Effectiveness of Ixekizumab in Elderly Patients for the Treatment of Moderate-to-Severe Psoriasis: Results From a Multicenter, Retrospective Real-Life Study in the Lazio Region.

INTRODUCTION: This was an observational, retrospective, multicenter study, enrolling elderly patients (>65 years old) treated with ixekizumab with a diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) during the period 2020 to 2023. OBJECTIVES: Efficacy of ixekizumab in elderly patients in the treatment of moderate to severe psoriasis. METHODS: We included 73 patients with psoriasis (32.9%), psoriatic arthritis (1.4%) and both of them (PsO-PsA 65.8%), attending the outpatient clinics of seven Italian referral center for psoriasis in Lazio region: Policlinico Umberto I Università Roma La Sapienza, Sant'Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Biomedico Roma, Istituto Dermopatico dell'Immacolata - IDI and Policlinico Tor Vergata. We collected data related to the characteristics of the patients (age, sex, body mass index) and of the disease (age at onset, duration of psoriasis, previous treatments). The severity of psoriasis was measured with the Psoriasis Area and Severity Index (PASI) score at baseline and after 16, 24, 52, 104 and 156 weeks of treatment. RESULTS: PASI90 was achieved by all the patients in week 16 and remained stable until the end of the study. PASI100 has been achieved by 55.1% of patients at weeks 16 and by 81.3% at week 104. A statistically significant difference has been showed between baseline and all the other time points (P < 0.0001) for PASI score. A similar trend was observed for Visual Analogue Scale score and Dermatology Life Quality Index score. CONCLUSIONS: Ixekizumab was effective and with a good safety profile in psoriatic patients over 65 years. No significant adverse events were reported.

How to integrate surgery and targeted therapy with biologics for the treatment of hidradenitis suppurativa: Delphi consensus statements from an Italian expert panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified ten areas of interest based on published evidence and personal experience: 1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); 2) tailoring surgery to HS characteristics; 3) wide local excision; 4) pre-surgery biologic treatment; 5) concomitant biologic and surgical treatments; 6) pre- and post-surgery management; 7) antibiotic systemic therapy; 8) biologic therapy after radical surgery; 9) management of adverse events to biologics; 10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

Long-Term Persistence Rate of Secukinumab in Psoriatic Patients: A Six-Year Multicenter, Real-World Experience, Retrospective Study.

Background: Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods: This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results: Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-naïve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (±9.1) to 0.7 (±1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions: This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term.

Extracellular vescicles in psoriasis: from pathogenesis to possible roles in therapy.

Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (i.e., IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed.

Rapid response on facial psoriasis to bimekizumab: case series.

Psoriasis is a chronic inflammatory disease that can affect any part of the body but, when it appears in certain areas, like the face, it can have a very significant psychological impact. Biologics, in particular IL-17 and IL-23 drug inhibitors, have shown relevant clinical efficacy in the management of psoriatic lesions in difficult-to-treat areas. In post hoc analysis of phase III trials in plaque psoriasis, bimekizumab has shown safety and complete clearance of high-impact areas. However, these studies did not focus on the effect of bimekizumab on facial lesions. Therefore, this case series represents the first clinical real-life experience of rapid and successful management of facial psoriasis with bimekizumab in six patients.

Successful Treatment with Bimekizumab of a Psoriatic Patient Undergoing Hemodialysis: A Case Report and Review of the Literature.

Background/Objectives: Treating psoriasis patients requires the consideration of potential underlying complications like latent viral infections and chronic kidney disease, which may influence therapy selection. Case presentation: A patient with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) was successfully treated with bimekizumab, an IgG1 humanized monoclonal antibody inhibiting interleukin (IL)-17A and IL-17F. This case appears to be the first documented instance of effective anti-IL-17A/IL-17F antibody treatment in a psoriasis patient undergoing HD, with a sustained positive response for eight months. Discussion: Studies indicate the comparable pharmacokinetics, efficacy, and safety of certain psoriasis drugs in patients with chronic kidney disease (CKD) and those with normal renal function. The positive clinical outcome observed following treatment with bimekizumab aligns with the existing literature on this topic. However, further studies are needed to objectively evaluate the pharmacokinetics, efficacy, and safety of this drug in this specific setting. Conclusions: This documented case represents the first known use of bimekizumab to treat psoriasis in patients undergoing dialysis, suggesting its potential effectiveness and safety in this population.

18F-FDG PET-CT Scans in Oncology Patients Treated with Hyaluronic Acid Filler: Not Always a Pitfall.

The use of hyaluronic acid (HA) fillers in oncology patients undergoing PET-CT scans is a topic of debate due to potential interference with imaging accuracy. A 54-year-old female, postmelanoma metastasectomy in the parotid region with subsequent facial nerve palsy (FNP), received HA filler injections for facial symmetry and functional restoration. Follow-up PET-CT scans showed no interference or artifacts attributable to HA injection, allowing for accurate imaging results. This case suggests that HA fillers administered in oncology patients may not universally pose challenges or disrupt PET-CT imaging interpretation. Due to the possible false positives induced by fillers, the inclusion of aesthetic treatments in patients' anamnesis is a crucial step to accurately interpret PET-CT images. Although maintaining high level of caution in interpreting PET-CT results after filler injection is essential, our case emphasizes the safety of this procedure in oncology patients undergoing follow-up PET-CT scans.

Epidemiology, Characteristics of Disease, and Unmet Needs of Patients with Generalized Pustular Psoriasis: A Large Italian Delphi Consensus.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and chronic, debilitating skin condition characterized, in its acute flare phase, by clinically severe and potentially life-threatening systemic manifestations. Data on GPP are still scanty, particularly in Europe and at a national level. The aim of this study was to provide expert indications on several disease-related and patient-related aspects of GPP, with specific focus to the Italian context. METHODS: We conducted an iterative eDelphi study following the recommended criteria for reporting methods and results. After a thorough bibliographic review aimed to identify unknown or controversial issues in GPP, the following areas were investigated through a few specific questions/statements for each area: (1) disease epidemiology; (2) disease characteristics, with specific interest toward GPP flares; (3) diagnosis and diagnostic delay; (4) GPP treatment; (5) GPP patient journey and use of healthcare resources in Italy; (6) unmet needs and quality of life. An Executive Board of 9 principal investigators revised and approved the topics to be examined and overviewed the whole project. A total of 35 experts from different Italian areas, including 34 board-certified Italian dermatologists and 1 representative of patients' associations, took part in the study. RESULTS: A high agreement in responses from Italian experts emerged during two eDelphi iterations on - among several other aspects - GPP prevalence and incidence in Italy, use of European Rare and Severe Psoriasis Expert Network diagnostic criteria, flare frequency and duration, best diagnostic and care pathway, and main unmet needs of Italian patients. On the other hand, a broad spectrum of treatments (of different drug classes) was reported both in the acute and chronic phases of GPP, and no consensus on the issue was thus achieved. CONCLUSIONS: Consensus findings from this Delphi study of GPP experts may be useful to fill gaps of knowledge and improve awareness of this rare disease, as well as to help clinical and public health management of GPP in Italy.

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.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

The Prognostic Role of [18F]FDG PET/CT in Patients with Advanced Cutaneous Squamous Cell Carcinoma Submitted to Cemiplimab Immunotherapy: A Single-Center Retrospective Study.

Background: Baseline 2-deoxy-2[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography (PET)-derived parameters and 12-week metabolic response were investigated as prognostic factors in advanced cutaneous squamous cell carcinoma (cSCC) submitted to cemiplimab immunotherapy. Materials and Methods: Clinical records of 25 cSCC patients receiving cemiplimab, submitted to [18F]FDG positron emission tomography/computed tomography (PET/CT) at baseline and after ∼12 weeks, were retrospectively reviewed. The Kaplan-Meier (KM) method was applied to analyze differences in event-free survival (EFS), and Cox regression analysis was employed to identify the prognostic factors. Results: At the 12-week PET/CT evaluation, 16 patients (64%) were classified as responders (complete or partial response) and 9 (36%) as nonresponders ("unconfirmed progressive metabolic disease") according to immune PET Response Criteria in Solid Tumors (iPERCIST). By KM analysis, baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) significantly correlated with the EFS (p < 0.05). Furthermore, the KM analysis showed that the lack of metabolic response at 12 weeks was associated with meaningfully shorter EFS (7.2 ± 1 months in nonresponders vs. 20.3 ± 2.3 months in responders). In Cox multivariate analysis, metabolic response at 12 weeks remained the only predictor of the EFS (p < 0.05). Conclusions: Baseline tumor load (i.e., MTV and TLG) and metabolic response at 12 weeks may have a prognostic impact in cSCC patients treated with cemiplimab.

Supraorbital Basosquamous Carcinoma Treated with Cemiplimab Followed by Sonidegib: A Case Report and Review of the Literature.

Basal cell carcinoma (BCC) is a skin cancer with low local aggressiveness and a low tendency to metastasize. Basosquamous Carcinoma (BSC) represents an aggressive histological subtype of BCC with intermediate features between Squamous Cell Carcinoma (SCC) and BCC. Cemiplimab is currently approved as first-line therapy in SCC and second-line therapy in BCC patients who have progressed on or are intolerant of a Hedgehog pathway Inhibitor (HHI). Our study describes the case of a 59-year-old man with BSC who was successfully treated with 5 cycles of Cemiplimab as first-line therapy and Sonidegib as second-line therapy. Currently, the efficacy of Cemiplimab against BSC and other histopathological subtypes of BCC has not been fully elucidated, as has the role of sequential or combination therapy with Cemiplimab and HHI in the management of BSC. The aim of this case report is to highlight the need to outline the use of checkpoint inhibitors in BCCs and focus attention on the synergistic role of Cemiplimab and HHIs in such a controversial entity as BSC.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.

Analysis of predictive factors influencing dupilumab continuation rate in adult patients with atopic dermatitis: results from an Italian multicenter study.

OBJECTIVES: The purpose of this study was to analyze the drug survival rate of dupilumab up to 2 years in a large real-world cohort of adult patients affected by moderate/severe atopic dermatitis (AD), and to investigate the clinical, demographic and predictive factors influencing the patients' treatment persistence. MATERIAL AND METHODS: This study included adult patients affected by moderate-to-severe AD treated with dupilumab for at least 16 weeks who visited 7 dermatologic outpatient clinics in Lazio, Italy, from January 2019 until August 2021. RESULTS: A total of 659 adult patients (345 male [52.3%], mean age: 42.8 years) with an average treatment duration of 23.3 months were enrolled in the study. Overall, 88.6% and 76.1% of patients were still on treatment after 12 and 24 months, respectively. The drug survival rate for discontinuation due to AEs and dupilumab ineffectiveness was 95.0% at 12 months and 90.0% at 24 months. The main reasons for drug discontinuation included inefficacy (29.6%), failed compliance (17.4%), persistent efficacy (20.4%) and adverse events (7.8%). Adult AD onset (≥18 years) and EASI score severity measured at the last follow-up visit were the only factors significantly associated with lower drug survival. CONCLUSION: This study revealed an increased cumulative probability of dupilumab survival at 2 years, reflected by a sustained effectiveness and a favorable safety profile of the drug.

Psoriasis induced by first­line pembrolizumab in metastatic non­small cell lung cancer: A case report.

Therapeutic options for non-small cell lung cancer (NSCLC) have changed with the introduction of immune checkpoint inhibitors. Immunotherapy is generally well tolerated, but can also be associated with severe adverse events, such as the development of new autoimmune diseases. In patients without a history of autoimmune diseases, psoriasis caused by immunotherapy treatment is rarely described in the literature. The present study describes the case of a 68-year-old man with metastatic NSCLC that started chemoimmunotherapy with carboplatin plus pemetrexed plus pembrolizumab. After two cycles of therapy, the patient developed a G3 maculopapular rash. Biopsy confirmed psoriasis and pembrolizumab treatment was discontinued. At the last follow up, the patient was still on maintenance therapy with pemetrexed alone, which is well tolerated. Psoriasis has rarely been reported as an immune-related adverse event. Although the patient had to stop the immunotherapy treatment, the patient is still exhibiting a response to it. Notably, it has previously been described how skin toxicities are associated with a better outcome. Other studies need to be conducted to identify the risk and predictive factors associated with severe immune adverse events and objective response.