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

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

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, 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.

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.

Artificial Intelligence in Skin Cancer Diagnosis: A Reality Check.

The field of skin cancer detection offers a compelling use case for the application of artificial intelligence (AI) within the realm of image-based diagnostic medicine. Through the analysis of large datasets, AI algorithms have the capacity to classify clinical or dermoscopic images with remarkable accuracy. Although these AI-based applications can operate both autonomously and under human supervision, the best results are achieved through a collaborative approach that leverages the expertise of both AI and human experts. However, it is important to note that most studies focus on assessing the diagnostic accuracy of AI in artificial settings rather than in real-world scenarios. Consequently, the practical utility of AI-assisted diagnosis in a clinical environment is still largely unknown. Furthermore, there exists a knowledge gap concerning the optimal use cases and deployment settings for these AI systems as well as the practical challenges that may arise from widespread implementation. This review explores the advantages and limitations of AI in a variety of real-world contexts, with a specific focus on its value to consumers, general practitioners, and dermatologists.

Safety of omalizumab for chronic urticaria during pregnancy: a real-life study.

BACKGROUND: Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data showed that most CSU treatments in pregnant patients were second-generation H1-antihistamines (sgAHs), while data on safety of omalizumab are scant. OBJECTIVES: To evaluate the efficacy and safety of omalizumab in patients with severe CSU refractory to sgAHs, either becoming pregnant during treatment or starting the drug during pregnancy, in a routine clinical practice setting. METHODS: We conducted a retrospective study on women aged ≥18 years, pregnant, receiving 1 or more doses of omalizumab at any time during pregnancy, or taking omalizumab at the time of conception or during the 8 weeks before conception. RESULTS: Twenty-nine pregnant patients were evaluated in the study: 23 (79.31%) conceived a child during omalizumab therapy (group A), while 6 (20.69%) started omalizumab therapy during pregnancy (group B). Among group A, we observed 23 births (21 live-born singletons and 1 live-born twin pair) and 1 miscarriage. Fifteen out of 23 (65.22%) patients discontinued omalizumab after discovering the pregnancy state, while 8/23 patients (34.78%) were exposed to omalizumab during the entire pregnancy. In the group B, omalizumab was introduced at 10.83 ± 3.60 weeks of gestation and all patients were exposed to it until the end of pregnancy. In this group, there were 7 live-born infants (5 singletons and 1 twin pair). No AEs, pregnancy complications or congenital anomalies of newborns were recorded in both groups. CONCLUSIONS: Omalizumab for CSU treatment before and during pregnancy does not seem to negatively affect maternal or fetal outcomes.

Effectiveness and Safety After a Switch to Tildrakizumab: A Real World Multicenter Italian Study in Psoriasis.

INTRODUCTION: Tildrakizumab is a humanized IgG1κ monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, approved in 2018 for the treatment of patients with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: This study aimed to evaluate the effectiveness, safety and survival of tildrakizumab in the medium term (48 weeks) in psoriatic patients failure to previous biologic treatment in a real world setting. METHODS: This was a retrospective, multicenter observational study that included adult patients with moderate-to-severe plaque psoriasis, failure to previous biologic therapy, consecutively treated with tildrakizumab. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) values were recorded at baseline, at 12 and 48 weeks of treatment. Safety and tolerability of tildrakizumab were investigated by examining the presence of any adverse events. RESULTS: Overall 51 patients were enrolled. Baseline disease severity was moderate to severe with a mean PASI score of 19.2 ± 8.5, mean BSA of 16 ± 10.4, and mean Dermatology Life Quality Index (DLQI) of 18.2 ± 6.8. A significant reduction in the mean PASI score was detected at 12 weeks of tildrakizumab therapy (3.5 ± 2.7, P < 0.001), with a further improvement at week 48 (0.6 ± 1.5, P < 0.001). At week 12, there was a great improvement in BSA score for all groups (P <0.001) with further increase at week 48. The effectiveness was confirmed also by DLQI assessment, with a significant decrease at week 12 and even more at week 48 (P <0.001). CONCLUSIONS: This study confirms the effectiveness of tildrakizumab in daily clinical practice in patients with moderate-to-severe plaque psoriasis.

Ixekizumab is effective in the long-term management in moderate-to-severe plaque psoriasis: results from an Italian retrospective cohort study (the LOTIXE study).

PURPOSE: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A approved for the treatment of moderate-to-severe plaque psoriasis. The objective of this study was to describe the real-world long-term effectiveness of ixekizumab in patients with plaque psoriasis in Italy. MATERIALS AND METHODS: A retrospective study was conducted in patients affected by moderate-to-severe plaque psoriasis who were continuously treated with ixekizumab for at least 12 months. Patient data was obtained at 4-weeks, 12-weeks and 6-, 12-, 18- and 24-months after baseline (June 2017 and September 2019) from 10 sites. Results were analyzed by complete case approach, with sensitivity analysis performed to evaluate the impact of missing data. RESULTS: A total of 198 patients were enrolled in the study. At Month 24, 94.3% of patients achieved PASI75 response, while 85.1 and 71.8% achieved PASI90 and PASI100, respectively; and 91.1% of the patients achieved absolute PASI score ≤2. Patients experienced psoriasis improvement at 4 weeks after starting treatment, and improvement was maintained with continued ixekizumab use. The quality of life of patients also improved significantly starting at Week 12, with sustained effect in the long term. CONCLUSION: This 24-month observational cohort study confirmed that ixekizumab is effective in the long-term management of patients with moderate-to-severe plaque psoriasis.

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

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

Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study-IL PSO (Italian landscape psoriasis).

Introduction: Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited. Methods: The aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients' demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded. Results: At week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab. Conclusion: Our data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.

Long-term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis in a Real-world Setting: An Interim Analysis Through 48 Weeks of Observation.

BACKGROUND: Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. METHODS: This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. RESULTS: One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. CONCLUSION: This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change.

The potential role of serum polyclonal free light chains as markers of immune activation in psoriatic patients.

BACKGROUND: Polyclonal free light chains (FLCs) of immunoglobulins include κ and λ chains and represent a sensitive marker of activation and/or dysfunction of the immune system. OBJECTIVES: The aim of this study was to investigate the role of FLCs as markers of immune activation in the management of psoriatic patients treated with biologics. MATERIALS & METHODS: The overall study population included 45 patients affected by mild-to-severe psoriasis with either ongoing biological treatment or without any current systemic therapy. Peripheral blood samples were taken from all patients and 10 healthy subjects in order to determine immunoglobulins, light chains and FLCs by quantitative nephelometric assay. Moreover, antinuclear antibodies (ANA) were detected by immunofluorescence. RESULTS: Psoriatic patients showed significant increased levels of κ and λ FLCs compared to healthy controls. Interestingly, κ and λ FLCs values were significantly increased only in psoriatic patients with ongoing biological treatment and, in particular, in responder subjects. Furthermore, both κ and λ FLCs significantly correlated with duration of therapy. For patients with FLC levels above normal range and under biological treatment for more than 12 months, the odds of being ANA+ was greater relative to patients with FLC levels above normal range but under biological treatment for less than 12 months. CONCLUSIONS: Increased FLC levels may represent a marker of immune reactivation in psoriatic patients treated with biologic agents. We suggest that determining FLC levels has clinical relevance, with a cost/benefit ratio justifying such evaluation in the clinical management of psoriasis.