 4929 KiB

Open AccessArticle

Exploring Psoriasis Inflammatory Microenvironment by NanoString Technologies

by Alessia Andrea Ricci, Paolo Dapavo, Luca Mastorino, Gabriele Roccuzzo, Samanta Wolff, Simone Ribero, Paola Cassoni, Rebecca Senetta and Pietro Quaglino

J. Clin. Med. 2023, 12(21), 6820; https://doi.org/10.3390/jcm12216820 - 28 Oct 2023

Cited by 3 | Viewed by 1540

Abstract

Psoriasis is a chronic inflammatory skin disease whose molecular mechanisms and microenvironment are poorly understood. We performed gene expression analysis through the nCounter^® PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA) on 22 FFPE punch biopsies from 19 psoriasis-affected patients. A subset of five cases was analyzed before (T0) and after 6 months (T6) of treatment with dimethyl fumarate (DMF) to address immune microenvironment changes. Molecular comparisons according to biopsy site and age of onset showed a different distribution of innate immune cells (mast cells, macrophages, NK cells, and DC cells) and pathways (complement regulation and transporter functions). The analysis according to PASI (Psoriasis Area and Severity Index) led to non-significant results, suggesting no link between molecular expression profile and clinical amount of skin disease. In DMF-treated patients, we observed a strong immunomodulatory effect after treatment: A subversion of exhausted CD8 T cells, NK CD56dim cells, Tregs, neutrophils, CD45+ cells, T cells, B cells, and macrophages was reported between the two analyzed time-points, as well as the reduction in pro-inflammatory pathways and molecules, including cytotoxicity, pathogen defense, antigen processing, adhesion, cell cycle, chemokines, cytokines, and interleukins. The inflammatory psoriatic microenvironment can be modulated using DMF with encouraging results, achieving an immune-tolerant and non-inflammatory condition through the regulation of both innate and adaptive immunity. Full article

(This article belongs to the Special Issue Targeted Treatment in Psoriasis)

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12 pages, 2771 KiB

Open AccessArticle

The Expression of Activation Markers CD25 and CD69 Increases during Biologic Treatment of Psoriasis

by Michał Adamczyk, Joanna Bartosińska, Dorota Raczkiewicz, Małgorzata Kowal, Agata Surdacka, Danuta Krasowska, Anna Michalak-Stoma and Dorota Krasowska

J. Clin. Med. 2023, 12(20), 6573; https://doi.org/10.3390/jcm12206573 - 17 Oct 2023

Cited by 5 | Viewed by 2766

Abstract

CD (cluster of differentiation) 69 and CD25 are considered early and late markers of the activation of lymphocytes, respectively. CD25 is a part of the IL-2 receptor and is present on the surface of immune and non-immune cells, with high amounts on activated lymphocytes and regulatory T cells. CD69 is expressed on various types of white blood cells, including newly activated lymphocytes, lymphocytes infiltrating tissues isolated from subjects with chronic auto-inflammatory diseases, several subtypes of memory T cells and regulatory T cells. Primarily, CD69 was considered to be an early marker of the activation of lymphocytes, but, right now, data derived from in vitro and in vivo studies have revealed the immunomodulatory role of this surface antigen. In 84 patients with psoriasis, of whom 28 were treated with different biologic drugs, as well as in 29 healthy control subjects, the expression of CD25 and CD69 on different subtypes of peripheral blood mononuclear cells (PBMCs) was studied with the use of flow cytometry. Significantly higher levels of CD3/CD69-, CD8/CD69- and CD19/CD69-positive PBMCs as well as within CD3+ cells were present in subjects suffering from psoriasis when compared to healthy controls. In patients with psoriasis who were treated with biologic drugs, the levels of CD3/CD69-, CD4/CD69- and CD19/CD69-positive PBMCs, and CD3/CD69 within CD3+ cells, CD4/CD69 within CD4+ cells, CD4/CD25 within CD4+ cells and CD19/CD69 within CD19+ cells were significantly higher than before therapy. Our results support a role for activation markers, especially CD69, in psoriasis. Further research is warranted to fully clarify their significance in this common dermatosis, especially during biologic treatment. Full article

(This article belongs to the Special Issue Targeted Treatment in Psoriasis)

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