Real-life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104-week multicenter retrospective study - IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Guselkumab is a fully human monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. [Correction added on [28-02-2023], after first online publication: 'humanized monoclonal antibody' has been changed to 'fully human monoclonal antibody' in the preceding sentence.] OBJECTIVES: We conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting. METHODS: Our retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centres, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered. RESULTS: At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI ≤2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study. CONCLUSION: Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in 'real-life' clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104.

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional longitudinal study of real-life clinical practice) study.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.

Secukinumab Exhibits Sustained and Stable Response in Patients with Moderate-to-Severe Psoriasis: Results from the SUPREME Study.

Secukinumab, a fully human monoclonal antibody, neutralizes interleukin-17A, a cornerstone cytokine driving the multiple manifestations of psoriasis. This post-hoc analysis of the SUPREME study was performed to determine the sustainability of response to secukinumab in terms of Psoriasis Area and Severity Index (PASI) 90 in patients with moderate-to-severe plaque psoriasis. Based on PASI 90 response at week 16, patients were stratified as PASI 90 responders (PASI90R, n = 337) or non-responders (PASI90NR, n = 72). At week 20, 94.2% (n = 295/313) achieved PASI 90/100 response in PASI90R, with response maintained through week 48 (89.6%, n = 189/211). An increased proportion of patients achieved PASI 90/100 response in PASI90NR (week 20: 29.9%, n = 20/67; week 48: 57.1%, n = 20/35). Overall, 64.4% patients achieved absolute PASI score = 0 at week 24 with response sustained to week 48 (66.9%). Secukinumab showed sustained and stable efficacy in maintaining PASI 90 response in patients with moderate-to-severe plaque psoriasis up to week 48.

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

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

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.

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.

Secukinumab demonstrates improvements in absolute and relative psoriasis area severity indices in moderate-to-severe plaque psoriasis: results from a European, multicentric, retrospective, real-world study.

Objective: This European, multicentric, retrospective study aimed to collect data on secukinumab effectiveness in a real-world setting.Research design and methods: All psoriatic patients starting secukinumab between January 2016 and February 2017 in 11 European centers were followed until February 2018 and retrospectively evaluated.Main outcome measures: Secukinumab effectiveness was assessed by relative improvement from baseline of the Psoriasis Area Severity Index (PASI) and absolute PASI score modifications throughout 52 weeks of therapy. Additionally measures assessing effectiveness were used, including improvements of body surface area (BSA) and Dermatology Life Quality Index (DLQI).Results: Out of the 330 patients with potentially 52-week treatment duration, naïve to biologics patients showed greater probability to achieve PASI score of ≤1, ≤2, ≤3, and ≤5 at week 12, compared to bio-experienced patients (45.86% vs. 27.17%, 62.42% vs. 42.42%, 73.89% vs. 57.80%, and 84.08% vs. 74.57%, respectively). The greater effectiveness of secukinumab treatment in bio-naïve patients was confirmed at week 24 and 52.Conclusions: In this real-world experience, secukinumab was proven effective in treating psoriasis patients throughout a 52-weeks observation period, with higher response in bio-naïve patients. This study may contribute to defining the clinical profile of secukinumab best-responders.