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

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.

Oral Diseases During Systemic Psoriatic Drugs: A Review of the Literature and Case Series.

INTRODUCTION: The oral health of psoriatic patients seems to be compromised compared to that of control individuals: many published studies have investigated the relationship between psoriatic disease and gingivitis, periodontitis, and missing teeth. However, data from these studies are not consistent nor exhaustive. Moreover, no study has considered the possible specific effects of conventional and biological systemic psoriatic treatments. OBJECTIVE: We report a narrative review of the literature about the possible link between anti-psoriatic drugs and oral disease onset and present case series of patients that have experienced oral disease during systemic therapy for psoriasis. METHODS: This is a narrative review. The literature search was performed using the MEDLINE database. From the selected articles, additional references were identified by a manual search among the cited literature. RESULTS: Oral adverse events during psoriatic therapies can be found in sporadic cases. The specific mechanisms of interplay between oral anatomic structures and the pathway targeted by the systemic agents will be investigated in depth. CONCLUSION: All psoriatic patients who are candidates for conventional or biological systemic therapy should have regular oral health check-ups with a dentist and a dermatologist to prevent oral complications. Dermatologists and oral medicine specialists should be ready to recognize and manage this increasing number of oral adverse drug reactions during systemic treatments for psoriatic disease so as to provide patients with sufficient information about this risk and to stress the fundamental importance of regular dental assessments and good oral hygiene.

Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris.

Introduction: The involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms. Methods: We performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions. Results: The results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses. Conclusions: These data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases.

Oral Lesions and Oral Health-Related Quality of Life in Adult Patients with Psoriasis: A Retrospective Chart Review.

Psoriasis is a widespread chronic inflammatory skin disease, that negatively affects physical and emotional well-being and quality of life, as shown by the generally low Dermatology Life Quality Index (DLQI). Psoriasis is burdened by associated comorbidities and some patients manifest concurrent oral lesions, although the existence of oral psoriasis remains controversial. Psoriasis-specific and nonspecific oral lesions and Oral Health-Related Quality of Life (OHRQoL), self-assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire, were retrospectively reviewed in adult untreated psoriasis patients with ≥15 teeth, who were non-smokers and had no dental or periodontal infections. Sample (age, gender, comorbidities) and descriptive variables (Body Surface Area-BSA, Psoriasis Area and Severity Index-PASI, Dermatology Life Quality Index-DLQI, severity of psoriasis, distribution of lesions and predominant involvement, years since diagnosis) were correlated with DLQI and OHIP-14 and compared by baseline DLQI and OHRQoL classes. Charts from 90 participants were included. No oral lesions were detected, and excellent/good OHRQoL was found in 94% of the participants. DLQI scores displayed positive significant associations with PASI and BSA, while OHIP-14 with hypertension and IMID, and age. PASI and BSA were significantly higher in participants with DLQI > 10 and also differed significantly among OHQRoL ranks, as well as mucosal involvement and comorbidities. Specifically, among subjects revealing an Excellent OHQRoL, 92.6% were non-IMID, 75% non-hypertensive, 89.7% non-diabetic subjects, 86.8% of non CVD-subjects.

Dupilumab therapy reduces urinary biopyrrin levels in atopic patients: a new possible biomarker of oxidative status in atopic dermatitis.

BACKGROUND: Accumulating evidence suggests that oxidative stress is involved in the inflammatory process of atopic dermatitis (AD). Biopyrrins are the end products of the oxidative reaction of bilirubin with reactive oxygen species. The aim of our study was to explore the correlation between urinary biopyrrin levels and AD severity as well as to assess the possible modification of them in AD patients during biologic therapy with human monoclonal antibody dupilumab. METHODS: For this purpose, 25 adult patients with moderate-severe AD who were candidates for dupilumab therapy independently from the study, and 15 healthy control subjects, matched by sex and age, were enrolled. Morning urine samples were collected from all study participants. For AD patients, a collection was planned before starting therapy with dupilumab (WO), after 8, 16, 52 weeks (W8, W16, W52, respectively), and two years (Y2) of treatment. The analysis of urinary levels of biopyrrins was performed by ELISA assay. RESULTS: Our results demonstrated that urinary biopyrrin levels were significantly augmented in AD patients, and interestingly they correlated with disease severity. Furthermore, dupilumab therapy decreased levels of urinary biopyrrins in AD patients after eight and 16 weeks, maintaining the result after 52 weeks as well as after two years of treatment. The correlation analysis showed a statistically significant positive correlation between the urinary concentration of biopyrrins and EASI Index, circulating total IgE as well as plasma C reactive protein levels. CONCLUSIONS: Dupilumab therapy was able to ameliorate oxidative state in AD patients.

Efficacy, tolerability and patient's satisfaction for the treatment of moderate to severe plaque psoriasis with apremilast in the real-life setting of Campania region, Italy.

BACKGROUND: Little information is available from real-life studies evaluating the efficacy of apremilast in moderate-to-severe psoriasis. METHODS: In this real-life study, we retrospectively examined a database of 231 patients with moderate-to-severe psoriasis treated with apremilast (30 mg twice/day) and followed up for 52 weeks. Disease severity and treatment response were assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 16, 24, and 52 weeks. Quality of life was assessed by the Dermatology Life Quality Index (DLQI). RESULTS: PASI score decreased from 14.6 at baseline to 4.1 and 1.2 at 16 and 24 weeks. At 24 weeks, 86.7% of patients achieved a PASI score of ≤3 and this improved up to 52 weeks, where all patients had a PASI score of ≤3. At 24 weeks, PASI 75, 90 and 100 responses were achieved in 92%, 83.2% and 36.3% of patients, respectively. At 52 weeks, PASI 75, 90 and 100 response were achieved in 97%, 89.3% and 62% of patients, respectively. DLQI score was 12.4 at baseline and decreased to 2 at week 24, and close to 0 at week 52. No serious adverse event was reported during the treatment with apremilast. CONCLUSIONS: In patients with moderate-severe chronic psoriasis in a real world-setting apremilast was shown to be effective and safe up to 52 weeks.

Brodalumab for the Treatment of Moderate-to-Severe Psoriasis: An Expert Delphi Consensus Statement.

Brodalumab is a recombinant, fully human immunoglobulin IgG2 monoclonal antibody specifically targeted against interleukin-17RA that has been approved for the treatment of moderate-to-severe psoriasis in Europe. We developed a Delphi consensus document focused on brodalumab for the treatment of moderate-to-severe psoriasis. Based on published literature and their clinical experience a steering committee drafted 17 statements covering 7 domains specific to the treatment of moderate-to-severe psoriasis with brodalumab. A panel of 32 Italian dermatologists indicated their level of agreement using a 5-point Likert scale (from 1 = "strongly disagree" to 5 = "strongly agree") using an online modified Delphi method. After the first round of voting (32 participants), positive consensus was reached for 15/17 (88.2%) of the proposed statements. Following a face-to-face virtual meeting, the steering committee decided that 5 statements would form "main principles" and 10 statements formed the final list. After a second round of voting, consensus was reached in 4/5 (80%) of the main principles and 8/10 (80%) for consensus statements. The final list of 5 main principles and 10 consensus statements identify key indications specific to the use of brodalumab in the treatment of moderate-to-severe psoriasis in Italy. These statements aid dermatologists in the management of patients with moderate-to-severe psoriasis.

Understanding Barriers Impacting upon Patient Wellbeing: A Nationwide Italian Survey and Expert Opinion of Dermatologists Treating Patients with Moderate-to-Severe Psoriasis.

A nationwide cross-sectional online survey was administered to dermatologists managing patients with moderate-to-severe plaque psoriasis across Italy to obtain real-world dermatologists' perspectives on the impact of psoriasis and its treatment on patients' daily lives and quality of life (QoL). A total of 91 dermatologists (aged 39.1 ± 11.2 years) completed a 31-question survey and workshop sessions were undertaken in order to identify the best management approach to achieve patient wellbeing. Social (4.2 ± 0.1), physical (4.26 ± 0.2) and mental components (4.1 ± 0.3) were rated by dermatologists as contributing to patient wellbeing to similar extents. While a high proportion (85.4%; rating of 4.3 out of 5) of dermatologists felt that they considered the QoL of patients, a lower proportion (69.6%; rating of 3.7 out of 5) felt that patients were satisfied in this regard. The psoriasis area and severity index and body surface area were the instruments most frequently used to assess the physical domain, while interviews/questions and the dermatology life quality index were used to assess social and mental domains, with only 60% of dermatologists following up on these aspects. The importance of investigating the presence of comorbidities was recognized but not always carried out by many dermatologists, (>70%), particularly for obesity and anxiety/depression. This survey identified key components contributing to barriers impacting on the QoL of patients with moderate-to-severe psoriasis from the perspective of the dermatologist.

Oxidative Stress in Atopic Dermatitis and Possible Biomarkers: Present and Future.

Oxidative stress is important in the pathogenesis of atopic dermatitis (AD); it can damage keratinocytes, increase dermal inflammation, and reduce skin barrier function, the hallmarks of atopic dermatitis pathogenesis. Measuring oxidative stress is possible by identifying peripheral markers, which could have a predictive value of disease severity, disease progression and response to therapy, with a potentially significant impact on patient management. Our review explored this fascinating field of research, focusing on old and new possible biomarkers that may represent an effective tool to investigate the inflammatory-oxidative axis in AD, adding clinically important information to patient care.

Immuno-Pathogenesis of Chronic Inflammatory Skin Diseases: Novel Molecular Targets and Biomarkers.

Chronic inflammation has a crucial pathogenetic role in many diseases, including cutaneous chronic inflammatory disorders, such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and chronic urticaria [...].

Prevalence, Features and Degree of Association of Oral Lesions in COVID-19: A Systematic Review of Systematic Reviews.

Regardless of rapidly emerging findings on oral lesions described in adult SARS-CoV-2-positive subjects, the evidence level remains quite low and rather contrasting; therefore, the present systematic review of systematic reviews primarily aims to point out the overall prevalence of diagnosed cases. Secondary aims are to estimate the degree of association between oral lesions and SARS-CoV-2 infection and to grade, based on the reported frequency, the primary oral lesions, with related clinical presentations and microscopic features, in relation to COVID-19 forms. A study protocol compliant with the PRISMA statement was developed. Twelve studies were included, reporting highly heterogeneous and incomplete findings, thus precluding a meta-analysis. Further studies should be conducted to assess the overall prevalence of cases diagnosed with oral lesions among adult SARS-CoV-2-positive subjects, especially considering novel viral variants, and to determine their degree of association with SARS-CoV-2 infection and COVID-19 forms. Moreover, the reported findings noticed the need to evaluate the putative role both of SARS-CoV-2 in oral lesions genesis and of periodontitis and periodontal microbiome in COVID-19 worsening and re-activations. Deeper insights into oral lesions in adult SARS-CoV-2-positive subjects could enhance the comprehension of illness pathogenesis, natural history and clinical presentation, thus improving the preparedness of health professionals in the inter-disciplinary management of COVID-19.

Sharing Patient and Clinician Experiences of Moderate-to-Severe Psoriasis: A Nationwide Italian Survey and Expert Opinion to Explore Barriers Impacting upon Patient Wellbeing.

A nationwide survey was conducted in adult patients with psoriasis (PsO) across Italy to obtain their real-world perspective of the impact of PsO on their wellbeing. Patients completed a 26-question survey (based on the patient benefit index; PBI, The Dermatology Life Quality Index; DLQI and the World Health Organization-five; WHO-5 wellbeing index) and workshop discussion sessions were undertaken by dermatologists to interpret results from the survey. 392 patients with PsO completed the survey. Analysis of results was restricted to patients who had moderate-to-severe plaque psoriasis (assessed by patients; n = 252; 64.3%). Dermatologists (n = 32) completed one question from the survey related to wellbeing and rated social, physical and mental domains as contributing to a similar extent, with comparable scores also observed by patients. For treatment, biologics yielded higher scores on average, whereas little difference was observed between topical and conventional systemic treatments. Only 23.8% of patients felt that their dermatologist was taking into consideration their wellbeing and 32.6% of the patients considered their therapy as inadequate in improving signs and symptoms of the disease. This survey identified key factors contributing to barriers impacting on patient wellbeing. Simple, but comprehensive questionnaires can provide important insight to patients' needs that may significantly increase clinician awareness during visits leading to tailored treatment.

Lack of reactivation of tuberculosis in patients with psoriasis treated with secukinumab in a real-world setting of latent tuberculosis infection.

BACKGROUND: Some biologics for psoriasis, especially anti-tumor necrosis factor (TNF)-α therapies, may re-activate latent tuberculosis (TBC) infection with consequent morbidity and mortality. However, there is a low reported incidence of conversion to positive TBC status among patients with psoriasis treated with second-generation biologic therapies, particularly anti-interleukin (IL)-17 therapies such as secukinumab. OBJECTIVES: To evaluate the safety profile of secukinumab in psoriasis patients with latent TBC infection. METHODS: Real-life data were collected by retrospective chart review on patients with moderate-to-severe psoriasis who showed positivity for TBC screening at baseline and underwent secukinumab treatment for psoriasis at six Italian centers. Patients received secukinumab 300 mg at week 0/1/2/3/4, then every 4 weeks. RESULTS: Fifty-nine patients were enrolled; 30.5% also had psoriatic arthritis and other comorbidities were common. At baseline, the mean psoriasis duration was 14.5 years. Ten (17%) patients did not undergo prophylaxis before starting secukinumab. Conversely, isoniazid ± rifampicin or rifampicin alone prophylaxis was administered in 49/59 (83.1%) patients. After a mean treatment duration of 84 weeks, there were no cases of TBC reactivation and no unexpected safety signals. CONCLUSIONS: Secukinumab use over an extended period was safe in psoriasis patients with latent TBC, even in patients who did not receive chemoprophylaxis.

Assessing the Beneficial Impact of a Patient Support Program in Secukinumab-Treated Patients with Psoriasis in Italy.

PURPOSE: For patients with psoriasis, treatment adherence and persistence are fundamental if therapeutic goals are to be met. Patient Support Programs (PSPs) may be used as a support tool to assist patients and health care professionals optimize treatment and improve disease management. PATIENTS AND METHODS: In Italy, the PSP PSOLife CARE, which began on the 9th of February 2017 and is ongoing, aimed to support patients with psoriasis under therapy with secukinumab (Cosentyx®). A team of medical professionals including Dermatologists, Psychologists, Nutritionists, and field Nurses provided outpatient treatment as well as remote support via phone calls. Patients had a standard duration in the Program of 6 months. This report analyzes the data of patients who benefited from the Program from February 2017 to August 2020, for a total observation of 42 months. RESULTS: We provide here a descriptive report on the benefits of participation in the PSOLife CARE Program for patients with psoriasis and medical professionals involved in their care. Throughout their time in the PSOLife CARE Program, patient satisfaction remained consistently high with sustained improvements observed in all aspects of quality of life (ie emotional, social, physical, and economic). Despite exiting from the Program, most patients continued to adhere to secukinumab. Medical professionals also reported positive outcomes on their interactions with patients, with more than half of those surveyed rating the overall quality of the Program as "Outstanding". CONCLUSION: By supporting treatment adherence, the PSOLife CARE Program may have empowered patients to better manage their psoriasis, increasing their satisfaction with treatment and quality of life.

Clinical predictors of psoriatic arthritis and osteoclast differentiation.

Psoriasis and psoriatic arthritis (PsA) are interrelated inflammatory diseases. Psoriasis usually precedes PsA onset and represents a well-established risk factor for PsA development. Bone erosion is a hallmark of PsA, and the contribution of cutaneous psoriatic inflammation in this process has been demonstrated. However, little is still known on the pathogenetic mechanisms that link psoriatic skin to joint damage. Clinical features of psoriatic disease, including specific body site involvement, seem to be important risk predictors of PsA. The aim of this pilot research study was to investigate if psoriatic cutaneous inflammation, affecting these anatomical predictive sites for PsA, could be linked to osteoclast differentiation and activity. Our results showed that psoriasis skin localizations were positively related to the osteoclastogenic profile in psoriatic patients. These results provide new insights into the fascinating skin-joint axis concept.

Atopic Dermatitis: Epidemiology and Clinical Phenotypes.

Atopic dermatitis (AD) is a chronic, lifelong, relapsing condition. The wide spectrum of the possible clinical presentations, depending on patient' s age, age of onset of disease, topography and morphology of dermatitis, limits the epidemiologic information on its prevalence and incidence. A clear definition of the different clinical AD phenotypes and epidemiology is essential for an appropriate patient's treatment and management, in particular for adults. This review summarizes the most recent epidemiologic data from the 21st century, on AD prevalence and incidence rates either in children or adults, with a special focus on their trends in Europe. Moreover, an effort to categorize diverse AD clinical expressions, has been made, aiming to facilitate differential diagnosis and speed up the start of the correct therapy.