Therapeutic Potential of Spesolimab-Sbzo in the Management of Generalized Pustular Psoriasis Flares in Adults: Evidence to Date.

Generalized pustular psoriasis (GPP) is a rare, chronic, and severe skin disorder characterized by the eruption of non-infectious pustules on an erythematous background often associated with systemic symptoms. It may appear in association with plaque psoriasis or occur in previously healthy individuals. It differs from psoriasis vulgaris in clinical presentation, immunopathogenesis, histology, and therapeutic strategies. Overexpression of interleukin 36 (IL-36) or a loss-of-function mutation of IL-36 receptor antagonist (IL-36RA) are thought to play a pivotal role in the pathogenesis of this disease. There are currently no globally approved guidelines for the treatment of GPP, and the therapies used so far, with variable results, have given unsatisfactory results. Spesolimab, a selective humanized antibody against the IL-36 receptor that blocks its activation, is the first biologic drug approved in Europe in December 2022 for the treatment of GPP flares. It represents a promising therapy, demonstrating efficacy in reducing disease severity and improving patient outcomes. In our review, we have analyzed the latest advancements and findings regarding the efficacy and safety of spesolimab in the context of GPP management.

Efficacy and safety of tildrakizumab in elderly patients: real-world multicenter study (ESTER - study).

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas.Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician's Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores.Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks.Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.

Bimekizumab for the Treatment of Plaque Psoriasis With Involvement of Genitalia: A 16-Week Multicenter Real-World Experience - IL PSO (Italian Landscape Psoriasis).

INTRODUCTION: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. OBJECTIVES: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. METHODS: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician's Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. RESULTS: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g=0) within 16 weeks. Moreover, consistent improvements were observed in PASI scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index (DLQI), signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. CONCLUSIONS: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

Gender perspective in psoriasis: a scoping review and proposal of strategies for improved clinical practice by European dermatologists.

Background: The prevalence of psoriasis is similar between men and women; however, evidence exists of sex- and gender-related differences in disease expression, impact, coping, and needs of patients with psoriasis. These differences are essential and should be considered in clinical practice and research. Objective: To compile available evidence on sex- and gender-related differences in psoriasis, identify the most critical gaps in clinical practice and research, and use it to propose strategies for improved clinical practice. Methods: Six European dermatologists selected the topics to consider according to their relevance in the dermatology setting with the support of methodologists. Evidence on sex- and gender-related differences was obtained by a scoping review based on search strategies in Medline and Cochrane Library from inception to October 2021 using the following terms: arthritis, psoriatic, psoriasis, gender, and sex. The panel discussed the results and proposed strategies by consensus. Results: The scoping review identified broad themes: (1) clinical expression, (2) severity and patient-reported outcomes, (3) psychosocial impact, (4) access to treatments and propensity to treat, (5) comorbidities, and (6) treatment effect. The strategies are based on these broad themes. Limitations: No risk of bias assessment was done due to the scoping nature of the review. Conclusion: This review offers insights into gender differences in psoriasis, providing a foundation for improving clinical practice and patient outcomes.

Effectiveness and safety of bimekizumab for the treatment of plaque psoriasis: a real-life multicenter study-IL PSO (Italian landscape psoriasis).

Introduction: Bimekizumab is a monoclonal antibody that targets Interleukin-17 A and F, approved for the treatment of moderate-to-severe plaque psoriasis. While bimekizumab has been evaluated in several phase-III clinical trials, real-world evidence is still very limited. Method: This multicenter retrospective study included patients affected by plaque psoriasis treated with bimekizumab from May 1, 2022 to April 30, 2023, at 19 Italian referral hospitals. Patients affected by moderate-to-severe plaque psoriasis eligible for systemic treatments were included. The effectiveness of bimekizumab was evaluated in terms of reduction in psoriasis area and severity index (PASI) compared with baseline at weeks 4 and 16. The main outcomes were the percentages of patients achieving an improvement of at least 75% (PASI75), 90% (PASI90) and 100% (PASI100) in PASI score. Results: The study included 237 patients who received at least one injection of bimekizumab. One hundred and seventy-one patients and 114 reached four and 16 weeks of follow-up, respectively. Complete skin clearance was achieved by 43.3% and 75.4% of patients at weeks 4 and 16, respectively. At week 16, 86.8% of patients reported no impact on their quality of life. At week 16, there were no significant differences between bio-naïve and bio-experienced patients in terms of PASI75, PASI90 and PASI100. The most commonly reported adverse events (AEs) were oral candidiasis (10.1%). No severe AEs or AEs leading to discontinuation were observed throughout the study. Conclusion: Our experience supports the effectiveness and tolerability of bimekizumab in a real-world setting with similar results compared with phase-III clinical trials.

Efficacy and Microbiota Modulation Induced by LimpiAL 2.5%, a New Medical Device for the Inverse Psoriasis Treatment.

(1) Inverse psoriasis (IP), also known as intertriginous, typically affects the groin, armpits, navel, intergluteal fissure, and external genitalia. Skin lesions are erythematous plaques of inflammatory nature, smooth, well-delimited, non-scaly, and non-infiltrated. Lesions may be accompanied by itching, pain, or burning sensation. The aim of this study is both to investigate the modulation of the skin microbiota induced by IP and, on the other hand, to test the effectiveness of the new biotechnological product LimpiAL 2.5%. (2) Patients affected by IP were recruited in a private practice and treated for 4 weeks with LimpiAL 2.5% exclusively. The clinical effects on the lesion skin were evaluated, and the skin microbiotas before and after treatment were compared. (3) The clinical outcomes reveled a significant beneficial effect of the tested product. At the same time, LimpiAL increased the biological diversity of the skin microbiota and exerted a significant decrease of some Corynebacterium species, and the increase of some Staphylococcus species. (4) Together, the clinical outcomes and the microbiota analysis suggest that LimpiAL treatment improves the skin condition of affected patients, basically restoring the eubiosis conditions of the affected sites and modulating the bacterial composition of the resident microbiota.

A Real-Life Study on the Use of Tildrakizumab in Psoriatic Patients.

Tildrakizumab is a humanized IgG1κ monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based on the evidence of two randomized and controlled phase-III clinical trials (reSURFACE 1 and reSURFACE 2). Here, we report our real-life experience treating 53 psoriatic patients (19 female and 34 male) who were administered tildrakizumab every 12 weeks and received follow-ups over 52 weeks. Descriptive and inferential statistical analyses were performed, in particular the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and, if applicable, the Nail Psoriasis Severity Index (NAPSI) and Palmoplantar Psoriasis Physician Global Assessment (PPPGA). These were assessed at baseline and after different timepoints (weeks) during the follow-up period. We described and evaluated demographical and epidemiological characteristics in our cohort group, focusing on comorbidities. In this group, 35.9% of patients were female and 64.1% were male, with 47.1% being smokers and with a mean age of 51.2 years. A total of 37.7% of these patients was affected by scalp psoriasis; regarding comorbidities, hypertension was the most frequent (32.5%), followed by psoriatic arthritis (PsA) (18.60%) and diabetes (13.9%). At week 52, 93%, 90.2% and 77% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. In addition, NAPSI, PPPGA and DLQI scores were significantly reduced by week 52. In our cohort of complex psoriasis patients, disease remission began at the end of the fourth week of treatment and remained constant from week 16 to week 52.

Why targeted therapeutics have provided benefit in psoriasis: looking at IL-17 biology.

INTRODUCTION: Psoriasis is an inflammatory, chronic and immune-mediated disease that can affect the skin and joints. Pro-inflammatory cytokines have a dominant role in the pathogenesis of this heterogeneous disease in which the IL-23/IL-17 axis plays a crucial role. The IL-17 family is involved in numerous processes such as immune defense, intestinal disorders and diseases of the central nervous system. In psoriasis, in particular, many cytokines belonging to the IL-17 family are involved in the inflammatory cascade underlying the disease. AREAS COVERED: The knowledge of the mechanisms and pathways behind psoriasis is crucial for the development of new target therapies. We focused on IL-17 biology in order to understand why biological drugs against this cytokine are an effective treatment for moderate to severe psoriasis. Clinical trials results of ixekizumab, brodalumab, secukinumab and bimekizumab have been presented. EXPERT OPINION: Il-17 inhibitors are a very fast and effective treatment against psoriasis; however, fungal infections can occur during their use, due to IL-17 biological functions. Therefore, it should be mandatory to choose the right patients to treat with these monoclonal antibodies in order to have a tailored target therapy for each patient.

Adalimumab Originator vs. Biosimilar in Hidradenitis Suppurativa: A Multicentric Retrospective Study.

This study aimed to compare adalimumab originator vs. biosimilar in HS patients, and to evaluate the effect of a switch to a biosimilar, or a switch back to the originator, in terms of treatment ineffectiveness. Patients with a diagnosis of HS were enrolled from 14 Italian sites. Treatment ineffectiveness was measured using Hurley score. The major analyses were 1) comparison between the two treatment groups (non-switcher analysis), and 2) the cross-over trend of Hurley score between treatment switchers (switcher analysis). Cox and Poisson regression models were used to compare the treatment ineffectiveness between groups. A total of 326 patients were divided into four groups: 171 (52.5%) taking originator; 61 (18.7%) patients taking biosimilar; 66 (20.2%) switchers; 28 (8.6%) switchers from originator to biosimilar and switched. A greater loss of efficacy was observed in the group allocated to the biosimilar than the originator group. The switcher analysis showed an effectiveness loss in the biosimilar compared to the originator. These results seem to indicate that a switch from one drug to the other may lead to a greater risk of inefficacy. A return to the previous treatment also does not ensure efficaciousness.

The Role of Glutathione-S Transferase in Psoriasis and Associated Comorbidities and the Effect of Dimethyl Fumarate in This Pathway.

Psoriasis vulgaris is a chronic inflammatory skin disease characterized by well-demarcated scaly plaques. Oxidative stress plays a crucial role in the psoriasis pathogenesis and is associated with the disease severity. Dimethyl fumarate modulates the activity of the pro-inflammatory transcription factors. This is responsible for the downregulation of inflammatory cytokines and an overall shift from a pro-inflammatory to an anti-inflammatory/regulatory response. Both steps are necessary for the amelioration of psoriatic inflammation, although additional mechanisms have been proposed. Several studies reported a long-term effectiveness and safety of dimethyl fumarate monotherapy in patients with moderate-to-severe psoriasis. Furthermore, psoriasis is a chronic disease often associated to metabolic comorbidities, as obesity, diabetes, and cardiovascular diseases, in which glutathione-S transferase deregulation is present. Glutathione-S transferase is involved in the antioxidant system. An increase of its activity in psoriatic epidermis in comparison with the uninvolved and normal epidermal biopsies has been reported. Dimethyl fumarate depletes glutathione-S transferase by formation of covalently linked conjugates. This review investigates the anti-inflammatory role of dimethyl fumarate in oxidative stress and its effect by reducing oxidative stress. The glutathione-S transferase regulation is helpful in treating psoriasis, with an anti-inflammatory effect on the keratinocytes hyperproliferation, and in modulation of metabolic comorbidities.

Prevalence of Atherosclerosis in Psoriatic Patients Detected with Epiaortic Color Doppler Ultrasound and Computed Tomography Angiography.

INTRODUCTION: Psoriasis (PsO), a chronic inflammatory, multisystemic, and multifactorial disease can cause endothelial dysfunction, artery calcification, and atherosclerotic disease. A higher incidence of vascular occlusive events has been observed in psoriatic patients compared to healthy controls, and multiple studies confirm the association between moderate-severe PsO and atherosclerosis, coronary artery calcification, and higher cardiovascular risk. OBJECTIVE: We sought to analyze atherosclerotic disease prevalence in epiaortic vessels of psoriatic and non-psoriatic patients to understand if PsO could represent an independent risk factor predisposing to atherosclerotic disease. METHODS: We evaluated 47 psoriatic patients without cardiovascular risk factors with color Doppler ultrasound (CDUS). If atheromatous plaques were detected, a computed tomography angiography (CTA) was performed. We evaluated 47 non-psoriatic patients without cardiovascular risk factors with CDUS. Atherosclerosis prevalence in both groups were statistically analyzed. CDUS performance was compared to CTA. RESULTS: In the psoriatic group (mean age 50.9 years), 6 had atheromatous plaques and 12 had an intima-media thickness (IMT) > 1 mm (overall prevalence of atherosclerotic disease: 38.2%). All plaques detected with CDUS were confirmed at CTA. In the control group (mean age 51.3 years), CDUS revealed atheromatous plaques in 4 patients and IMT > 1 mm in 4 ones (overall prevalence of 17%). The difference of atherosclerotic disease prevalence between the groups was statistically significant (P < 0.05). CONCLUSION: Our results highlight that PsO could be considered a predisposing factor for atherosclerotic disease development in epiaortic vessels, as it causes an increased IMT, that is also considered an independent cardiovascular risk factor.

Early predictors of psoriatic arthritis: a Delphi-based consensus from Italian dermatology centers.

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory condition which can affect up to 41% of psoriatic patients [1]. In 40-60% of patients, PsA can determine cartilage destruction and joint deformities, hereby heavily impacting physical function and quality of life, even increasing the risk of death compared to the general population [1]. PsA manifestations usually develop after psoriasis onset; therefore, dermatologists play a crucial role in the detection of early signs of arthritis. In our study, we aimed to identify simply detectable clinical and ecographic signs of early PsA and to assess their reliability. METHODS: We assessed the opinion of a group of expert dermatologists, who were asked to express their opinion on the level of association between the selected anamnestic, clinical or instrumental signs and the onset of psoriatic arthritis by giving a score to each item. RESULTS: Psoriatic onycopathy, signs of dactylitis and ultrasonographic alterations of selected joints were, respectively, the dermatologic, rheumatologic and imaging signs which had the strongest significance in the opinion of the experts. CONCLUSIONS: These signs should be carefully looked for during dermatological examinations in order to detect early PsA.

Recurrent Aphthous Stomatitis: Treatment and Management.

BACKGROUND: Recurrent aphthous stomatitis consists of the presence of abrasions or ulcerations located on mucosae (oral or genital). OBJECTIVES: The aim of this article is to review the current literature providing the main causes related to recurrent aphthous stomatitis and insights into treatment and management of this clinical condition. METHODS: Articles matching terms that correlated with "recurrent aphthous stomatitis" were searched on PubMed, EMBASE, and Cochrane Library and selected according to their pertinence. RESULTS: Several forms of aphthous stomatitis have been described, based on the extent (minor, major), morphology (herpetiform) and associations to other signs (Behçet syndrome or more complex inflammatory syndromes). Topical as well as systemic treatments have been described to obtain a faster remission of the aphthosis or to reduce associated symptoms such as pain. CONCLUSIONS: Recurrent aphthous stomatitis can have a mild-to-severe clinical appearance, being mainly localized on the oral mucosa or at the level of the genital area. Different strategies have been described so far for its management and treatment.

Beyond-Mild Psoriasis: A Consensus Statement on Calcipotriol and Betamethasone Dipropionate Foam for the Topical Treatment of Adult Patients.

INTRODUCTION: There are clear treatment options for mild psoriasis where topical therapies are the mainstay, and for severe psoriasis where systemic therapy (biologic or non-biologic) is necessary. However, there is less clarity in the 'grey zone' of patients in the moderate or so-called 'beyond-mild' segment. There are frequent delays to the initiation, discontinuation, switching and dose change in treatment, and many patients fail to continue treatment because of concerns about safety or lack of efficacy. Treatment with topical therapies, such as calcipotriol and betamethasone dipropionate (Cal/BD) combinations, may be suitable for these patients. METHOD: These consensus recommendations on the use of topical therapies including Cal/BD foam for beyond-mild psoriasis originated from a modified Delphi process of European clinical experts. In the process, the experts iteratively refined a series of draft statements, which had to receive ≥ 80% approval to be incorporated into the consensus. RESULTS: The experts identified three main themes: Cal/BD foam as monotherapy, as an add-on to non-biologic systemic therapies and as an add-on to systemic biologics. The consensus emphasises disease factors and patient preference in treatment choice, summarises the evidence base for Cal/BD foam monotherapy for flare treatment as well as long-term management, and identifies the potential for improved treatment outcomes, such as reduced time to onset of action and reduced systemic dose to minimise side effects for add-on Cal/BD therapy to non-biologic systemics. The recommendations regarding add-on Cal/BD foam to biologics are similar to those for non-biologic systemic therapies, but also include suggestions for patients on biologics who are late responders. As clinical choices of Cal/BD combination vary, we have here often used 'Cal/BD' without reference to any particular formulation. CONCLUSIONS: These recommendations aim to give practical guidance to those treating patients with beyond-mild psoriasis, to support patients' use of topical preparations and to optimise treatment outcomes.