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.

Dimethyl fumarate as a safe and effective therapy for recalcitrant psoriasis in comorbid patients.

Psoriasis is a chronic condition for which multiple therapies are currently available. In particular, in cases of moderate- severe psoriasis, traditional systemic drugs or the new biological drugs can be administered. However, the treatment of patients who require systemic therapy and have multiple comorbidities can be particularly complex. Some treatment options may be in fact contraindicated or may lose effectiveness over time, reducing the options available to the dermatologists. In such circumstances, dimethyl fumarate may represent a safe and effective choice, also in patients who have already attempted biological therapies. In this regard, we report the case of a patient with moderate-severe psoriasis treated over time with various therapies (including topicals, phototherapy, traditional and biological drugs) that were discontinued due to ineffectiveness or incompatibility caused by the occurrence of concomitant diseases, who finally achieved clinical remission with dimethyl fumarate.

Deferred time of delivery of biologic therapies in patients with stabilized psoriasis leads to a 'perceived satisfaction': a multicentric study.

OBJECTIVE: Thanks to their specificity of action, biologic drugs often lead to complete clearance of psoriatic lesions. In order to maintain its effectiveness, biological therapies cannot be discontinued. The aim of the study was to investigate the effect of widening the administration window of four biologic drugs, thus improving the quality of life of psoriatic patients and satisfying their desire to feel free from the disease, without loss of effectiveness. METHODS: We performed a multicentric cohort study considering patients with moderate-severe plaque psoriasis and/or arthropathic psoriasis treated with infliximab, adalimumab, etanercept or ustekinumab. The study group included patients with stabilized psoriasis in which the administration regimen of the biologic drug was deferred. The control group included psoriatic patients treated according the product monograph. RESULTS: The percentage of relapses in case of deferred administration intervals was comparable to that of standard administration intervals. The delayed administration modality got a good psychological consensus from the patients themselves, that reported a greater 'perceived satisfaction'. A consistent economic advantage was reported in case of prolonged administration intervals. CONCLUSIONS: The administration of biologic drugs with prolonged intervals maintains the same effectiveness as standard administration and produces a 'perceived satisfaction' in psoriatic patients.

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.

Impact of Body Mass Index on the Efficacy of Biological Therapies in Patients with Psoriasis: A Real-World Study.

BACKGROUND: The efficacy of biological therapies used for the treatment of chronic plaque psoriasis can be influenced by numerous variables including  body mass index (BMI). OBJECTIVE: This study aimed to evaluate the impact of BMI on the short-term and long-term efficacy of biological therapies in clinical practice and to identify the best therapeutic options in obese patients (BMI ≥ 30 kg/m2). METHODS: A multicentric retrospective study was conducted in patients who initiated a biological therapy during the period January 2006-December 2019. The proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index at weeks 12 and 24 was calculated also recording the 12- and 24-month drug survival as a measure of long-term efficacy, performing multivariate analyses to assess the impact of different variables. RESULTS: Five hundred and four patients with psoriasis were included. After 12 and 24 weeks, the proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index response was higher in patients with a BMI < 30 kg/m2 compared with those with a BMI ≥ 30 kg/m2 [54.90% vs 43.45% (p = 0.014) at week 12 and 66.84% vs 56.55% (p = 0.021) at week 24]. The Kaplan-Meier survival curves showed how obese patients had a higher probability of discontinuation due to a lack or loss of efficacy (p = 0.0192) compared with non-obese patients. The drug survival analysis also showed that BMI negatively affected the drug survival of secukinumab (odds ratio 1.27, p < 0.001) and ustekinumab (odds ratio 1.06, p = 0.050), while the long-term efficacy of adalimumab, etanercept, and ixekizumab was not influenced by BMI. CONCLUSIONS: Obesity (BMI ≥ 30 kg/m2) negatively affects the clinical response of biological drugs in psoriatic patients, with anti-interleukin drugs being more affected by BMI than anti-tumor necrosis factor drugs.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

Active pharmacovigilance program in patients affected by psoriasis and inflammatory bowel diseases
.

OBJECTIVE: To help identify adverse events (AEs) in new biologic therapies and to spread the culture of pharmaceutical surveillance among patients affected by psoriasis or inflammatory bowel disease (IBD). MATERIALS AND METHODS: This active pharmacovigilance program provided all patients with telephone follow-ups (FU), carried out by a clinical pharmacologist for a total duration of 1 year. Collected AEs were classified according to the MedDRA dictionary. RESULTS: 21 patients with psoriasis and 10 patients with IBD were enrolled. In our sample, the AEs reported were frequent but mild, underlining the crucial role of active pharmacovigilance in detecting minor AEs rarely spontaneously reported by the patients. CONCLUSION: According to our experience, a multidisciplinary team is recommended to manage complex therapies improving AE reporting and promoting greater therapeutic adherence.

Biological therapy in genital psoriasis in women.

Genital psoriasis (GenPs) is a frequent manifestation of psoriasis, causing distress, especially in women. We prospectively studied a population of 74 psoriatic women with severe and generalized psoriasis eligible to biologic therapy, to examine which biologic therapy is more effective on GenPs and to study possible associations between PASI severity and GenPs. Overall, 25/74 (34%) had GenPs: 6 received Ixekizumab, 7 Ustekinumab, 8 Adalimumab, 2 Secukinumab, 1 Etanercept, 1 Certolizumab. Therapies were administered based on PASI severity, independently from the presence of GenPs. Side effects, PASI score, sPGA-G scale for GenPs were recorded at time 0 and after 6 month of therapy. The mean sPGA-G scale value was 2.8 before treatment. After biologic therapy, all patients except one, improved of at least one point. Mostly, patients treated with anti-IL17 (Secukinumab, Ixekizumab) and anti-IL12/23 (Ustekinumab) improved. Mean PASI ranged from 10 to 16.3 before treatment. After 6 months of therapy, 4 anti-TNFα patients, 6 anti-IL17 and 1 anti-IL12/23, reached PASI 90. At time 0, no correlation between PASI and sPGA-G was visible (Pearson r = 0.10, p = .620). From our data, GenPs apparently responds favorably to IL17A inhibitors, but further studies, based on larger numbers of patients, are needed.

Serial biologic therapies in psoriasis patients: A 12-year, single-center, retrospective observational study.

BACKGROUND: Biologic therapy for psoriasis is effective but not always long-lasting and sometimes needs to be switched. OBJECTIVE: We aimed to evaluate the drug survival (ie, the time from initiation to discontinuation) of each biologic and the factors affecting survival to identify better switching strategies and improve drug survival. METHODS: In total, 195 psoriasis patients treated in our unit during 2006-2018 were retrospectively observed. Descriptive statistical analyses and logistic regression models were performed. Kaplan-Meier survival curves and multivariate Cox models adjusted for confounding variables were used to estimate and compare drug survival. RESULTS: Overall, 90.6% of patients achieved an ≥75% reduction in their baseline Psoriasis Area and Severity Index score. In 2018, the most frequently used biologic was ustekinumab (47/169, 27.8%). Patients with higher baseline Psoriasis Area and Severity Index scores were more likely to be switched (P = .0399, odds ratio 1.08). In naive patients, ustekinumab showed longer drug survival (>7.0 years), but in biologic-experienced patients, we found no significant differences in drug survival. Previous biologic therapies increased the need for switching (P = .014, hazard ratio 1.20). Switching between biologic classes yielded longer drug survival than switching within biologic classes (P = .003, hazard ratio 0.48). LIMITATIONS: As a single-center, retrospective real-life study, the data were not perfectly homogeneous. CONCLUSION: Switching between biologic classes might increase drug survival but retrospective studies designed ad hoc are needed to confirm this better switching strategy.