Multi-failure psoriasis patients: characterization of the patients and response to biological therapy in a multicenter Italian cohort.

INTRODUCTION: Patients with psoriasis who have failed multiple biologic drugs have been defined as "multi-failure," although there are no clear data on the characteristics, comorbidities, and best treatment strategies for this population. Nowadays, given the next generation and the number of biologics available, patients are considered multi-failure when ≥4 biologics fail to achieve a good response. METHODS: Demographic characteristics and efficacy of anti-interleukin drugs in multi-failure patients were compared to a cohort of general psoriatic patients treated with IL-23 or IL-17 inhibitors. RESULTS: In total 97 multi-failure patients (≥4 lines of biologics) were compared with 1,057 patients in the general cohort. The current drugs in the multi-failure group were risankizumab (34), ixekizumab (23), guselkumab (21), brodalumab (7), tildrakizumab (5), ustekinumab (4), secukinumab (2), and certolizumab pegol (1). A significant difference was found in the multi-failure cohort for age of psoriasis onset (mean 29.7 vs. 35.1, P < 0.001), concurrent psoriatic arthritis (45.4 vs. 26.9%, P < 0.001), diabetes mellitus (30.9 vs. 10.9%, P < 0.001), and cardiovascular comorbidity (54.6 vs. 39.8%, P = 0.005). In multi-failure patients, current biological therapy showed a good initial response (PASI 90 and 100 of 41.24 and 27.84%, respectively, at 16 weeks); the response tended to decline after 40 weeks. Anti-IL-17 agents showed clinical superiority over IL-23 agents in terms of achieving PASI90 at 28 weeks (P < 0.001) and 40 weeks (P = 0.007), after which they reached a plateau. In contrast, IL-23 agents showed a slower but progressive improvement that was maintained for up to 52 weeks. A similar trend was also seen for PASI100 (28 weeks P = 0.032; 40 weeks P = 0.121). CONCLUSIONS: The multi-failure patient is characterized by many comorbidities and longstanding inflammatory disease that frequently precedes the introduction of systemic biologic therapy. Further studies are needed to identify more specific criteria that could be applied as a guideline by clinicians.

Effectiveness and Safety of Deucravacitinib for the Management of Psoriasis: A Review of the Current Literature.

Psoriasis management may be challenging, particularly for moderate-to-severe forms of the disease. Indeed, conventional systemic treatments are often avoided for contraindications or the risk of adverse events as well as phototherapy is often limited by logistic concerns. Despite the development of biological drugs and small molecules revolutionized the treatment options showing promising results in terms of safety and effectiveness, some limitations remain. Thus, there is still a need for new therapies that are always welcome in order to tailor the treatment to the patient and to have a higher level of performance, especially in order to maintain long-term effectiveness. In this scenario, deucravacitinib, an oral small molecule which selectively inhibits Tyrosine Kinase 2, may represent a promising weapon in psoriasis management. The aim of our manuscript is to review the current knowledge on the efficacy and safety of deucravacitinib for the management of psoriasis.

The holistic approach to psoriasis patients with comorbidities: the role of investigational drugs.

INTRODUCTION: Psoriasis is a high-burden syndrome characterized by cutaneous and extracutaneous manifestations that profoundly reduce patients' quality of life. The presence of concomitant comorbidities often represents a limit to the most appropriate psoriasis treatment that will be overcome by the development of drugs effective for diseases with common pathogenetic pathways. AREAS COVERED: The current review summarizes the latest findings on investigational drugs for psoriasis and their role on potentially concomitant diseases that share similar pathogenetic pathways. EXPERT OPINION: The development of novel drugs that target key-molecules in the pathogenesis of several diseases, including psoriasis, will impact on the reduction of polypharmacy and drug interaction with increased patients' compliance to treatment, wellbeing, and quality of life. Certainly, the efficacy and safety profile of each novel agent must be defined and evaluated in real-life since the performance may vary according to comorbidities and their severity. Anyway, future is now, and research must continue in this direction.

Anti-IL23 biologic therapies in the treatment of psoriasis: real-world experience versus clinical trials data.

Nowadays, the biological equipment available for the treatment of moderate-to-severe psoriasis is plenty. Anti-interleukin-23 represents the latest class of biologic approved for the management of moderate-to-severe psoriasis. Their efficacy and safety have been assessed through two major sources: clinical trials (CTs) and real-world experiences data (RWE). Notably, the two sources differ from one another, but together, they complement information and current knowledge on both efficacy and safety of biological therapy. We carry out a review on CTs and RWE reports on the latest group of biological approved for moderate-to-severe psoriasis: anti-IL23 (guselkumab, risankizumab, and tildrakizumab).

Towards Personalized Medicine in Psoriasis: Current Progress.

Although innovative targeted therapies have positively revolutionized psoriasis treatment shifting treatment goals to complete or almost complete skin clearance, primary or secondary lack of efficacy is still possible. Hence, identifying robust biomarkers that reflect the various clinical psoriasis phenotypes would allow stratify patients in subgroups or endotypes, and tailor treatments according to the characteristics of each individual (precision medicine). To sum up the current progress in personalized medicine for psoriasis, we performed a review on the available evidence on biomarkers predictive of response to psoriasis treatments, with focus on phototherapy and systemic agents. Relevant literature published in English was searched for using the following databases from the last five years up to March 20, 2022: PubMed, Embase, Google Scholar, EBSCO, MEDLINE, and the Cochrane library. Currently, more evidence exists towards biologicals, as justified by the huge health care costs as compared to phototherapy or conventional systemic drugs. Among them, most of the studies focused on anti-TNF and IL12/23, with still few on IL17 (mainly secukinumab). The most discussed biomarker gene is the HLA-C*02:06 status that has been shown to be associated with psoriasis, and also differential response to biologicals. Although its positivity is associated with great response to MTX, debatable results were retrieved concerning both anti-TNF and IL12/23 while it seems not to affect secukinumab response. Personalized treatment in psoriasis would provide excellent outcome minimizing the risk of side effects. To date, although several candidates were proposed and assessed, the scarcity and heterogeneity of the results do not allow the identification of the gold-standard biomarker per each treatment. Anyway, the creation of a more comprehensive panel would be more reliable for the treatment decision process.

Long-term proactive management of psoriasis with calcipotriol and betamethasone dipropionate foam: an Italian consensus through a combined nominal group technique and Delphi approach.

BACKGROUND: Although long-term management of psoriasis is paramount, this approach is challenging in clinical practice. In the recent PSO-LONG trial, a fixed-dose combination of betamethasone dipropionate (BD) and calcipotriol (Cal) foam applied twice a week on non-consecutive days for 52 weeks (proactive treatment) reduced the risk of relapse. However, the role of Cal/BD foam in the long-term management of psoriasis needs further clarifications. The ProActive Management (PAM) program, a nationwide Italian project, aims at reaching a consensus on the role of proactive management of psoriasis. METHODS: A steering committee generated some statements through the nominal group technique (NGT). The statements were voted by an expert panel in an adapted Delphi voting process. RESULTS: Eighteen statements were proposed, and the majority of them (14/18) reached a consensus during the Delphi voting. The need to provide long-term proactive topical treatment to reduce the risk of relapse for the treatment of challenging diseases sites or in patients where phototherapy or systemic therapies are contraindicated/ineffective was widely recognized. A consensus was reached about the possibility to associate the proactive treatment with systemic and biological therapies, without the need for dose intensification, thus favoring a prolonged remission. Moreover, the proactive treatment was recognized as more effective than weekend therapy in increasing time free from relapses. Approaches to improve adherence, on the other hand, need further investigation. CONCLUSIONS: The inclusion in guidelines of a proactive strategy among the effective treatment options will be a fundamental step in the evolution of a mild-moderate psoriasis therapeutic approach.

Assessment of the efficacy, skin acceptability and cosmetic quality of an adjuvant cream based on 40% urea and amino-inositol in the treatment of mild psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease with a multifactorial genesis. Structural changes are encountered in psoriasis and skin barrier function is impaired. Tight junctions (TJs) play a key role in skin barrier dysfunction. Loss of profilaggrin or filaggrin leads to changes in the stratum corneum and consequent loss of water and the development of xerosis. METHODS: We carried out an observational study to evaluate the efficacy, skin acceptability and cosmetic qualities of a cream formulation, based on 40% urea and amino-inositol, in the treatment of mild psoriasis in the absence of other associated cosmetic/pharmacological treatments. All parameters were evaluated before (T0) and after 4 weeks (T4). Efficacy assessment was based on both clinical evaluation and photographic documentation. RESULTS: The results showed significant clinical improvement (-64.18% PASI, -57.11% BSA, -61.84% Plaque Score, -41.86% PGA and -76.34% VAS -77.5 DLQI) in 4 weeks of treatment. No significant side effects were reported. Similarly, the degree of satisfaction with the product and adherence to its use were particularly satisfactory among patients. CONCLUSIONS: The tested product was found to be a promising, effective adjuvant treatment in patients with mild psoriasis, and was also useful in reducing itchy symptoms, the impact on quality of life, as well as significantly reducing the clinical signs of psoriasis.

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. METHODS: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). RESULTS: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time. CONCLUSION: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Psoriasis awareness among general population: preliminary results of an online survey.

BACKGROUND: Psoriasis represents one of the most common skin diseases in Italy, with a prevalence of 2.9%. It has been defined as a noncommunicable disease, due to its high burden and impact on patients' quality of life. The aim of our observational study was to assess the actual knowledge and perception of psoriasis in Italian population by administering an online 10-question survey to a representative sample general population. METHODS: An online 10-question survey was administered to a representative sample general population from September 2019 to December 2019. A representative sample of general population (age ≥18 years) was enrolled by promoting the online survey through multiple means of communication such as social sites (Facebook, Instagram) or delivering a questionnaire link in public spaces (outpatient clinic, pharmacy). All results were then collected and analyzed in graphs by the Google form platform. RESULTS: One hundred fifty-one individuals participated in the survey. Results showed that 7.3% (N.=11) of general population were not familiar with the term psoriasis; 4.6% (N.=7) thought to psoriasis as an infectious disease and 6% (N.=9) thought that psoriasis was contagious. Interestingly, 39.1% (N.=59) of participants have never heard about targeted/biologic therapy. Our study is limited by the small sample size as well as lack of data regarding sex, age and education level of the study participant. CONCLUSIONS: There is still lack of knowledge of psoriasis among general population, representing an obstacle for patients' everyday activities and quality of life. Future studies to investigate the details of this impaired knowledge and new psoriasis campaign on large scale should fill this gap are required.

Ultraviolet radiation, vitamin D, and COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become pandemic on March 11th, 2020. COVID-19 has a range of symptoms that includes fever, fatigue, dry cough, aches, and labored breathing to acute respiratory distress and possibly death. Health systems and hospitals have been completely rearranged since March 2020 in order to limit the high rate of virus spreading. Hence, a great debate on deferrable visits and treatments including phototherapy for skin diseases is developing. In particular, as regards phototherapy very few data are currently available regarding the chance to continue it, even if it may be a useful resource for treating numerous dermatological patients. However, phototherapy has an immunosuppressive action possibly facilitating virus infection. In the context of COVID-19 infection risk it is important to pointed out whether sunlight, phototherapy and in particular ultraviolet radiation (UV-R) constitute or not a risk for patients. In this review we aimed to focus on the relationship between UV-R, sunlight, phototherapy, and viral infections particularly focusing on COVID-19.

Erythrodermic pityriasis rubra pilaris treatment: Two case reports and literature review.

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis characterized by hyperkeratotic follicular papules and erythematous-desquamative plaques that tend to progressively evolve into erythroderma. Treatment is challenging given that international guidelines are not available and large-scale trials do not exist. Traditionally, many topical and systemic drugs had been used as consolidated agents; recently, biologicals are gaining increasing importance, promisingly dominating the therapeutic scenario ahead. Herein, we present a case series showing the "past" and the "future" therapeutic approaches to erythrodermic PRP, one case treated with acitretin and nb-UVB phototherapy combination, while the other with ustekinumab, performing also a throughout literature review.

Vitamin D and psoriasis: an update for dermatologists and nutritionists.

Psoriasis is a common chronic immune-mediated inflammatory skin disease, now considered a systemic inflammatory process with several comorbidities. The skin produces vitamin D by the action of ultraviolet light. Vitamin D performs various immunomodulatory, anti-inflammatory, antioxidant and antifibrotic actions. The immunomodulatory effects of vitamin D offer opportunities to improve the treatment of several autoimmune diseases, such as psoriasis. In the literature, several significant associations are reported between low levels of vitamin D and psoriasis. Today, topical vitamin D represents an important therapeutic option due to its action on the proliferation and maturation of keratinocytes. The situation is different regarding the oral intake and integration of vitamin D in psoriasis patients. The use of vitamin D supplementation as an adjunctive treatment option in these patients is still discussed. This work aims to analyze the association between psoriasis and vitamin D levels according to dermatologists and nutritionists.

Hailey-Hailey disease successfully treated with vitamin D oral supplementation.

Hailey-Hailey disease (HHD) also known as familial benign chronic pemphigus is a rare autosomal dominant genodermatosis. HHD treatment is often not satisfactory and hence, various modalities of treatment have been tried. We describe the case of a 37-year-old woman with a 2 years history of macerated erythematous plaques along with erosions, fissures, and crusts located on axillae and submammary areas, successfully treated with only oral supplementation of vitamin D (800 I.U./die) for 3 months. We reported this case to suggest that oral vitamin D may be enumerated in the various treatments proposed for HHD so far due to its rapid efficacy on skin lesions and symptoms.

Coffee consumption, metabolic syndrome and clinical severity of psoriasis: good or bad stuff?

Despite the wide consumption of coffee, its anti-inflammatory effect on clinical severity of psoriasis is still debatable. The aim of this study was to evaluate the association between the coffee consumption and clinical severity of psoriasis in a sample of patients stratified according to the presence of the metabolic syndrome (MetS) and smoking. This cross-sectional case-control observational study was conducted on 221 treatment-naïve psoriatic patients. Lifestyle habits, anthropometric measures, clinical and biochemical evaluations were obtained. Clinical severity of psoriasis was assessed by Psoriasis Area and Severity Index (PASI) score. Data on energy caloric intake and coffee consumption were collected using a 7-day food diary record. The coffee consumption was analyzed as coffee intake (consumers and non-consumers) and daily servings (range 0-4 servings/day). Coffee consumers have a lower PASI score vs non-consumers (p < 0.001). The lowest PASI score and MetS prevalence were found in patients consuming 3 cups of coffee/day (p < 0.001), which was also the most common daily serving (34.8%), whereas the highest PASI score was found among those drinking ≥ 4 cups/day. Grouping the case patients according to smoking and MetS, the best odds of PASI score was observed in those drinking 3 cups of coffee per day and no smokers, after adjusting for total energy intake (OR 74.8; p < 0.001). As a novel finding, we reported a negative association between coffee intake, MetS prevalence and clinical severity of psoriasis. The evaluation of the anti-inflammatory effect of coffee on clinical severity of psoriasis, whose metabolic risk increases along with its clinical severity, could be of great importance from a public health perspective.

Vitamin D and its role in psoriasis: An overview of the dermatologist and nutritionist.

Psoriasis is a chronic immune-mediated inflammatory skin disease. Psoriasis lesions are characterized by hyper-proliferation of epidermal keratinocytes associated with inflammatory cellular infiltrate in both dermis and epidermis. The epidermis is the natural source of vitamin D synthesis by sunlight action. Recently, a role for vitamin D in the pathogenesis of different skin diseases, including psoriasis, has been reported. Indeed, significant associations between low vitamin D status and psoriasis have been systematically observed. Due to its role in proliferation and maturation of keratinocytes, vitamin D has become an important local therapeutic option in the treatment of psoriasis. To date, the successful treatment based on adequate dietary intake of vitamin D or oral vitamin D supplementation in psoriasis represent an unmet clinical need and the evidence of its beneficial effects remains still controversial. This information is important either for Dermatologists and Nutritionists to increases the knowledge on the possible bi-directional relationships between low vitamin D status and psoriasis and on the potential usefulness of vitamin D in psoriasis with the aim not only to reduce its clinical severity, but also for delineating the risk profile for co-morbidities cardiac risk factors that may result from psoriasis. In the current review, we analyzed the possible bi-directional links between psoriatic disease and vitamin D.