Clinical course and disease burden of patients with generalized pustular psoriasis in Portugal: a multicenter retrospective cohort study.

OBJECTIVES: Generalized pustular psoriasis (GPP) is a rare, life-threatening skin inflammatory disorder. This study aimed to describe the disease course, treatment strategies, and healthcare utilization among patients with GPP in Portugal. METHODS: This multicentric, observational, retrospective study included consecutive adult patients with GPP undergoing a dermatology evaluation in different reporting institutions by experienced dermatologists between 2002 and 2023. RESULTS: A total of 59 patients were assessed. Most of the cohort had a previous history of plaque psoriasis (71%) and 83% presented at least one comorbidity. At the initial encounter, 64% of the cohort needed hospitalization. Systemic involvement was common, including fever (37%), and elevated white blood cell count and erythrocyte sedimentation rate/C-reactive protein (49%). Nearly, 73% of patients initiated systemic drugs, and 70% had to discontinue the first treatment. During the study, 98% of patients experienced at least one flare. At the last visit, 3.4% of patients had died, and 71.2% exhibited signs of active disease despite undergoing treatment. CONCLUSIONS: Our study demonstrates that GPP is a chronic, debilitating condition associated with systemic involvement, frequent flares, and hospitalizations, despite receiving multiple systemic treatments. Improved disease awareness and new treatments are needed to improve patient care and decrease the burden of the disease.

Burden of impaired sleep and its improvement through topical treatment in psoriasis and atopic dermatitis.

INTRODUCTION: Patients with chronic inflammatory skin diseases often suffer from sleep disturbances. However, objective data on sleep architecture, especially to evaluate potential overall influences under therapy, are lacking. PATIENTS AND METHODS: Pilot study on sleep quality changes including psoriasis and atopic dermatitis patients before and 2 weeks after intensive topical treatment. In addition to disease activity rating, patient-rated outcomes for itch severity and sleep quality and polygraphy was performed before and after topical therapy. RESULTS: 14 psoriasis, eleven atopic dermatitis patients (10 female, 15 male) with a mean age of 49 years were included. Disease activity scores (EASI and PASI) were significantly reduced with topical therapy after 2 weeks (p < 0.001). Pruritus intensity (NRS) showed a significant influence on deep sleep, which resolved after therapy. Insomnia severity significantly decreased (r > 0.50, p < 0.05) and daytime sleepiness showed a significant reduction in 40% of patients. N3 (deep sleep) and REM sleep significantly improved, showing a strong effect (r > 0.50). The apnea-hypopnea index decreased in one of four patients independent of the individual BMI. CONCLUSIONS: Through polygraphy, we demonstrated impaired sleep patterns in psoriasis and atopic dermatitis patients with itch as a relevant factor and beyond that, rapid sleep improvement under 2 weeks of topical treatment.

Tildrakizumab: the value of a personalized and flexible approach for treating moderate-to-severe plaque psoriasis in patients with high body weight or high disease burden.

INTRODUCTION: The introduction of biologics for the treatment of plaque psoriasis is one of the major therapeutic advances of the last decades in dermatology. The efficacy of this class of drugs can be influenced by multiple factors including obesity, being overweight, prior treatment failures, and disease severity. AREAS COVERED: Most of the currently available approved biologics are limited by their lack of dosing flexibility for adapting the therapy to the complexity of real-world patients with psoriasis. Among the class of anti-interleukin-23, tildrakizumab allows a greater dosing flexibility, increasing clinical benefits of patients with high burden of the disease or body weight >90 kg. EXPERT OPINION: This meta-opinion discusses the clinical data that were foundational for tildrakizumab dosage flexibility, elaborates on the definition of high burden of disease specifically linked to tildrakizumab dosage, and profiles the ideal patient that could benefit from treatment with the higher approved tildrakizumab dosage of 200 mg.

[Translated article] Approach to the Epidemiology, Disease Management, and Current Challenges in the Management of Generalized Pustular Psoriasis Through a Survey Conducted Among Spanish Dermatologists.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease characterised by recurrent or intermittent flares. Epidemiological and disease management data in Spain are limited. Our goal was to estimate the epidemiology of GPP, explore its management, and reach consensus on the current challenges faced in Spain. METHODS: An electronic survey was submitted to dermatologists from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group. This group is experienced in the management of GPP. It included a Delphi consensus to establish the current challenges. RESULTS: A total of 33 dermatologists responded to the survey. A 5-year prevalence and incidence of 13.05 and 7.01 cases per million inhabitants, respectively, were estimated. According to respondents, the most common GPP symptoms are pustules, erythema, and desquamation, while 45% of patients present > 1 annual flares. A total of 45% of respondents indicated that flares often require a length of stay between 1 and 2 weeks. In the presence of a flare, 67% of respondents often or always prescribe a non-biological systemic treatment as the first-line therapy [cyclosporine (55%); oral retinoid (30%)], and 45% a biological treatment [anti-TNFα (52%); anti-IL-17 (39%)]. The dermatologists agreed that the main challenges are to define and establish specific therapeutic goals to treat the disease including the patients' perspective on the management of the disease. CONCLUSION: Our study describes the current situation on the management of GPP in Spain, increasing the present knowledge on the disease, and highlighting the current challenges faced at the moment.

Real-world biologic treatment patterns and healthcare resource utilization in psoriasis patients using an insurance claims database in Japan.

BACKGROUND: With advent of newer treatments for psoriasis, real-world use of biologics in Japan is evolving. METHODS: This retrospective study utilized data from patients with ≥1 psoriasis-related biologic claims record between January 2016 and December 2020 in Japan to evaluate treatment patterns, healthcare resource utilization (HCRU), and associated costs. Data were analyzed using descriptive statistics. RESULTS: Of 1,614 eligible patients, 72.5% were male, 29.2% had comorbid hypertension and 26.6% had comorbid cardiovascular disease. Interleukin (IL)-17 and tumor necrosis factor alpha (TNFα) inhibitors were commonly prescribed across lines of treatment, while IL-23 inhibitors were most considered for switches (92% of switches were from IL-12/23/IL-17/TNFα inhibitors). The overall mean adherence rate for all classes was 80.1%, but adherence varied across biologics. Infliximab and IL-23 inhibitor users exhibited optimal medical possession ratios, reflecting the best adherence rates. Overall HCRU (visits/patient-year) was 9.05 for outpatient visits, 0.09 for inpatient hospitalization, and 0.5 for psoriasis-related phototherapy. HCRU associated with hospitalization was slightly higher for bio-experienced patients and so was the overall costs per patient-year relative to bio-naïve patients. CONCLUSION: Variable adherence rates observed suggest the need for improvement in treatment management with different biologics. Bio-experienced patients burdened by disease progression and treatment switches may result in increased HCRU.

Reduced economic disparity in biologics use for psoriasis after introducing the reducing copayment program.

Biologics for psoriasis are efficient and safe, but very expensive. We investigated the association of the reducing copayment program (RCP) with changes in biologics use patterns depending on the income levels of patients with moderate-to-severe psoriasis. This nationwide cohort study included patients identified as having moderate-to-severe psoriasis between 2014 and 2020. Logistic regression models were used to estimate the odds ratio for the use of biologics according to income levels. Among 57,139 patients with moderate-to-severe psoriasis, 3464 (6.1%) used biologics for psoriasis from 2014 to 2020. After the introduction of RCP in 2017, the proportion of patients with moderate-to-severe psoriasis using biologics rapidly increased from 5.0% in 2016 to 19.2% in 2020; the increase was more remarkable in patients with the lowest or mid-low income compared to those with Medical Aid. Drug survival of biologics was higher in patients with the highest income before the RCP, but became comparable between those with high and low incomes after RCP introduction. The introduction of RCP was associated with an increased use of biologics in patients with moderate-to-severe psoriasis of all income levels; however, the effect was more pronounced in low-income patients. The RCP may contribute to alleviating the disparity in access to biologics.

Use of Efficiency Frontiers to Align Prices and Clinical Benefits of Biologic Therapies for Plaque Psoriasis.

Importance: The US lacks a systematic approach for aligning drug prices with clinical benefit, and traditional cost-effectiveness analysis (CEA) faces political obstacles. The efficiency frontier (EF) method offers policymakers an alternative approach. Objective: To assess how the EF approach could align prices and clinical benefits of biologic medications for plaque psoriasis and estimate price reductions in the US vs 4 peer countries: Australia, Canada, France, and Germany. Design and Setting: This health economic evaluation used the EF approach to compare the prices and clinical benefits of 11 biologics and 2 biosimilars for plaque psoriasis in the US, Australia, Canada, France, and Germany. Data were collected from February to March 2023 and analyzed from March to June 2023. Main Outcome Measures: EFs were constructed based on each biologic's efficacy, measured using the Psoriasis Area and Severity Index (PASI) 90 response rate, and annual treatment cost as of January 2023; US costs were net of estimated manufacturer rebates. Prices based on the EF were compared with traditional CEA-based prices calculated by the Institute for Clinical and Economic Review at a threshold of $150 000 per quality-adjusted life-year gained. Results: Among 13 biologics, PASI 90 response rates ranged from 17.9% (etanercept) to 71.6% (risankizumab); US net annual treatment costs ranged from $1664 (infliximab-dyyb) to $79 277 (risankizumab). The median (IQR) net annual treatment cost was higher in the US ($34 965 [$20 493-$48 942]) than prerebate costs in Australia ($9179 [$6691-$12 688]), Canada ($15 556 [$13 017-$16 112]), France ($9478 [$6637-$11 678]), and Germany ($13 829 [$13 231-$15 837]). The US EF included infliximab-dyyb (PASI 90: 57.4%; annual cost: $1664), ixekizumab (PASI 90: 70.8%; annual cost: $33 004), and risankizumab (PASI 90: 71.6%; annual cost: $79 277). US prices for psoriasis biologics would need to be reduced by a median (IQR) of 71% (31%-95%) to align with those estimated using the EF; the same approach would yield smaller price reductions in Canada (41% [6%-57%]), Australia (36% [0%-65%]), France (19% [0%-67%]), and Germany (11% [8%-26%]). Except for risankizumab, the EF-based prices were lower than the prices based on traditional CEA. Conclusions and Relevance: This economic evaluation showed that for plaque psoriasis biologics, using an EF approach to negotiate prices could lead to substantial price reductions and better align prices with clinical benefits. US policymakers might consider using EFs to achieve prices commensurate with comparative clinical benefits, particularly for drug classes with multiple therapeutic alternatives for which differences can be adequately summarized by a single outcome measurement.

Assessment of safety profile of secukinumab in real-world scenario using United States food and drug administration adverse event reporting system database.

Secukinumab is an anti-IL-17 monoclonal antibody approved for treating psoriasis and various arthritides. A comprehensive evaluation of its safety, especially in a real-world setting, is necessary. This study aimed to describe the adverse events (AE) associated with secukinumab use using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. FAERS data files containing AE reports from 2015 to 2021 were downloaded for data mining. Primary or secondary suspect medications indicated for psoriasis were identified and analyzed. Medical dictionary for regulatory activities (MedDRA version 24.1) was used to analyze the AE terms. To detect potential safety signals of AE from secukinumab use, disproportionality analysis was used. A total of 365,590 adverse event reports were identified; of these, 44,761 reports involved the use of secukinumab. Safety signals were identified for ocular infections and gastrointestinal adverse events at the standardised MedDRA query level. Safety signals for oral candidiasis, oral herpes, conjunctivitis, eye infections, and ulcerative colitis were identified at the preferred term level. The findings of our study are consistent with those of earlier studies, such as the increased risk of infections and inflammatory bowel disease. However, our study also identified additional safety signals that need to be further evaluated.

Non-Invasive Assessment of Skin Surface Proteins of Psoriasis Vulgaris Patients in Response to Biological Therapy.

Measurements of skin surface biomarkers have enormous value for the detailed assessment of skin conditions, both for clinical application and in skin care. The main goals of the current study were to assess whether expression patterns of skin surface hBD-1, hBD-2, IL-1α, CXCL-1, and CXCL-8, examples of proteins known to be involved in psoriasis pathology, are associated with disease severity and whether expression patterns of these proteins on the skin surface can be used to measure pharmacodynamic effects of biological therapy. In this observational study using transdermal analysis patch (TAP), levels of skin surface IL-1α, hBD-1, hBD-2, CXCL-1/2, and CXCL-8 of psoriasis vulgaris (PV) patients over biological therapy were assessed. The Psoriasis Area Severity Index (PASI) and local score for erythema, induration, and desquamation were determined from the exact same skin area as FibroTx TAP measurements. Thirty-seven adult PV patients were included, of which twenty-three were subjected to anti-TNF-α, seven to anti-IL-17A, and seven to anti-IL12/IL-23 therapy. Significantly higher levels of hBD-1, hBD-2, CXCL-1/2, and CXCL-8 were detected on lesional skin compared to the non-lesional skin of the PV patients. In contrast, lower levels of IL-1α were found in lesional skin compared to non-lesional skin. In addition, we observed that the biomarker expression levels correlate with disease severity. Further, we confirmed that changes in the expression levels of skin surface biomarkers during biological therapy correlate with treatment response. Biomarker expression patterns in response to treatment differed somewhat between treatment subtypes. We observed that, in the case of anti-TNF-α therapy, an increase after a steady decrease in the expression levels of CXCL-1/2 and CXCL-8 occurred before the change in clinical scores. Moreover, response kinetics of skin surface proteins differs between the applied therapies-hBD2 expression responds quickly to anti-IL-17A therapy, CXCL-1/2 to anti-IL-12/23, and levels of CXCL-8 are rapidly down-regulated by IL-17A and IL-12/23 therapy. Our findings confirm that the skin surface hBD-2, IL-1α, CXCL-1/2, and CXCL-8 are markers for the psoriasis severity. Further, data obtained during this study give the basis for the conclusion that skin surface proteins CXCL-1/2 and CXCL-8 may have value as therapeutic biomarkers, thus confirming that measuring the 'molecular root' of inflammation appears to have value in scoring disease severity on its own.

Drug utilization and medical expenses in psoriasis treatment at a dermatology hospital in Vietnam, 2019-2021.

Introduction: Psoriasis is a persistent, chronic, inflammatory cutaneous disorder that recurs frequently and has negative impacts on the living quality of sufferers. Methods: Data from the Inpatient and Outpatient Department medical records at Can Tho dermatology hospital were used to generate a descriptive statistics report on medicines and medical costs for psoriasis therapy in 2019-2021. Results: The average number of prescription medications varied annually, averaging roughly 0.62±85.4% per prescription. Corticosteroids and calcipotriol were the most commonly recommended drugs for psoriasis. Antihistamines were the most often used medication, with over 12,000 instances among the 28,397 individuals studied. The peak in average per-treatment expenses occurred in 2021 when they fluctuated between US $120 and US $160. In contrast, examination expenses were the most costly, ranging from US $93-$107. Conclusion: The bulk of psoriasis therapy treatments were topical agents, whose quantities rose progressively. Direct examination expenses accounted for the greatest proportion.

Individual Article: Brodalumab Is an Efficacious, Safe, and Cost-Effective IL-17 Receptor Blocker for the Treatment of Moderate-to-Severe Plaque Psoriasis: 2023 Update.

Psoriasis remains a highly prevalent condition in the United States and worldwide. Preclinical research has been triumphant in elucidating the critical immunological pathways involved in psoriasis. There has been an evolution in biologics that paralleled the understanding of these pathways beginning with anti-tumor necrosis factor (TNF) inhibitors and now most recently the interleukin (IL)-23 and IL-17 axes. Numerous evidence-based studies demonstrate the efficacy of these agents for skin clearance in moderate-to-severe plaque psoriasis. Brodalumab, a fully humanized IL-17 receptor A (IL-17RA) antagonist, is wholly unique in that it binds to a cytokine receptor and not a cytokine itself unlike the other biologics indicated for psoriasis. This unique mechanism has lent an advantage where not only is brodalumab effective in treating moderate-to-severe plaque psoriasis, but it is also successful in psoriasis patients whose disease did not respond to other biologics. This review provides a summary of the efficacy of brodalumab in plaque psoriasis and difficult-to-treat locations (ie, scalp, nail, palmoplantar), in patients with psoriasis who failed to achieve minimum clearance with other biologics, and it illuminates the most recent pharmacovigilance data obtained from the past 5 years. Furthermore, the cost effectiveness of brodalumab is also discussed. J Drugs Dermatol. 2023;22:10(Suppl 1):s5-14.

Comparison of a second TNFi vs other biologic or targeted synthetic DMARD following an initial TNFi.

BACKGROUND: Patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis may require treatment with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Often, a tumor necrosis factor inhibitor (TNFi) is the initial b/tsDMARD. The TNFi may not be effective or may not be well tolerated, so patients will opt for a different TNFi or switch to a non-TNFi b/tsDMARD. No preference for a TNFi or non-TNFi has been established and guidelines are unclear. OBJECTIVE: To evaluate effectiveness by comparing patients using a second TNFi vs a non-TNFi after initial use of TNFi based on treatment patterns and health care utilization. METHODS: This retrospective analysis used Medicare Advantage prescription drug (MAPD) plan, Medicaid, and commercial plan claims data from Humana's Research Database (Louisville, KY). The first claim for TNFi or non-TNFi (July 1, 2016, to June 30, 2018) following earlier TNFi was the index date. Patients were required to have pre-index enrollment of 6 months and 12 months post-index along with diagnosis of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, or psoriasis. During the 12-month follow-up, persistence to the index TNFi or non-TNFi was measured as continued therapy without a gap exceeding 45 days (81 days for intravenous infusions). Adherence was proportion of days covered at least 0.8. Addition of a nonbiologic DMARD or corticosteroid was also identified. Inpatient admissions and emergency department visits were observed. Inverse probability of treatment weights was used to balance cohorts. Logistic regression models were fit to TNFi vs non-TNFI on treatment and utilization measures. RESULTS: Of identified patients, 1,022 were indexed to a second TNFi and 1,024 were indexed to non-TNFi. Weighted cohorts were balanced, with mean age 56.5 vs 56.4 years, 70.5% vs 70.7% female sex, and 68.0% vs 67.9% MAPD plan. No differences were observed on persistence or adherence, with adjusted odds ratios (OR) of 1.05 (95% CI = 0.91-1.20) and 1.04 (0.91-1.20), respectively. No differences were observed for changes in therapy via switching to another TNFi/non-TNFi (OR = 0.93; 95% CI = 0.54-1.62), via nonbiologic DMARD addition (OR = 0.95; 95% CI = 0.83-1.11), or corticosteroid addition (OR = 1.09; 95% CI = 0.92-1.88). No differences were observed for hospitalization (OR = 1.16; 95% CI = 0.99-1.37) or emergency department visits (OR = 1.02; 95% CI = 0.89-1.18). CONCLUSIONS: No differences were found between a second TNFi vs a non-TNFi. As a result, choice of TNFi or non-TNFi following an initial TNFi may be driven by relevant patient-specific considerations. At the population level, policies that prefer either TNFi or non-TNFi appear reasonable. DISCLOSURES: The study was funded by Humana Inc. Mr Racsa is an employee of Humana Healthcare Research, Inc., a subsidiary of Humana Inc. Drs Asante and Bloomfield are employees of Humana Inc. Dr Schwab was an employee of Humana Healthcare Research, Inc., a subsidiary of Humana Inc., and is now an employee of RTI Health Solutions. Dr Cornett was an employee of Humana Inc. and is now an employee of ImmunoGen Inc.

Determining patient value profiles in psoriasis.

BACKGROUND: Healthcare professionals (HCPs) should strive to create the maximum value for their patients in which value is defined as the patient-relevant health outcomes achieved per costs made. However, currently it remains difficult to determine which outcomes matter to an individual psoriasis patient. OBJECTIVE: To define outcome profiles, or so called 'patient value profiles', within a cohort of psoriasis patients that can be translated to daily practice to increase value for the individual patient. METHODS: Hierarchical clustering on principal components (HCPC) was used to identify groups of patients sharing the same profile within an outcome ranking exercise. Once the clusters were defined, their characterization was provided based on a V-test. In a final step, a multi-class decision tree (MDT) based on relevant socio-demographic and clinical variables was built to allocate patients to a cluster. RESULTS: In the ranking exercise 120 patients participated. The median age was 50.0 (IQR 25.0) years and 36.7% were female. Median PASI score was 2.4 (IQR 5.2) and median duration of psoriasis was 17.0 (IQR 20.0) years. Primary treatment varied from topicals to biologicals. We found three distinct patient value profiles in this cohort (QoL, cost and treatment). A MDT was built which had an accuracy of 64%. CONCLUSION: We found three distinct patient value profiles in a cohort of psoriasis patients and patients can be easily assigned to one of these profiles based on a MDT. HCPs can use these profiles to steer psoriasis management accordingly allowing for a more goal-orientated approach.

The economic burden and quality of life of patients with psoriasis treated with biologics in China.

BACKGROUND: Although biologics improve the quality of life of psoriasis patients, they also impose a substantial economic burden. There is a lack of research addressing the economic and humanistic impact of biologics in China. OBJECTIVE: This cross-sectional investigation aims to assess the economic cost, quality of life, and patient satisfaction among individuals with psoriasis treated with biologics and non-biologics. METHODS: From July 2021 to December 2022, eligible patients with psoriasis were recruited through both on-site and online questionnaire completion. The questionnaires collected sociodemographic data, clinical characteristics of psoriasis, economic costs associated with treatment, and the Dermatological Life Quality Index (DLQI). RESULTS: 481 patients with a mean age of 40.8 ± 13.4 years old were included and classified into a non-biologic (n = 195) and biologic (n = 286) treatment group. The direct medical cost for non-biologics patients was 7,249 CNY, accounting for 70.0% of the total cost, while biologics patients incurred 15,176 CNY, making up 94.3% of the total cost. The non-biologic group had higher costs related to hospitalization, self-purchase of drugs, and indirect costs than the biologic treatment group. Additionally, DLQI scores were higher in the non-biologic group. CONCLUSION: Patients in the biologic group experienced a higher economic burden and better quality of life than those in the non-biologic group.

An Assessment of Comparative Medication Durability in Inflammatory Bowel Disease Patients With and Without Co-morbid Psoriasis, Rheumatoid Arthritis, and/or Enteropathic Arthritis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk for many co-morbid diseases. However, little is known about durability of IBD medications in patients with co-morbid diseases. AIMS: Determine medication durability in IBD patients with and without psoriasis, rheumatoid arthritis, and/or enteropathic arthropathy. METHODS: All patients with at least three ICD-9 or 10 diagnoses for IBD were included in the cohort. The risk factors of interest were a co-morbid diagnosis of psoriasis (IBD-Ps), rheumatoid arthritis (IBD-RA), and/or enteropathic arthritis (IBD-EA). Medication durability was defined as days of medication use, calculated using order start and stop dates from the electronic medical record. Significant differences were tested using the Wilcoxon rank sum test for continuous variables and Fisher's exact test or Pearson's Chi-squared test, as appropriate, for categorical variables. Boxplots were constructed for graphical interpretation of results. RESULTS: In the psoriasis group, there were 481 patients with 831 medication exposures [131 IBS-Ps (16%), 700 IBD only (84%)]. The median days of medication use were numerically higher in the IBD-Ps group for all therapies [anti-TNF: 1109 vs 861 (p = 0.17); anti-IL-12/23: 984 vs 834 (p = 0.33); JAKi: 682 vs 230 (p = 0.13)], anti-TNF/IM: 370 vs 202 (p = 0.57), except anti-integrin therapy [214 vs 470 (p = 0.08)]. When restricting to UC only, patients with co-morbid again Ps had a significantly shorter duration on anti-integrin therapy (84 vs 456 days, p = 0.02). While not reaching statistical significance, there was a distinctly longer medication duration on JAKi therapy (910 vs 317, p = 0.10). When restricting to patients with CD only, no results reached statistical significance though there was a trend towards longer anti-TNF durability in CD-Ps (1340 vs 1000 days, p = 0.098). There were no differences in medication durability in IBD-RA or IBD-EA patients. DISCUSSION: Larger studies investigating medication durability of JAKi and anti-integrin therapy in IBD patients with psoriasis would be beneficial given noteworthy trends towards increased and decreased durability, respectively.