Predicting Psoriatic Arthritis in Psoriasis Patients - A Swiss Registry Study.

Background: Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis. Objectives: To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors. Methods: Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression. Results: A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model's AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA (P = .01). Conclusions: Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA.

Predictors of initiating biologics in the treatment of psoriasis.

BACKGROUND: Biologics are among the most effective therapies for psoriasis. However, many patients are only introduced to them at advanced stages of the disease course. OBJECTIVES: Our aim was to identify predictors of initiating biologic therapy in patients with psoriasis and compare patients initiating biologics early versus late in their disease course. METHODS: Kaplan-Meier curves visualized time to biologic initiation, while Cox regression models further explored variables as predictors of biologic initiation. Mann-Whitney U and chi-squared tests compared patients who started biologics early with those who began biologics later in the disease course. RESULTS: Our primary analysis included 233 psoriasis patients. Cox regression showed that age at diagnosis (P = 0.007), general physical well-being (P = 0.02), and nail psoriasis severity (P = 0.02) were significantly associated with time to biologic initiation. Our secondary analysis, the comparisons between patients starting biologics early versus later in the disease course, included a total of 378 patients. The median (interquartile range [IQR]) age at diagnosis was 34.5 (25.0-51.2) years for patients initiating biologics within 5 years, compared to 22.0 (15.0-32.8) years for patients initiating biologics later (P < 0.0001). The median (IQR) age at initiation was 37.0 (27.0-53.2) and 45.0 (36.0-55.0) years for patients initiating biologics earlier versus later than 5 years (P = 0.04). CONCLUSIONS: Age at diagnosis, general well-being, and severity of nail psoriasis significantly predicted future initiation of biologic treatment. Patients initiating biologics early in their disease course were generally older at diagnosis but younger at the time of biologic initiation compared to patients initiating biologics later in their disease course.

Impact of the pre-biologic treatment journey on biologic drug survival in psoriasis: A nationwide cohort study.

BACKGROUND: It is unknown whether the pre-biologic treatment journey affects subsequent biologic drug survival. OBJECTIVE: To examine the potential impact of a complex treatment journey on subsequent biologic drug survival in patients with psoriasis. METHODS: The study utilized longitudinal data from Danish national registries and included all patients who, for the first time, initiated a biological treatment for psoriasis. Maximum follow-up was 5 years and patients were included from 1 January 2010 to 30 June 2021. The study used three definitions of exposure to a complex treatment journey and the following conventional systemic treatments: acitretin, cyclosporine, dimethyl fumarate and methotrexate. The first definition was the cumulative number of treatment series. The second definition comprised the number of unique treatments. The third definition was time from the first conventional systemic treatment to biological therapy. Drug survival for the three definitions were illustrated using Kaplan-Meier curves and compared using log-rank test. The sensitivity analysis largely confirmed these findings by grouping patients according to pharmacotherapy. RESULTS: A total of 2496 patients were included in the study, with 1380 (55.3%) receiving adalimumab, 608 (24.4%) receiving ustekinumab, 271 (10.9%) receiving secukinumab, 166 (6.7%) receiving etanercept and 71 (2.8%) receiving infliximab. The mean age at initiation of biologics was 43.6 years (standard deviation (SD) 15.2 years), and most patients were male (62.9%). During the follow-up of 5477 patient years, 1953 patients (78.2%) reached the main endpoint of discontinuation. Using a log-rank test, the probability of remaining on treatment was unaffected by the three definitions of complexity of the treatment journey. CONCLUSION: None of the three exposures used to assess the complexity of the pre-biologic treatment journey appeared to impact drug survival. As long as patients experience adequate disease control, these results suggest that conventional systemic treatment do not negatively impact the drug survival of subsequent biologics.

Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study.

BACKGROUND: Flare patterns are not routinely considered in the severity classification or in clinical decision-making of atopic dermatitis (AD), but frequent or severe flares may contribute considerably to the disease burden. OBJECTIVES: To characterize patients with AD in relation to their flare pattern and compare flare patterns to disease severity, life quality and treatment satisfaction. METHODS: Patients with AD from the Danish Skin Cohort were included if they had active AD with and available data on number of flare-ups within the last 12 months. Categorical variables were presented as frequencies and percentages, whereas numerical variables were presented as median and interquartile ranges (IQR). Between-group differences were tested with chi-squared tests. RESULTS: A total of 1557 patients were included, with 57 reporting 0 flares, 698 (1-5 flares), 324 (6-10 flares) and 478 reporting >10 flares during the past 12 months. Both the severity measured by PO-SCORAD and the impairment of life quality measured by DLQI were higher among patients with more flares (median [IQR] PO-SCORAD: 13.0 [5.6-22.3], 29.7 [20.8-40.6], 36.3 [26.7-47.6]and 42.9 [30.7-55.6], respectively for the four flares strata, and median [IQR] DLQI: 1.0 [0.0-2.0], 3.0 [1.0-7.0], 4.0 [1.8-9.0] and 7.0 [3.0-11.0]). Satisfaction with the current treatment was generally higher among patients with no flares. However, 36.8%, 24.6% and 23.7% of patients with 1-5, 6-10 and >10 flares reported being extremely or very satisfied with their current treatment. CONCLUSIONS: Patients with many flares often report a higher severity and impairment of life quality compared to patients with fewer flares. Information on flaring could benefit treatment decisions, thereby decreasing undertreatment of patients with mild AD but severe flaring.

Correlation between Dermatology Life Quality Index and Psoriasis Area and Severity Index in Patients with Psoriasis: A Cross-sectional Global Healthcare Study on Psoriasis.

Quality of life impairment in dermatology patients and severity of psoriasis are quantified by the Dermatology Life Quality Index (DLQI) and the Psoriasis Area and Severity Index (PASI), respectively. The aim of this study is to compare the correlation between PASI and DLQI in patients from different geographical areas and to identify predictors of high DLQI across geographical regions. Correlations between PASI and DLQI were evaluated using Spearman's rank correlation tests and quantile regression. The study included 1,158 patients with psoriasis, with a median (interquartile range) PASI and DLQI of 6.0 (3.0-12.0) and 8.0 (4.0-15.0), respectively. Correlations were demonstrated between PASI and DLQI, both overall and stratified by geographical region. Quantile (median) regression yielded coefficients of 0.75 (95% confidence interval (95% CI) 0.62, 0.88) for Switzerland, 0.50 (95% CI 0.42, 0.58) for Latin America, 0.34 (95% CI 0.16, 0.51) for Asia, and 0.31 (95% CI 0.08, 0.53) for the USA. Current age, age at diagnosis, sex, body mass index, and psoriasis arthritis affected DLQI in Latin America, while education had an impact among patients treated in Switzerland. Few countries were included within each continent; hence, more data from different countries are necessary for generalizability. The study showed correlations between PASI and DLQI among patients in all included geographical regions. The patients' characteristics affecting DLQI vary worldwide.

Use of compression therapy for cellulitis.

INTRODUCTION: Cellulitis is a common infection, especially among the elderly, and compression therapy is often recommended to reduce acute oedema and pain. A previous study showed that compression therapy led to a lower incidence of recurrent cellulitis in lower extremities in patients with chronic oedema. The aim of this study was to describe clinical characteristics of patients with cellulitis. METHODS: This was a retrospective descriptive study reviewing medical records and medicine registrations in patients ≥ 18 years with cellulitis. RESULTS: A total of 104 patients were hospitalised with cellulitis; 13 were excluded. The median age was 75 years (range: 33-103 years), 64% > 70 years. The median admission time was five days (range: 1-24 days). Median antibiotic treatment duration was 11 days (range: 4-56 days). A total of 45% were current or former smokers, 40% were overweight, 48% had preexisting chronic oedema of the affected area, 90% had become infected in the lower extremities and 19% were readmitted within six months. A total of 51% had a new antibiotic treatment prescribed after being discharged, and 66% received compression therapy. CONCLUSIONS: Cellulitis frequently affects older patients, especially smokers, people with overweight and chronic lymphoedema. In all, 66% were treated with compression therapy that did not have a clear effect on their readmission rate, probably because the patients receiving compression therapy had a more severe infection complicated by severe oedema and a higher risk of reinfection. An increased focus on the use of compression therapy in conjunction with health preventive interventions may have a positive impact on the relapse rate. FUNDING: None. TRIAL REGISTRATION: Not relevant.

The evolution of menopause in toothed whales.

Understanding how and why menopause has evolved is a long-standing challenge across disciplines. Females can typically maximize their reproductive success by reproducing for the whole of their adult life. In humans, however, women cease reproduction several decades before the end of their natural lifespan1,2. Although progress has been made in understanding the adaptive value of menopause in humans3,4, the generality of these findings remains unclear. Toothed whales are the only mammal taxon in which menopause has evolved several times5, providing a unique opportunity to test the theories of how and why menopause evolves in a comparative context. Here, we assemble and analyse a comparative database to test competing evolutionary hypotheses. We find that menopause evolved in toothed whales by females extending their lifespan without increasing their reproductive lifespan, as predicted by the 'live-long' hypotheses. We further show that menopause results in females increasing their opportunity for intergenerational help by increasing their lifespan overlap with their grandoffspring and offspring without increasing their reproductive overlap with their daughters. Our results provide an informative comparison for the evolution of human life history and demonstrate that the same pathway that led to menopause in humans can also explain the evolution of menopause in toothed whales.

Effects of oral roflumilast therapy on body weight and cardiometabolic parameters in patients with psoriasis - results from a randomized controlled trial (PSORRO).

BACKGROUND: Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. OBJECTIVE: To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. METHODS: Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 µg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. RESULTS: Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was -2.6% and -4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. LIMITATIONS: Posthoc analyses and low numbers. CONCLUSION: Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis.

Atopic dermatitis phenotypes based on cluster analysis of the Danish Skin Cohort.

BACKGROUND: Despite previous attempts to classify atopic dermatitis (AD) into subtypes (e.g. extrinsic vs. intrinsic), there is a need to better understand specific phenotypes in adulthood. OBJECTIVES: To identify, using machine learning (ML), adult AD phenotypes. METHODS: We used unsupervised cluster analysis to identify AD phenotypes by analysing different responses to predetermined variables (age of disease onset, severity, itch and skin pain intensity, flare frequency, anatomical location, presence and/or severity of current comorbidities) in adults with AD from the Danish Skin Cohort. RESULTS: The unsupervised cluster analysis resulted in five clusters where AD severity most clearly differed. We classified them as 'mild', 'mild-to-moderate', 'moderate', 'severe' and 'very severe'. The severity of multiple predetermined patient-reported outcomes was positively associated with AD, including an increased number of flare-ups and increased flare-up duration and disease severity. However, an increased severity of rhinitis and mental health burden was also found for the mild-to-moderate phenotype. CONCLUSIONS: ML confirmed the use of disease severity for the categorization of phenotypes, and our cluster analysis provided novel detailed information about how flare patterns and duration are associated with AD disease severity.

Acceptance of Telemedicine Compared to In-Person Consultation From the Providers' and Users' Perspectives: Multicenter, Cross-Sectional Study in Dermatology.

BACKGROUND: Teledermatology is currently finding its place in modern health care worldwide as a rapidly evolving field. OBJECTIVE: The aim of this study was to investigate the acceptance of teledermatology compared to in-person consultation from the perspective of patients and professionals. METHODS: This multicenter, cross-sectional pilot study was performed at secondary and tertiary referral centers of dermatology in Switzerland from August 2019 to January 2020. A customized questionnaire addressing demographics and educational data, experience with telemedicine, and presumed willingness to replace in-patient consultations with teledermatology was completed by dermatological patients, dermatologists, and health care workers in dermatology. RESULTS: Among a total of 664 participants, the ones with previous telemedicine experience (171/664, 25.8%) indicated a high level of overall experience with it (patients: 73/106, 68.9%, dermatologists: 6/8, 75.0%, and health care workers: 27/34, 79.4%). Patients, dermatologists, and health care workers were most likely willing to replace in-person consultations with teledermatology for minor health issues (353/512, 68.9%; 37/45, 82.2%; and 89/107, 83.2%, respectively). We observed a higher preference for telemedicine among individuals who have already used telemedicine (patients: P<.001, dermatologists: P=.03, and health care workers, P=.005), as well as among patients with higher educational levels (P=.003). CONCLUSIONS: This study indicates that the preference for teledermatology has a high potential to increase over time since previous experience with telemedicine and a higher level of education were associated with a higher willingness to replace in-patient consultations with telemedicine. We assume that minor skin problems are the most promising issue in teledermatology. Our findings emphasize the need for dermatologists to be actively involved in the transition to teledermatology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04495036; https://classic.clinicaltrials.gov/ct2/show/NCT04495036.

Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis-a randomized controlled trial (PSORRO).

Background: Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied. Methods: A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 µg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12. Findings: In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events. Interpretation: Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments. Funding: Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.

Energy expenditure of southern right whales varies with body size, reproductive state and activity level.

Quantifying the energy expenditure of animals is critical to understanding the cost of anthropogenic disturbance relative to their overall energy requirements. We used novel drone focal follows (776 follows, 185 individuals) and aerial photogrammetry (5372 measurements, 791 individuals) to measure the respiration rate and body condition loss of southern right whales (Eubalaena australis) on a breeding ground in Australia. Respiration rates were converted to oxygen consumption rate and field metabolic rate (FMR) using published bioenergetic models. The intra-seasonal loss in body condition of different reproductive classes (calves, juveniles, adults, pregnant and lactating females) was converted to blubber energy loss and total energy expenditure (TEE). Using these two metrics, we tested the effects of body size, reproductive state and activity level on right whale energy expenditure. Respiration rates and mass-specific FMR decreased exponentially with an increase in body size, as expected based on allometric scaling. FMR increased curvilinearly with an increase in swim speed, probably as a result of increased drag and increased locomotion costs. Respiration rates and FMR were 44% higher for pregnant and lactating females compared with those of adults, suggesting significant costs of fetal maintenance and milk production, respectively. The estimated FMR of adults based on their respiration rates corresponded well with the estimated TEE based on body condition loss. The rate of decline in body condition of pregnant and lactating females was considerably higher than expected based on respiration rates, which probably reflects the milk energy transfer from mothers to calves, which is not reflected in their FMR.

Temporal dynamics of mother-offspring relationships in Bigg's killer whales: opportunities for kin-directed help by post-reproductive females.

Age-related changes in the patterns of local relatedness (kinship dynamics) can be a significant selective force shaping the evolution of life history and social behaviour. In humans and some species of toothed whales, average female relatedness increases with age, which can select for a prolonged post-reproductive lifespan in older females due to both costs of reproductive conflict and benefits of late-life helping of kin. Killer whales (Orcinus orca) provide a valuable system for exploring social dynamics related to such costs and benefits in a mammal with an extended post-reproductive female lifespan. We use more than 40 years of demographic and association data on the mammal-eating Bigg's killer whale to quantify how mother-offspring social relationships change with offspring age and identify opportunities for late-life helping and the potential for an intergenerational reproductive conflict. Our results suggest a high degree of male philopatry and female-biased budding dispersal in Bigg's killer whales, with some variability in the dispersal rate for both sexes. These patterns of dispersal provide opportunities for late-life helping particularly between mothers and their adult sons, while partly mitigating the costs of mother-daughter reproductive conflict. Our results provide an important step towards understanding why and how menopause has evolved in Bigg's killer whales.

Costly lifetime maternal investment in killer whales.

Parents often sacrifice their own future reproductive success to boost the survival of their offspring, a phenomenon referred to as parental investment. In several social mammals, mothers continue to improve the survival of their offspring well into adulthood;1,2,3,4,5 however, whether this extended care comes at a reproductive costs to mothers, and therefore represents maternal investment, is not well understood. We tested whether lifetime maternal care is a form of parental investment in fish-eating "resident" killer whales. Adult killer whales, particularly males, are known to receive survival benefits from their mothers;3 however, whether this comes at a cost to mothers' reproductive success is not known. Using multiple decades of complete census data from the "southern resident" population, we found a strong negative correlation between females' number of surviving weaned sons and their annual probability of producing a viable calf. This negative effect did not attenuate as sons grew older, and the cost of sons could not be explained by long-term costs of lactation or group composition effects, supporting the hypothesis that caring for adult sons is reproductively costly. This is the first direct evidence of lifetime maternal investment in an iteroparous animal, revealing a previously unknown life history strategy.

Multivariable Predictive Models to Identify the Optimal Biologic Therapy for Treatment of Patients With Psoriasis at the Individual Level.

Importance: Identifying the optimal long-term biologic therapy for patients with psoriasis is often done through trial and error. Objective: To identify the optimal biologic therapy for individual patients with psoriasis using predictive statistical and machine learning models. Design, Setting, and Participants: This population-based cohort study used data from Danish nationwide registries, primarily DERMBIO, and included adult patients treated for moderate-to-severe psoriasis with biologics. Data were processed and analyzed between spring 2021 and spring 2022. Main Outcomes and Measures: Patient clusters of clinical relevance were identified and their success rates estimated for each drug. Furthermore, predictive prognostic models to identify optimal biologic treatment at the individual level based on data from nationwide registries were evaluated. Results: Assuming a success criterion of 3 years of sustained treatment, this study included 2034 patients with a total of 3452 treatment series. Most treatment series involved male patients (2147 [62.2%]) originating from Denmark (3190 [92.4%]), and 2414 (69.9%) had finished an education longer than primary school. The average ages were 24.9 years at psoriasis diagnosis and 45.5 years at initiation of biologic therapy. Gradient-boosted decision trees and logistic regression were able to predict a specific cytokine target (eg, interleukin-17 inhibition) associated with a successful treatment with accuracies of 63.6% and 59.2%, and top 2 accuracies of 95.9% and 93.9%. When predicting specific drugs resulting in success, gradient boost and logistic regression had accuracies of 48.5% and 44.4%, top 2 accuracies of 77.6% and 75.9%, and top 3 accuracies of 89.9% and 89.0%. Conclusions and Relevance: Of the treatment prediction models used in this cohort study of patients with psoriasis, gradient-boosted decision trees performed significantly better than logistic regression when predicting specific biologic therapy (by drug as well as target) leading to a treatment duration of at least 3 years without discontinuation. Predicting the optimal biologic could benefit patients and clinicians by minimizing the number of failed treatment attempts.

The road to biologics in patients with hidradenitis suppurativa: a nationwide drug utilization study.

BACKGROUND: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. OBJECTIVES: To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. METHODS: We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. RESULTS: A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]. CONCLUSIONS: Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.