Successful use of tralokinumab for the treatment of atopic dermatitis on the genitals.

BACKGROUND: Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient's quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area. OBJECTIVE: to evaluate the efficacy of tralokinumab in AD patients with genital involvement. METHODS: Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16. RESULTS: out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores. CONCLUSION: despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement.

Long-Term Effectiveness and Safety of Ixekizumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: A Five-Year Multicenter Retrospective Study-IL PSO (Italian Landscape Psoriasis).

INTRODUCTION: The introduction of biological therapies has revolutionized the treatment of moderate-to-severe plaque psoriasis. In particular, ixekizumab, an inhibitor of interleukin-17A, has shown great results in terms of efficacy and safety in both clinical trials and real-world experiences. However, there is a lack of long-term real-world data available for ixekizumab. METHODS: We conducted a multicenter real-life study to evaluate the effectiveness and safety of ixekizumab in patients with moderate-to-severe plaque psoriasis. Psoriasis Area and Severity Index score (PASI) was collected at baseline and after 1, 2, 3, 4, and 5 years. The occurrence of any adverse events was recorded at each time point. RESULTS: We enrolled 1096 patients treated with ixekizumab for at least 1 year. At week 52, the percentages of PASI 90 and PASI 100 were 85.04% and 69.07%, respectively. After 5 years of treatment with ixekizumab, out of 145 patients, a PASI 90 response was achieved by 86.90% of patients, while complete skin clearance was reached by 68.28% of patients. We did not observe any new significant safety findings throughout the study period. CONCLUSION: This study supports the long-term effectiveness and safety of ixekizumab in a real-world setting.

OPT-In; Optimized Patient Treatment Outcomes in Plaque Psoriasis: A 3-Year State-Transition Treatment-Sequencing Model in the Italian Setting.

INTRODUCTION: There are several treatment options for plaque psoriasis (PsO), but uncertainty remains around the optimal sequencing of treatments. The aims of this study were to investigate how adopting a best-treatment-first treatment sequence impacts patient outcomes and healthcare systems and to quantify the cost of treatment failure to the healthcare system. METHODS: A 3-year state-transition treatment-sequencing model which identifies all possible treatment sequences in PsO was adapted to the Italian healthcare setting. Treatments considered in the model are those with European Medicines Agency marketing authorization and reimbursement in Italy as of December 2022. Italian market share data (2019-2021) and list prices (2022) informed the current prescribed sequences; these sequences were compared against all possible sequences to determine opportunities for improvement. Both the national perspective in Italy as well as the local perspective from seven regions were considered. The cost of treatment failure was informed through a questionnaire circulated to Italian dermatologists. RESULTS: Overall, 1284 possible treatment sequences are possible when four lines of treatment are considered for patients with moderate-to-severe PsO in Italy. Within the estimated range of treatment failures across those sequences (0.97-2.56 per patient over 3 years), current prescribing behavior from the national perspective suggests patients will face 1.44 failures on average; this highlights the potential for improvement. For every treatment failure, the cost borne by the Italian National Healthcare Service (NHS) is €676.80. Overall, prescribing more optimized treatment sequences results in a 22.95% reduction in failures with a 2.27% increase in costs. The regional analyses found similar trends. CONCLUSIONS: Results suggest that selecting the most effective treatment sequences for incident patients provides the greatest opportunity to reduce treatment failures and maximize patient outcomes with a modest impact on costs. While regional variations exist, there is room for improvement across the board, which could translate to more efficient local healthcare systems.

Comparative effectiveness of tildrakizumab 200 mg versus tildrakizumab 100 mg in psoriatic patients with high disease burden or above 90 kg of body weight: a 16-week multicenter retrospective study - IL PSO (Italian landscape psoriasis).

PURPOSE: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight. MATERIALS AND METHODS: Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2. RESULTS: After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively. CONCLUSIONS: Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.

Autoreactivity to self-antigens LL37 and ADAMTSL5 influences the clinical response to risankizumab in psoriatic patients.

The autoantigens LL37 and ADAMTSL5 contribute to induce pathogenetic T-cells responses in a subset of psoriatic patients. Whether the presence of LL37-and/or ADAMTS5-reactive T-cells influences the clinical response to treatment is still unknown. The aim of the study is to evaluate the clinical responses to the anti-IL-23 risankizumab in LL37 and/or ADAMTSL5-reactive patients in comparison with non-reactive ones and to assess whether genetics (HLA-Cw06.02) or BMI influences the response to treatment. Patients were screened at baseline for the presence of circulating LL37 or/and ADAMTSL5-reactive T-cells and were treated as per protocol with risankizumab. Effectiveness data (PASI scores) were collected at weeks 4, 16, 28, 40 and 52. Data were also analyzed based on HLA-Cw06.02 status and BMI. The overall response to treatment of patients with autoreactivity to LL37 or ADAMTSL5 did not differ compared to the non-reactive cohort as measured as PASI75/90/100 at different time points; however, subjects that had autoreactive T-cells to both LL37 and ADAMTS5 demonstrated suboptimal response to treatment starting at week16. HLA-Cw06:02+ patients demonstrated faster response to risankizumab at week 4 compared to HLA-Cw06:02-. Additionally, the response to treatment was influenced by the BMI with slower responses seen in overweight and obese patients at week 4 and week16. In conclusion, while the presence of either LL37-and ADAMTS5-reactive circulating T-cells do not influence the clinical response to risankizumab, the presence of the double reactivity to both LL37 and ADAMTS5 decreases the clinical responses. Moreover, we evidenced that HLA-Cw06+ respond faster to IL-23 inhibition and that BMI, associated to autoreactivity, can influence the speed in response.

Association of disease duration and PASI response rates at week 12 in patients with moderate-to-severe plaque psoriasis receiving biologics in the real-world psoriasis study of health outcomes (PSoHO).

PURPOSE: Currently, in the treatment of moderate-to-severe psoriasis (PsO) there is a lack of evidence demonstrating optimal biologic treatment response with respect to disease duration. The aim of this post-hoc analysis, using real world data from the Psoriasis Study of Health Outcomes (PSoHO), is to provide evidence if early intervention with biologics is associated with better treatment outcomes and if there is any difference among drug classes or individual biologics. MATERIALS AND METHODS: For this post-hoc analysis patients were categorised into two subgroups according to shorter (≤2 years) or longer (>2 years) disease duration. Analysis was performed on anti-interleukin (IL)-17A cohort vs other biologics cohort, anti-IL-17A vs other drug classes, and pairwise comparisons of ixekizumab vs individual biologics, provided that the statistical models converged. Analysis investigated the association of disease duration with the proportion of patients achieving 100% improvement in Psoriasis Area Severity Index score (PASI 100) at week 12. Adjusted comparative analyses, reported as odds ratio (OR), were performed using Frequentist Model Averaging (FMA) for each cohort or treatments within each subcategory of the subgroups. RESULTS: At week 12, anti-IL-17A and other biologics cohorts displayed minimal differences in numerical response rate for PASI 100 with respect to disease duration. The anti-IL-17A cohort showed a higher numerical PASI 100 response rate compared to the other biologic cohort irrespective of disease duration (≤2 years: 36.7% vs 21.8%; >2 years: 35.8% vs 21.9%). CONCLUSION: Overall, the results do not clearly indicate that treating patients early is critical in achieving optimal patient outcomes. Furthermore, patients treated with ixekizumab show numerically higher response rates relative to other individual biologics irrespective of disease duration.

A severe psoriasis flare after COVID-19 treated with risankizumab: complete skin clearance after 16 weeks.

The development of flares or new-onset of immune-mediated dermatologic diseases, including psoriasis, has occurred with the worldwide spreading of the COVID-19 pandemic. We report the case of a 38-year-old woman who came to our department with a severe flare of plaque psoriasis four weeks after SARS-CoV-2 infection. Her Psoriasis Area Severity Index was 25, and her Dermatology Life Quality Index was 18. Our initial decision was to prescribe acitretin, but the patients reported adverse events. For this reason, we started risankizumab with complete skin clearance after 16 weeks. The patient is still on treatment, and no adverse events have been reported to date.

Baseline Characteristics and mNAPSI Change from Baseline Scores Through Month 12 for Patients with Moderate-to-Severe Plaque Psoriasis and Concomitant Nail Psoriasis Treated with Biologics from PSoHO.

INTRODUCTION: Nail psoriasis is highly prevalent among patients with psoriasis yet remains one of the most challenging areas to treat. To better understand the treatment landscape for psoriatic nail disease, more studies are needed that compare the effectiveness of different biologics for patients with nail psoriasis. This study contributes to this objective by directly comparing the effectiveness of approved biologics in improving nail psoriasis for patients up to month 12 in a real-world setting. METHODS: Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. This study assessed the change in modified Nail Psoriasis Severity Index (mNAPSI) score from baseline to months 3, 6 and 12 for 763 patients and compared the effectiveness of anti-interleukin (IL)-17A biologics versus other approved biologics, as well as ixekizumab versus secukinumab, guselkumab, risankizumab and adalimumab. Comparative adjusted analyses used frequentist model averaging (FMA). Least square mean difference (LSMD) in mNAPSI scores are presented as observed. RESULTS: Irrespective of the severity of nail psoriasis at baseline, the anti-IL-17A cohort had greater mean mNAPSI reductions from baseline compared to the other biologics cohort through month 12, reaching significance at months 3 and 6 in the adjusted analysis. For patients with moderate-to-severe nail psoriasis, ixekizumab showed numerically higher mean reductions in mNAPSI scores compared to all other studied biologics, reaching significance versus guselkumab at all timepoints and risankizumab at month 6. CONCLUSION: This real-world study showed that patients with moderate-to-severe psoriasis and any severity of concomitant nail involvement had significantly faster and more substantial improvements in nail psoriasis up to month 6 in the anti-IL-17A cohort compared to the other biologics cohort. Of the individual biologics studied, ixekizumab showed the highest numerical improvements in nail psoriasis at month 12. TRIAL REGISTRATION: EUPAS24207.

Practical Use of Upadacitinib in Patients with Severe Atopic Dermatitis in a Real-World Setting: A Systematic Review.

Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies. Of these, 214 were excluded after reviewing their titles and abstracts. We then conducted a full-text review of 25 studies, of which 17 met our inclusion criteria and were therefore included in our systematic review. The analysis of real-world studies showed high effectiveness of upadacitinib, in terms of both clinical signs and subjective symptoms, in different patient populations, including those resistant to other treatments. No new significant safety concerns have emerged as compared to randomized clinical trials.

Management of Patients Affected by Moderate-to-Severe Atopic Dermatitis with JAK Inhibitors in Real-World Clinical Practice: An Italian Delphi Consensus.

INTRODUCTION: Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs. METHODS: Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements. RESULTS: Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements. CONCLUSION: Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient's phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events.

Effectiveness and Safety of Biological Therapies in Very Severe Plaque Psoriasis: A Real-Life Retrospective Study.

Psoriasis can have a significant impact on quality of life and productivity, especially with increased severity. However, there is limited evidence on biologics' efficacy in highly severe cases compared to moderate-to-severe ones. This study aimed to evaluate the effectiveness and safety of novel biological therapies in very severe psoriasis. We conducted a retrospective analysis on patients ≥ 18 years old affected by very severe psoriasis who had received a biological agent for at least 16 weeks. We used PASI to assess disease severity and effectiveness at weeks 16, 52, 104, and 156. Safety was evaluated by tracking treatment discontinuation rates and adverse events. This study included 29 males and 11 females, with a mean age of 55.80 years (SD 13.82). Cardiometabolic diseases were the most common comorbidities (25.00%). Twenty-eight (70.00%) patients had psoriasis involvement in at least one difficult-to-treat area. All patients completed 16 weeks of treatment. The mean PASI was 31.60 (SD 2.57) at baseline, 3.48 (SD 4.13) at week 16, 0.58 (SD 1.70) at week 52, 0.77 (SD 1.66) at week 104, and 1.29 (SD 2.12) at week 156. PASI90 and 100 were achieved by 52.50% and 30.00% of patients at week 16, by 96.15% and 80.77% at week 52, by 93.33% and 66.67% at week 104, and by 85.71% and 42.86% at week 156. PASIs ≤ 2 were achieved by 50.00% of patients at week 16, 88.46% at week 52, 86.67% at week 104, and 85.71% at week 156. Only two patients discontinued biologics due to complete remission, and mild AEs were reported by four patients. Our findings show that biologics are effective and well tolerated for treating very severe psoriasis, maintaining long-term effectiveness.

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 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 Psoriasis Area and Severity Index scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index, 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.

Effectiveness, Tolerability, and Drug Survival of Risankizumab in a Real-World Setting: A Three-Year Retrospective Multicenter Study-IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin-23. It has been approved for moderate-to-severe plaque psoriasis and has shown efficacy and safety in clinical trials and real-world experiences. This study aimed to evaluate the long-term effectiveness, safety, and drug survival of risankizumab in a real-life setting. MATERIALS AND METHODS: We included patients treated with risankizumab from January 2019 to February 2023. A Psoriasis Area and Severity Index score (PASI) was collected at weeks 0, 16, 28, 52, 104, and 156, when available. The occurrence of any adverse events was recorded at each visit. RESULTS: We enrolled 1047 patients. At week 52, a ≥90% improvement in PASI was observed in 81.44% of patients, with a continuous improvement throughout the study (88.99% and 99.07% at weeks 104 and 156, respectively). After three years of treatment, all patients involving the scalp, palms/soles, and genitalia and 95% of patients with nail psoriasis achieved a complete or almost complete skin clearance. No significant safety findings were observed, and 90.73% of the patients were still on treatment after 36 months. CONCLUSIONS: This study supports the long-term effectiveness and safety of risankizumab in a real-world setting, even in patients involving difficult-to-treat areas.

Effectiveness of ixekizumab for the treatment of moderate-to-severe plaque psoriasis with involvement of difficult-to-treat areas: A 52-week multicenter retrospective study.

Biological drugs have dramatically changed the approach to treating moderate-to-severe plaque psoriasis, achieving excellent skin clearance and safety outcomes. However, the management of difficult-to-treat areas (e.g., scalp, palms/soles, nails, and genitalia) still represents a challenge in psoriasis treatment. Data in the literature on difficult-to-treat sites are limited and, frequently, no specific analysis is performed during clinical trials. We conducted a 52-week, retrospective study to evaluate the effectiveness of ixekizumab in 120 patients with moderate-to-severe plaque psoriasis of at least one difficult-to-treat area (scalp, palmoplantar surfaces, nails, and genitalia). Ninety-nine patients had scalp psoriasis, 35 had involvement of the palms or soles, 27 were affected by genital psoriasis, and 22 patients reported involvement of the nails. After 1 year of treatment, 96% of patients with scalp involvement, 95.6% of patients with palmoplantar psoriasis, 95.2% of patients with genital psoriasis, and 85% of patients with nail involvement achieved a site-specific Physician's Global Assessment of 0 or 1 (clear or almost clear). No serious adverse events were observed during the study. Our study supports the effectiveness of ixekizumab in plaque psoriasis involving difficult-to-treat sites.

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.