BACKGROUND:Psoriasis is a chronic inflammatory disease with multiple comorbidities, including an increased risk of major adverse cardiovascular events (MACE). There is limited and contradictory evidence comparing the impact of systemic treatments for psoriasis on MACE. OBJECTIVES:To evaluate the incidence of MACE associated with each systemic treatment used for patients with psoriasis and compare these rates to those observed with methotrexate (MTX). METHODS:We conducted a prospective cohort study using data from the BIOBADADERM registry. Propensity score matching was used to adjust for baseline differences between treatment groups. We calculated the incidence rate (IR) of MACE for each systemic treatment class, including biologics (anti-TNF, IL-12/23, IL-17 and IL-23 inhibitors), conventional systemic therapies (MTX, cyclosporine, dimethyl fumarate and acitretin) and apremilast (APR). The IR for each group was compared to those observed in patients treated with MTX using Poisson regression models adjusted for potential confounders, with 95% confidence intervals (95% CI). The primary outcome was the adjusted incidence rate ratios (IRR) for MACE between patients receiving MTX and those receiving another systemic treatment. RESULTS:We analysed data from 5622 patients, 11,368 treatment cycles and 21,762 person-years (PYs). APR (IRR = 0.17; 95% CI, 0.04-0.70) and IL-17 (IRR = 0.43; 95% CI, 0.20-0.91) were associated with a significant reduction in the risk of MACE compared to MTX. Cyclosporine was associated with an increased risk of MACE (IRR = 3.59; 95% CI, 1.17-10.99) compared to MTX. The remaining systemic psoriasis treatments were not significantly associated with an increased or decreased risk of MACE. CONCLUSIONS:This real-world evidence study indicates a potential association between APR and IL-17 with a lower incidence of MACE, while CYC showed a higher incidence compared to MTX. These findings underscore the importance of considering cardiovascular outcomes when selecting systemic therapies for patients with psoriasis.

INTRODUCTION:The Inpsight Project, established in 2021, aimed to define the concept of well-being in patients with psoriasis from a holistic perspective. Well-being was defined as a multi-dimensional concept that includes achieving emotional balance, having adequate overall health and control of the disease, enjoying positive social relationships, and being satisfied with disease care. However, while these components are recognized as integral to the concept, their relative contribution to achieving optimal well-being remains unclear. To address this gap, the present study aimed to determine the relative weight of each component in contributing to optimal well-being, focusing on a Spanish population. METHODS:An observational, descriptive, cross-sectional study was conducted in Spain using best-worst scaling (BWS). Two questionnaires were developed: one addressed to patients (33 item) and the other to healthcare professionals (HCPs) (18 item). The questionnaires collected sociodemographic and clinical (patients)/occupational (HCP) characteristics of the participants and the BWS scenarios. The 20 components of well-being were randomly distributed across 76 scenarios, with each component paired with others four times to ensure a comprehensive evaluation of all possible combinations. Participants assessed 9-10 randomly selected scenarios and identified the components they considered most (best) and least (worst) important for achieving optimal well-being. RESULTS:A total of 87 HCPs and 152 patients with psoriasis participated in the study. The five key components for patients were pain (P: 100.00), stress (P: 98.74), treatment satisfaction (92.21), itching (72.05), and lesions in functional locations (P: 69.09). From a HCP perspective, the most important components were mood disorders (100.00), pain (69.39), lesions in functional locations (49.34), self-esteem (49.24), and stigmatization/shame (45.22). CONCLUSIONS:This study highlights the differences between patients and HCPs in their perception of the relative importance and relevance of the components contributing to the well-being of patients with psoriasis. Future research should focus on understanding the cumulative impact of psoriasis on patient well-being.

BACKGROUND:Psoriatic disease is a lifelong chronic illness for which there is no cure. It is well established that psoriasis leads to a major impairment of health-related quality-of-life and wellbeing. Most people with psoriasis live together with partners, bringing along a major burden for them. The FamilyPso was created to measure this burden in psoriasis. OBJECTIVE:The aim of the FamilyPso international study was to validate this tool and to show feasibility for the use of the FamilyPso across multiple countries. METHODS:A prospective cohort study was conducted in 11 centers in Austria, Canada, Germany, Italy, Spain, and Turkey. The factor structure of the FamiliyPso was examined by confirmatory factor analysis (CFA) including tests of measurement invariance for gender and language. Subgroups (e.g., countries and gender) were tested for significant differences, and the relationship between the severity of illness and FamilyPso scores was tested for differences between countries using a mixed regression model. Descriptive statistics for items and scores are presented herein. RESULTS:The cohort consisted of 556 people with psoriasis and their partners. Patients agreed that their partners would answer the questionnaire in their absence and return the forms to the centers. The mean age of patients and partners was 51 years. Psoriasis severity was mild in 57.6%, moderate in 31.5%, and severe in 10.9% of cases, and 91.3% received treatment. The results of the CFA confirmed the original factor structure with minor modifications. Self-assessed high severity of psoriasis was a predictor for a higher burden in 4/5 FamilyPso domains. There was an increased burden to partners related to the severity of psoriasis particularly in the domain "general emotional strain," including items such as a "feeling of helplessness." The results of the study showed that the FamilyPso could assess the burden of partners of people with psoriasis and can be used across different countries. CONCLUSIONS:The data can improve management of psoriatic disease and should be considered in shared decision-making.

Tildrakizumab is a monoclonal antibody targeting interleukin-23 that has gained regulatory approval for moderate-to-severe plaque psoriasis in several jurisdictions. While phase III clinical trials have evaluated its short-term efficacy and safety, real-world evidence regarding its long-term retention is limited. We report real-world drug survival of tildrakizumab in the routine clinical setting.

Background: Psoriasis is a skin disease characterized by the presence of erythematous, scaly plaques on the extensor surfaces of the body. Treatment varies according to the stage of the disease, with the most severe cases being treated with biologic treatments that differ in efficacy and persistence over time. This study aimed to evaluate the 10-year persistence of biologic drugs (adalimumab, etanercept, infliximab and ustekinumab) in the treatment of moderate-to-severe plaque psoriasis. Methods: A total of 143 patients (61 women and 82 men) were evaluated; data were collected from the electronic clinical history, and statistical analysis was performed using the SPSS program. In addition, 115 of them were genotyped in a previous study for 173 immune system genetic polymorphisms. Results: The persistence of biologic drugs at 10 years was 25.9% (95% CI: 17.2–34.5%). Adalimumab was the most persistent drug (41.5%), followed by ustekinumab (34.8%), infliximab (28%) and etanercept (9.3%). The main reason for discontinuation was insufficient efficacy (51%). Adalimumab allowed an increase in the dosing interval in 82.4% of patients who persisted and ustekinumab allowed an increase in 37.5%. The 10-year persistence was related to sex (higher in men, p < 0.001), biologic drug (p = 0.002) and polymorphisms in LMO4 (rs983332) (p = 0.014) and IL20RA (rs1167846) (p = 0.013). Conclusion: The results show that 25% of psoriasis patients treated with first-line biologics persisted at 10 years.

Galectin-1 and -9 (Gal1/9) are essential mediators of immune-inflammatory responses, which makes these proteins potential biomarkers for immune-mediated diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis (PS), psoriatic arthritis (PsA), inflammatory bowel disease, and systemic lupus erythematosus (SLE). Our aim was to evaluate plasma Gal1/9 differences between IMID patients and healthy donors (HD). We analyzed 980 plasma samples divided into two analytical cohorts (600 discovery group and 380 validation group). Generalized linear models estimated Gal1/9 levels, adjusting for sex, age, storage time, and plate variability. In the overall IMID group, plasma Gal1 levels were comparable to those of HD, while Gal9 levels were significantly elevated. Levels varied across individual diseases: SLE patients consistently showed the highest Gal1/9 levels compared to both HD and other IMIDs, and RA patients had elevated Gal9 levels versus HD. Both Gal1 and Gal9 plasma levels correlated positively with higher disease activity, and Gal1 was higher in patients with longer disease duration. After adjustment for these confounders, SLE and RA patients maintained the highest Gal9 levels compared to HD. Our study demonstrates that Gal1 and Gal9 are differentially expressed across IMIDs, with particularly elevated levels in SLE, and both galectins are associated with disease activity.

BACKGROUND:Registry studies are needed to provide comprehensive and updated assessments of the long-term safety profiles of systemic drugs in psoriasis. OBJECTIVES:To analyse the safety of biologic drugs and new oral molecules used for the treatment of moderate-to-severe psoriasis in patients included in the Spanish Registry of Adverse Events of Biological Therapy (BIOBADADERM), compared to that of adalimumab. METHODS:Prospective, multicentre cohort of patients with psoriasis. The safety profiles of biologic agents (etanercept, infliximab, adalimumab, certolizumab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab and tildrakizumab), apremilast and dimethyl fumarate were studied. The incidence rate ratio (IRR) and adjusted IRR of specific adverse events were assessed for each drug, using adalimumab as a reference. Propensity scores were used to adjust for selection bias. RESULTS:Our study included 4212 patients (7590 treatment cycles; 17,284 patient-years of follow-up). Adalimumab had an incidence rate for all adverse events of 614 per 1000 patient-years (95% confidence interval [CI] (591; 637)). The risk of all adverse events was significantly lower for guselkumab (adjusted IRR [aIRR] 0.56, 95% CI (0.47; 0.67)), risankizumab (aIRR 0.59, 95% CI (0.48; 0.71)), tildrakizumab [aIRR 0.6, 95% CI (0.46; 0.8)], ixekizumab (aIRR 0.65, 95% CI (0.56; 0.76)) and ustekinumab (aIRR 0.73 95% CI (0.65; 0.82)) compared to adalimumab (p ≤ 0.002), as well as the risk for some specific organ-based groups of adverse events. Conversely, the risk for all adverse events was significantly higher for dimethyl fumarate (aIRR 3.67, 95% CI (2.71; 4.97)), infliximab (aIRR 1.88, 95% CI (1.45; 2.43)) (p ≤ 0.002) and apremilast (aIRR 1.27, 95% CI (1.05; 1.53)) (p 0.012). The risk of malignant neoplasms was significantly reduced in the group treated with ixekizumab (aIRR 0.14 95% CI (0.04; 0.47)). CONCLUSIONS:Our data support that, overall, the new biologic treatments have a superior safety profile in real-world practice compared to adalimumab and its biosimilars.

Purpose:Psoriasis profoundly impairs patients' social, emotional, and physical condition, impacting on their overall well-being. Tildrakizumab is an interleukin-23p19 inhibitor labelled for the treatment of moderate-to-severe plaque psoriasis. The main objective of this study was to assess the effect of tildrakizumab on the overall well-being of people with psoriasis. Effectiveness, quality of life (QoL), symptomatology, treatment satisfaction, and the impact of psoriasis on the patients' partners were also evaluated. Patients and Methods:POSITIVE is a 24-month observational study in adults with moderate-to-severe psoriasis treated with tildrakizumab in a real-world setting (ClinicalTrials.gov ID: NCT04823247). Outcome measurements included the 5-item WHO Well-being Index (WHO-5), Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index-Relevant (DLQI-R), Treatment Satisfaction Questionnaire for Medication (TSQM-9), and FamilyPso. We report 52-week (W52) interim data (N = 400; observed cases). Results:Mean ± 95% CI WHO-5 score increased from 53.8 ± 2.2 at baseline to 66.0 ± 2.3/65.7 ± 2.7 at W28/W52 (p < 0.0001, both). Mean ± 95% CI PASI decreased from 13.1 ± 0.8 at baseline to 1.7 ± 0.3/1.5 ± 0.3 at W28/W52 (p < 0.0001, both). At W28 and W52, 85.8%/54.8% and 88.4%/56.8% of patients achieved PASI ≤ 3/≤ 1. Mean ± 95% CI DLQI-R score decreased from 12.6 ± 0.8 at baseline to 3.3 ± 0.6/3.1 ± 0.6 at W28/W52 (p < 0.0001, both). At W52, mean ± 95% CI TSQM-9 domain scores were 77.4 ± 3.2 for effectiveness, 81.5 ± 2.6 convenience, and 81.1 ± 2.6 global satisfaction. Mean ± 95% CI total FamilyPso decreased from 1.3 ± 0.1 at baseline to 0.7 ± 0.2 at W52 (p < 0.0001). At the point of this analysis, 24.0% of patients had ≥1 adverse event (AE). Only one patient discontinued due to a treatment-related AE. Conclusion:Tildrakizumab successfully contributes to value-based long-term health care for moderate-to-severe psoriasis by increasing patient wellbeing, QoL and clinical outcomes while showing very good safety and tolerability.

Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation. To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis. This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded. A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7

Background: Scarce data related to the drug survival of biologic agents in psoriasis patients aged >= 65 years is available. Objectives: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged >= 65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. Methods: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. Results: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. Conclusion: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI <= 1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI <= 1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI <= 1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.

This consensus document analyzed the management and emotional journey of patients with GPP (generalized pustular psoriasis), and the desirable course of the disease while detecting critical points and translating them into needs and recommendations. This project was conducted in 3 phases with participation from an advisory committee (n=8), an expert panel (n=15) and patients with GPP (n=6). The patients' disease progression was heterogeneous due to disease variations, different health care models implemented and available resources, and the lack of diagnostic and treatment guidelines. A total of 45 different recommendations have been made to optimize management and address the emotional component of these patients. Five of them stand out for their impact and viability. Therefore, a roadmap of priorities has been made generally available to improve the management of patients with GPP.

TRIBUTE is a 24-week (W) open-label phase IV study to assess tildrakizumab efficacy in adults with moderate-to-severe plaque psoriasis in conditions close to clinical practice. The six-domain Medical Outcomes Study (MOS)-Sleep scale evaluates sleep problems, being the MOS-Sleep Index II a measure of sleep quality (range 0-100; 100=worse sleep problems). QoL assessments included Dermatology Life Quality Index (DLQI; range 0-30; 30=worst QoL) and Skindex-16 (range 0-100; 100=worst QoL). Patient Benefit Index (PBI) evaluates patient-relevant treatment benefits (range 0-4; 4=maximal benefit; PBI≥1=relevant benefit). Work Productivity and Activity Impairment (WPAI) questionnaire evaluates impairments in work and activities. Analyses were based on observed cases (N=177, mean age 45 years; 70% male). Mean (SD) DLQI decreased from 14.1 (7.4) to 2.0 (3.6) at W24 (DLQI 0-1: 70.4%). At baseline, mean (SD) Skindex-16 score was 68.5 (25.0) vs 14.9 (21.8) at W24. At W24, mean (SD) PBI was 3.4 (0.6) (PBI≥1: 98.7%). All WPAI scores improved at W24. At baseline, mean (SD) Sleep Index II was 39.8 (20.3) vs 28.5 (15.6) at W24. Sleep disturbance and adequacy domains, and Sleep Index II showed significant correlations with QoL and work and activities measurements (p<0.05, all). There was no significant correlation between patient-relevant treatment benefits and sleep improvement. In conditions close to real practice, tildrakizumab improved sleep quality, which was highly correlated with improvements in QoL and work productivity and activity measurements. This highlights the importance of looking beyond the skin symptoms to improve the overall well-being of psoriatic patients.

Background: Combinations of topical (TT) and biological therapies (BT) are a common thing in the routine clinical practice. However, the scientific medical literature on how TT is, actually, used after the initiation of BT is scarce, particularly in combination with anti-IL17, or anti-IL23. Objectives: To describe the frequency of the concomitant use of TT + BT at baseline and after a 6 -month course of several drugs (anti-IL17, ustekinumab, and anti-IL23). Our secondary endpoints are to describe the type of topical therapy used, compare the frequency of use of TT among the different groups of BT, describe the survival of topical therapy in these patients, and identify the factors that can impact the use or discontinuation of topical therapy in these patients (clinical response, quality of life, type of drug, etc.). Materials and methods: This was a retrospective, observational, and single -center study of patients with moderate -to -severe psoriasis treated with anti-IL17 (secukinumab, ixekizumab), anti-IL17R (brodalumab), ustekinumab, and guselkumab from January 2015 through December 2020. Results: We included a total of 138 patients. When treatment started, 82.7% were on TT (55% daily), and after 6 months, 86.6% had discontinued TT. Regarding the analysis by type of drug, at 6 months, we found that 100% of the patients with BRO had discontinued topical treatment. We did not find any significant differences in the frequency of use of TT based on the BT used during the 6 -month course of treatment. The estimated mean course of TT was 4.3 months (SD, 6.7). Also, the estimated mean course of TT was significantly shorter in the group of patients who achieved PASI100 (2.8 months vs. 8.1 months). Conclusions: In our cohort, we saw a significant decrease in the frequency of use of TT at 6 months after starting BT in the routine clinical practice. This reduction occurred earlier in patients who improved their objective clinical response and quality of life. (c) 2024 AEDV. Published by Elsevier Espan a, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BackgroundPrediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation.ObjectiveTo identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting.MethodsWe studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI <= 3 and <= 1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed.ResultsA total of 173 patients were studied at 6 months, (67% achieved absolute PASI <= 3 and 65% PASI <= 1) and 162 at 12 months (75% achieved absolute PASI <= 3 and 64% PASI <= 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI <= 3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI <= 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI <= 3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes.ConclusionWe have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.