Long-term quality of life outcomes from a phase 4 study of tildrakizumab in patients with moderate-to-severe plaque psoriasis in a real-world setting.

BACKGROUND: Tildrakizumab is an anti-interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. This report describes final primary results of a 64-week real-world study of the effect of tildrakizumab on patients' health-related quality of life (HRQoL). MATERIALS AND METHODS: In this open-label phase 4 study (NCT03718299), patients with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at week 0, week 4, and every 12 weeks thereafter through week 52. The primary endpoint was improvement from baseline in HRQoL measured by Psychological General Well-Being Index (PGWBI) total score at weeks 28 and 52. Secondary HRQoL endpoints included change from baseline in Dermatology Life Quality Index (DLQI) score through week 64. Missing data were not imputed. RESULTS: Of 55 patients enrolled, 45 were assessed at week 64. Mean ± standard deviation (SD) total PGWBI score improved from 78.1 ± 14.1 at baseline to 85.2 ± 12.0 at week 52 (p < .001). Mean ± SD DLQI score improved from 9.4 ± 5.2 at baseline to 2.0 ± 2.6 (p < .001) at week 64 with 62.2% of patients having a DLQI score of 0 or 1 at week 64. CONCLUSIONS: Tildrakizumab improved long-term HRQoL in patients with psoriasis in a real-world setting.

Psoriasis and Sleep Disturbance: A US Population-Based Study Using the NHANES Database.

INTRODUCTION: Psoriasis, a chronic inflammatory skin condition, affects approximately 3.0% of the US population, with patients often experiencing significant sleep disturbances. These disturbances include a higher prevalence of conditions such as obstructive sleep apnea, restless leg syndrome, and insomnia. Given the additional risks for cardiovascular disease, metabolic disorders, and depression linked to both poor sleep and psoriasis, addressing sleep issues in this patient group is critical. METHODS: The study utilized National Health and Nutrition Examination Survey (NHANES) data, focusing on individuals aged ≥ 20 years who provided information on psoriasis status and sleep. Multistage stratified survey methodology was applied, with multivariable logistic regression models used to examine the association between psoriasis and sleep issues, adjusting for factors such as age, gender, and health history. RESULTS: Psoriasis diagnosis was significantly associated with trouble sleeping (adjusted odds ratio [aOR] 1.88; 95% confidence interval [CI] 1.44-2.45). There was no significant association between psoriasis and sleep quantity. Older age, female gender, and a history of sleep disorders were predictors of trouble sleeping among psoriasis patients. CONCLUSIONS: Psoriasis is significantly associated with sleep disturbances, independent of sleep duration. This underscores the need for clinical screening focusing on sleep quality rather than quantity in psoriasis patients to effectively identify and treat sleep-related comorbidities. Further research using objective sleep measures is warranted to guide clinical management and improve patient quality of life.

Evaluating prevalence and consequence of residual disease in individuals with psoriasis receiving apremilast treatment: results from a US patient survey.

Purpose: This noninterventional, cross-sectional survey estimated the prevalence and consequences of residual disease in apremilast-treated US adults with moderate to severe psoriasis. Materials and Methods: Residual disease was defined as experiencing moderate, severe, or very severe psoriasis over the past week or having ≥3% body surface area affected, despite treatment. Factors associated with residual disease and its effects on flare-ups, humanistic burden, and health care resource utilization (HCRU) were evaluated. Results: Of the 344 apremilast users (mean age, 44.9 years; female, 65.4%), 174 (50.6%) had residual disease. It was more prevalent in Black versus White participants (OR, 4.5; 95% CI, 1.6-12.2), those receiving apremilast for ≥1 versus <1 year (OR, 16.5; 95% CI, 7.9-34.4), those reporting ≥2 versus 0 to 1 flare-ups during the past 3 months (OR, 10.0; 95% CI, 5.0-20.1), and those with ≥4 versus 1 to 3 body regions affected at time of survey (OR, 8.6; 95% CI, 3.8-19.8). Participants with versus without residual disease self-reported more psoriasis flare-ups over the past 3 months (mean, 4.7 vs 0.9; p < .001) and more anxiety (89.7% vs 50.0%; p < .001) and depression (69.0% vs 23.6%; p < .001) over the past 30 days. Conclusion: Generally, participants with versus without residual disease also had significantly more comorbidities and greater HCRU.

Improvements in Psoriasis-Related Work Productivity with Tildrakizumab: Results from a Phase 4 Real-World Study in Patients with Moderate-to-Severe Plaque Psoriasis.

INTRODUCTION: Plaque psoriasis is a chronic condition that may impact patients' work productivity. Tildrakizumab, an interleukin-23 p19 inhibitor, is approved for treatment of moderate-to-severe plaque psoriasis in adults. However, the effect of tildrakizumab treatment on work productivity in patients with psoriasis is not well characterized. METHODS: In this multicenter, open-label, uncontrolled phase 4 study (NCT03718299), patients with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at week 0, week 4, and every 12 weeks thereafter through week 52. Patients completed the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI:PSO) at baseline and every 12 weeks from week 16 through week 64. The following four domains of the WPAI:PSO were examined: absenteeism (percentage of time missed from work due to psoriasis), presenteeism (percentage reduction of productivity while at work due to psoriasis), total activity impairment (percentage impairment in activities other than work due to psoriasis), and total work productivity impairment (total percentage of work impairment from both absenteeism and presenteeism due to psoriasis). Missing data were not imputed. RESULTS: Of the 55 patients enrolled, 31 patients completed all domains of the WPAI:PSO at week 64. From baseline to week 64, respectively, mean ± standard deviation (SD) scores improved for presenteeism (20.5 ± 21.7 to 2.6 ± 5.8; P < 0.001), total activity impairment (29.5 ± 26.6 to 4.4 ± 9.4; P < 0.001), and total work productivity impairment (20.9 ± 22.2 to 2.6 ± 5.8; P < 0.001). The mean ± SD score for absenteeism decreased from 1.1 ± 5.7 at baseline to 0.0 ± 0.0 at week 64, but this change was not statistically significant. CONCLUSION: Tildrakizumab treatment mitigated work productivity loss due to psoriasis as measured by the presenteeism, total activity impairment, and total work productivity impairment domains of the WPAI:PSO. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03718299.

Clinical and Disease Burden of Patients with Generalized Pustular Psoriasis: A Review of Real-World Evidence.

Generalized pustular psoriasis (GPP) is a chronic, rare, and potentially life-threatening disease. There is limited understanding of patient characteristics in GPP and their correlation with disease progression or healthcare resource utilization. Our review aims to examine real-world evidence on these characteristics and the associated disease burden as related to economic and quality of life factors. Results showed that most patients with GPP experienced flares once a year, lasting from 2 weeks to 3 months, with > 80% of patients having residual disease post-flare, with/without treatment, indicating the long-term nature of GPP. The impact of GPP on patients' daily activities was significant, even in the absence of a flare. GPP adversely affected mental health, and anxiety and depression were reported regularly. Patients with GPP had more comorbidities, were prescribed more medication, and had more inpatient and outpatient visits than in matched plaque psoriasis or general population cohorts. Improving the education of healthcare providers in diagnosing GPP, defining disease flares, and managing the disease, as well as making globally accepted clinical guidelines for GPP treatment available, could help to reduce the burden on patients with GPP. Effective therapies that control and prevent GPP flares and manage chronic disease are needed.

A single-cell atlas of IL-23 inhibition in cutaneous psoriasis distinguishes clinical response.

Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of interleukin-23 (IL-23) signaling, but the genetic mechanisms underlying clinical responses remain poorly understood. Using single-cell transcriptomics, we profiled immune cells isolated from lesional psoriatic skin before and during IL-23 blockade. In clinically responsive patients, a psoriatic transcriptional signature in skin-resident memory T cells was strongly attenuated. In contrast, poorly responsive patients were distinguished by persistent activation of IL-17-producing T (T17) cells, a mechanism distinct from alternative cytokine signaling or resistance isolated to epidermal keratinocytes. Even in IL-23 blockade-responsive patients, we detected a recurring set of recalcitrant, disease-specific transcriptional abnormalities. This irreversible immunological state may necessitate ongoing IL-23 inhibition. Spatial transcriptomic analyses also suggested that successful IL-23 blockade requires dampening of >90% of IL-17-induced response in lymphocyte-adjacent keratinocytes, an unexpectedly high threshold. Collectively, our data establish a patient-level paradigm for dissecting responses to immunomodulatory treatments.

Risk of Cutaneous T Cell Lymphoma with Psoriasis Biologic Therapies.

BACKGROUND: The risk of developing cutaneous T cell lymphoma (CTCL) in patients using psoriasis biologics has not been well characterized. The goals of this review were to investigate the incidence of CTCL in patients with psoriasis receiving biologic therapy in clinical trials and psoriasis registries, and to review cases of CTCL and biologic use reported in scientific publications. METHODS: The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify phase 3 and 4 clinical trials of the 12 biologic agents currently FDA approved for psoriatic disease. The incidence of CTCL in these trials was examined and summarized. To examine the incidence of CTCL in psoriasis registries, a Medline search was conducted. Finally, we performed a systematic review of CTCL cases reported in the literature. RESULTS: Only two cases of CTCL were reported in 35,801 subjects with psoriasis receiving a biologic agent in the active arm of 108 psoriasis phase 3 clinical trials. One of these CTCL cases was determined by the investigator to be CTCL misdiagnosed as psoriasis prior to randomization. No cases of CTCL were reported in 5440 subjects with psoriasis in 34 phase 4 clinical trials. Only one case of CTCL was identified in 34,111 registry subjects. In the literature, tumor necrosis factor (TNF) inhibitors had the highest number of reported cases of CTCL (34 cases), followed by interleukin (IL)-17 inhibitors (7 cases), and IL-12/23 inhibitors (6 cases). No cases of CTCL were found to be reported with IL-23 inhibitors. CONCLUSION: Our findings indicate that the development of CTCL is rare in the setting of psoriasis biologic use. Of the limited number of cases of CTCL found, most were in the setting of TNF inhibitor use and no cases of CTCL were reported in the setting of IL-23 inhibitor use.

Current practices for pediatric phototherapy: Findings from a cross-sectional study.

Phototherapy is broadly utilized for treatment of inflammatory skin conditions affecting pediatric patients. However, there are no specific guidelines or recommendations for implementing phototherapy in pediatric populations leading to variability in treatment procedures. Here, we present findings from a cross-sectional, survey-based study investigating the implementation of phototherapy in pediatric patients across the United States. A total of 39 sites from 19 different states identified via the National Psoriasis Foundation (NPF) Health Care Provider Directory responded. Common practices included a signed informed consent prior to performing phototherapy (86.4%, n = 32), no minimum age requirement for pediatric patients (91.8%, n = 34), the use of Fitzpatrick skin type to determine dosing protocol (100%, n = 37), and allowing parents to accompany their children into the lightbox (65%, n = 20). Our results provide insights into current common practices and themes for further study.

Mendelian Randomization Studies in Atopic Dermatitis: A Systematic Review.

Prior studies have found associations between atopic dermatitis (AD) and comorbidities, including depression, obesity, asthma, and allergic rhinitis. Although observational studies often cannot establish robust causality between potential risk factors and AD, Mendelian randomization minimizes confounding when exploring causality by relying on random allelic assortment at birth. In this study, we systematically reviewed 30 Mendelian randomization studies in AD. Body mass index, gut microbial flora, the IL-18 signaling pathway, and gastroesophageal reflux disease were among the causal factors for AD, whereas AD was causal for several medical conditions, including heart failure, rheumatoid arthritis, and conjunctivitis. These insights may improve preventive counseling in AD.

Exploring the Quality-of-Life Impact, Disease Burden, and Management Challenges of GPP: The Provider and Patient Perspective [Podcast].

Generalized pustular psoriasis (GPP) is a rare, chronic, and debilitating disease characterized by flares of widespread erythema, desquamation, and pustule formation. GPP flares can be accompanied by systemic symptoms including fever, fatigue, malaise, and skin pain; severe cases may be fatal if untreated. Although GPP may occur concurrently with plaque psoriasis, they represent two distinct inflammatory conditions. Patients with GPP experience a substantial burden of disease, and the impact of GPP on an individual's mental health and quality-of-life (QoL) goes far beyond skin pain and discomfort. The rarity of GPP may result in a misdiagnosis, as the sudden onset of skin pustules may be mistaken for a primary infection. Misdiagnosis with a subsequent delay in treatment has tremendous negative consequences for the affected patient. In September 2022, spesolimab became the first FDA-approved medication in the US for the treatment of GPP flares in adults. Spesolimab has since been approved by regulatory agencies in numerous countries, including Japan, Mainland China, and the EU. Prior to spesolimab, the clinical management of GPP relied on the off-label use of systemic or biologic therapies approved for plaque psoriasis or other inflammatory conditions. There is a need for increased education among healthcare providers regarding the clinical diagnosis, risk stratification, and therapeutic management of this rare disease, including the other novel GPP-specific therapies in development. In this podcast, two dermatologists and a patient who has plaque psoriasis and GPP discuss the clinical presentation, symptoms, disease burden, QoL impacts, diagnostic challenges, and therapeutic strategies for the management of GPP.

Association Between Poor Sleep and Myocardial Infarction in Patients with Psoriasis: Findings from a Cross-Sectional Study with the National Psoriasis Foundation.

BACKGROUND: Poor sleep quality occurs in patients with psoriasis at rates nearly twice that of the general population. Chronic sleep impairment is an independent risk factor for the development of cardiovascular disease. Here, we examine the association between sleep quantity and history of myocardial infarction in patients with psoriasis. METHODS: This observational, cross-sectional study utilized data from the 2020 National Psoriasis Foundation Annual Survey. Effect estimates were obtained using a multivariate logistic regression model, which controlled for prespecified covariates. RESULTS: Based on data from 1405 individuals with psoriasis, our analysis demonstrated a significant association between sleep quantity and history of myocardial infarction: odds ratio (OR) 0.67 [95% confidence interval (CI) 0.49-0.92], p = 0.012. The association was not significantly influenced by psoriasis severity (OR 1.01, [95% CI 0.99-1.03], p = 0.38), comorbid psoriatic arthritis (OR 1.06, [95% CI 0.48-2.38], p = 0.88), sleep apnea, or other traditional risk factors for myocardial infarction. CONCLUSION: Our analyses indicate an association between sleep quantity and history of myocardial infarction in patients with psoriasis. For each hour increase in average nightly sleep, patients with psoriasis have a 33% decrease in the odds of having a history of myocardial infarction. The chief limitation of this study is its cross-sectional design limiting ascertainment of causality.

Management of Plaque Psoriasis in Adults: Clinical Utility of Tapinarof Cream.

Topical medications represent the most commonly used drugs in the treatment of psoriasis. However, topical steroids are mainly limited to short-term or intermittent use, and traditional non-steroidal topicals such as vitamin D analogues, topical calcineurin inhibitors, and topical retinoids are limited by low efficacy and poor local skin tolerability. Tapinarof (GSK2894512, DMVT-505) is a novel, topical aryl hydrocarbon receptor (AHR) agonist, which was recently approved by the FDA for the treatment of plaque psoriasis in adults. Tapinarof acts to improve psoriasis through diminished IL-17A production by CD4+ T cells, increased barrier gene expression in keratinocytes, and reduced production of reactive oxygen species. Both short-term and long-term efficacy and safety have been evaluated in two Phase II and two Phase III (PSOARING 1 and 2) clinical trials in addition to a long-term extension study (PSOARING 3). Overall, the drug has shown beneficial effects in achieving clear skin in adults with moderate-to-severe psoriasis, good local tolerability, and also a long duration of effect even after discontinuation of the drug. Therefore, this therapy provides a new, highly effective and safe non-steroidal option to add to our psoriasis treatment toolbox for both initial clearance and long-term maintenance of disease.

Rapid Remission of Sunburn-Induced Guttate Psoriasis with Guselkumab.

Guselkumab is an anti-interleukin-23 monoclonal antibody that is approved for plaque psoriasis and psoriatic arthritis. We present a case of a 28-year-old female patient with acute onset of guttate psoriasis after a blistering sunburn. She had no personal or family history of psoriasis or chronic inflammatory skin disease. The guttate psoriasis was refractory to topical treatment. After the first dose of guselkumab (100 mg subcutaneous injection), the patient experienced near-clearance of her guttate psoriasis, with continued improvement and drug-free remission 8 months after cessation of treatment. Dermatologists could consider guselkumab as a treatment option for patients with guttate psoriasis. Future studies should examine the potential for guselkumab to induce drug-free remissions in guttate psoriasis.

Development of SkinTracker, an integrated dermatology mobile app and web portal enabling remote clinical research studies.

Introduction: In-person dermatology clinical research studies often face recruitment and participation challenges due to travel-, time-, and cost-associated barriers. Studies incorporating virtual/asynchronous formats can potentially enhance research subject participation and satisfaction, but few mobile health tools are available to enable remote study conduct. We developed SkinTracker, a patient-facing mobile app and researcher-facing web platform, that enables longitudinal collection of skin photos, patient reported outcomes, and biometric health and environmental data. Methods: Eight design thinking sessions including dermatologists, clinical research staff, software engineers, and graphic designers were held to create the components of SkinTracker. Following iterative prototyping, SkinTracker was piloted across six adult and four pediatric subjects with atopic dermatitis (AD) of varying severity levels to test and provide feedback on SkinTracker for six months. Results: The SkinTracker app enables collection of informed consent for study participation, baseline medical history, standardized skin photographs, patient-reported outcomes (e.g., Patient Oriented Eczema Measure (POEM), Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI)), medication use, adverse events, voice diary to document qualitative experiences, chat function for communication with research team, environmental and biometric data such as exercise and sleep metrics through integration with an Apple Watch. The researcher web portal allows for management and visualization of subject enrollment, skin photographs for examination and severity scoring, survey completion, and other patient modules. The pilot study requested that subjects complete surveys and photographs on a weekly to monthly basis via the SkinTracker app. Afterwards, participants rated their experience in a 7-item user experience survey covering app function, design, and desire for participation in future studies using SkinTracker. Almost all subjects agreed or strongly agreed that SkinTracker enabled more convenient participation in skin research studies compared to an in-person format. Discussion: To our knowledge, SkinTracker is one of the first integrated app- and web-based platforms allowing collection and management of data commonly obtained in clinical research studies. SkinTracker enables detailed, frequent capture of data that may better reflect the fluctuating course of conditions such as AD, and can be modularly customized for different skin conditions to improve dermatologic research participation and patient access.

Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: A 2015-2022 prospective cohort analysis of the CorEvitas psoriasis registry.

BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.