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.

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.

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.

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.

Real-World Experience of Methotrexate in the Treatment of Skin Diseases: an Italian Delphi Consensus.

BACKGROUND: After decades of use, methotrexate displays an established safety and efficacy profile in both in-hospital and outpatient settings. Despite its widespread use, there is surprisingly little clinical evidence to guide daily practice with methotrexate in dermatology. OBJECTIVES: To provide guidance for clinicians in daily practice for areas in which there is limited guidance. METHODS: A Delphi consensus exercise on 23 statements was carried out on the use of methotrexate in dermatological routine settings. RESULTS: Consensus was reached on statements that cover six main areas: (1) pre-screening exams and monitoring of therapy; (2) dosing and administration in patients naïve to methotrexate; (3) optimal strategy for patients in remission; (4) use of folic acid; (5) safety; and (6) predictors of toxicity and efficacy. Specific recommendations are provided for all 23 statements. CONCLUSIONS: In order to optimize methotrexate efficacy, it is essential to optimize treatment using appropriate dosages, carrying out a rapid drug-based step-up on a treat-to-target strategy and preferably using the subcutaneous formulation. To manage safety aspects appropriately, it is essential to evaluate patients' risk factors and carry out proper monitoring during the course of treatment.

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.

Drug survival of IL-12/23, IL-17 and IL-23 inhibitors for moderate-to-severe plaque psoriasis: a retrospective multicenter real-world experience on 5932 treatment courses - IL PSO (Italian landscape psoriasis).

Introduction: The development of several effective biological drugs for moderate-to-severe plaque psoriasis has dramatically changed the lives of patients. Despite the wide use of interleukin (IL) inhibitors, limited data are available to date regarding long-term treatment persistence. Method: This multicenter retrospective real-world study evaluated 5932 treatment courses across 5300 patients, all treated with interleukin inhibitors. Drug survival was expressed by using the Kaplan-Meier estimator for each biological drug at 6, 12, 24, 36 and 48 months. We also stratified by discontinuation associated with primary or secondary ineffectiveness. Results: In our study, the most prescribed drugs were secukinumab (1412), ixekizumab (1183), and risankizumab (977). After four years of follow-up, risankizumab emerged as the treatment with the highest drug survival overall, as 91.6% of patients were still on treatment. The overall probability of drug survival at four years was comparable for tildrakizumab (83.5%), ixekizumab (82.6%), guselkumab (82.4%) and brodalumab (81.8%). When evaluating only patients who discontinued the treatment because of ineffectiveness, once again risankizumab was the molecule with the highest drug survival at 4 years (93.4%), this time followed by ixekizumab (87%). Our study, in which all IL inhibitors were adequately represented, confirmed a slightly better treatment persistence for IL-23 inhibitors, consistent with other real-world studies. Conclusion: Our experience showed that IL-23 inhibitors, and risankizumab in particular, had a higher probability of drug survival overall during a 4-year follow-up. Risankizumab and ixekizumab were less likely to be discontinued because of ineffectiveness after four years.

Real life long-term efficacy and safety of ixekizumab in moderate-to-severe psoriasis: A 192 weeks multicentric retrospective study-IL PSO (Italian landscape psoriasis).

Psoriasis is one of the commonest inflammatory skin diseases determining a very high impact on patients' quality of life and daily activities and relationships. Several biologic therapies have been approved through the years for the treatment of moderate-to-severe plaque psoriasis, and efficacy and safety profile have been analyzed in clinical trials. Ixekizumab is an immunoglobulin G subclass 4 monoclonal antibody that selectively targets and binds IL-17A with high specificity and affinity. Inhibiting IL-17A activity, ixekizumab reduces and turns down levels of inflammation, resulting in the clinical improvement of the disease. Long-term efficacy and safety profile of ixekizumab have been investigated and reported in the UNCOVER trials, but in literature there are only few studies based on real life experience. We present the efficacy and safety profile of ixekizumab in a cohort of 779 patients affected by moderate-to-severe plaque psoriasis and treated with ixekizumab in 11 Italian dermatology hospitals, with a follow-up of care until 192 weeks.

Predicting Secukinumab Fast-Responder Profile in Psoriatic Patients: Advanced Application of Artificial-Neural-Networks (ANNs).

BACKGROUND: Drug resistance to biologics in psoriasis therapy can occur – it may be acquired during a treatment or else present itself from the beginning. To date, no biomarkers are known that may reliably guide clinicians in predicting responsiveness to biologics. Biologics may pose a substantial economic burden. Secukinumab efficiently targets IL-17 in the treatment of psoriasis. OBJECTIVE: To assess the “fast responder” patient profile, predicting it from the preliminary complete blood count (CBC) and clinical examination. MATERIALS AND METHODS: From November 2016 to May 2017 we performed a multicenter prospective open label pilot study in three Italian reference centers enrolling bio-naive plaque psoriasis patients, undergoing the initiation phase secukinumab treatment (300mg subcutaneous at week 0,1,2,3,4). We define fast responders as patients having achieved at least PASI 75 at the end of secukinumab induction phase. Clinical and CBC data at week 0 and at week 4 were analyzed with linear statistics, principal component analysis, and artificial neural networks (ANNs), also known as deep learning. Two different ANNs were employed: Auto Contractive Map (Auto-CM), an unsupervised ANNs, to study how this variables cluster and a supervised ANNs, Training with Input Selection and Testing (TWIST), to build the predictive model. RESULTS: We enrolled 23 plaque psoriasis patients: 19 patients were responders and 4 were non-responders. 30 attributes were examined by Auto-CM, creating a semantic map for three main profiles: responders, non-responders and an intermediate profile. The algorithm yielded 5 of the 30 attributes to describe the 3 profiles. This allowed us to set up the predictive model. It displayed after training testing protocol an overall accuracy of 91.88% (90% for responders and 93,75% for non-responders). CONCLUSIONS: The present study is possibly the first approach employing ANNs to predict drug efficacy in dermatology; a wider use of ANNs may be conducive to useful both theoretical and clinical insight. J Drugs Dermatol. 2020;19(12) doi:10.36849/JDD.2020.5006.

The EPIPSOFIRE project: a preliminary report.

Psoriatic arthritis (PsA) is a musculoskeletal condition complicating psoriasis that can lead to joint deformity and disability; however, psoriatic patients may suffer from other kind of arthropathies that could be confused with PsA by nonrheumatologists. Our aim was to determine the prevalence of PsA and to determine the prevalence of other musculoskeletal conditions in a cohort of psoriatic patients. In this cohort, musculoskeletal discomfort was frequently reported, while inflammatory disorders were detected in <4% of subjects. The cohort lacked subjects with very long-standing psoriasis duration (>20 years) or severe cutaneous disease. Because musculoskeletal discomfort symptoms affected about 62% of patients, other disorders, particularly morphologic conditions, need careful evaluation in psoriasis subjects.

Not simply a matter of psoriatic arthritis: epidemiology of rheumatic diseases in psoriatic patients.

This study investigated the occurrence of rheumatic conditions (RCs) in a psoriasis (PSO)-dedicated dermatological clinic. PSO subjects with musculo-skeletal discomfort, and/or carrying signs (articular/systemic, even asymptomatic) of RCs; and/or suffering flares of previously established psoriatic arthritis (PsA) were referred to rheumatologist for evaluation. Laboratory tests/imaging were performed as needed. Categorization adhered to RCs classification endorsed by the Italian Society of Rheumatology. Of the 1,200 psoriatic subjects, 277 (23.1 %) were enrolled (146 females). The mean age was 55.7 years (range 21-81), PSO duration was 13.5 years (range 0-62). Thirty-seven patients (13.4 %) were asymptomatic. On an average, 92 (7.6 %) patients/year were evaluated, of whom 79.4 % näive to rheumatological consultations (NRC). Osteoarthritis (OA) and PsA (isolated or combined) showed the highest prevalence, with 156 (56.3 %) and 110 cases (39.7 %), respectively. Among NRC subjects, the mean PsA annual incidence was 29.5 % (standard error of the mean ±5.4 %). Other RCs, isolated or associated with PsA/OA, were diagnosed in 31 cases (11.2 %). Thirty-two subjects (11.5 %) had arthralgias, 20 of whom due to congenital/mechanical disorders, the remaining were unclassifiable. In conclusion, the largest part (88.5 %) of PSO subjects referred to rheumatologist showed some RCs. On annual basis, 29.5 % of näive enrolled patients were diagnosed as PsA.