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Background: The Hand Eczema Severity Index (HECSI) is a Clinician-Reported Outcome measure of the severity of hand eczema (HE)., Objectives: This study aimed to evaluate the validity, reliability and ability to detect change of the HECSI, and the HECSI-75 and HECSI-90 as responder definitions., Methods: Analyses were performed using data from a sample of n = 258 patients with Chronic Hand Eczema (CHE) from a Phase 2b, randomised, double-blind, vehicle-controlled trial of delgocitinib cream, pooled across treatment groups. The measurement properties of the HECSI were assessed and the adequacy of the HECSI-75 and HECSI-90 as responder definitions was explored through cross-tabulation., Results: Inter-item correlations provided support for the scoring, whereby items are grouped by areas of the hand. HECSI demonstrated good test-retest reliability with intra-class correlations >0.70. Construct validity was supported by a logical pattern of correlations with concurrent measures and significant differences in HECSI scores across severity groups (p < 0.001). HECSI was responsive with statistically significant improvements over time and with significant differences (p < 0.001) between improved and stable groups. Data provided support for both HECSI-75 and HECSI-90 as within-patient responder definitions., Conclusions: HECSI has strong validity, reliability and ability to detect change as a measure of CHE severity. HECSI-75 and HECSI-90 are appropriate responder definitions., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Introduction: Chronic Hand Eczema (CHE) is an inflammatory skin disease that causes significant impact on health-related quality of life (HRQoL). The Hand Eczema Impact Scale (HEIS) is a new patient-reported outcome (PRO) measure designed to assess the impact of CHE on key domains of HRQoL. This study aimed to develop and evaluate content and psychometric validity of the HEIS., Methods: The HEIS was initially developed on the basis of a literature review and concept elicitation interviews. Qualitative cognitive debriefing interviews (n = 20) were conducted with patients with CHE to assess relevance and understanding of items, response options, and recall period. Psychometric properties (item performance, dimensionality, reliability, validity, responsiveness, and estimation of meaningful change thresholds) were then assessed using data (n = 258) from a phase 2b trial (NCT03683719)., Results: Cognitive debriefing confirmed all items were understood and relevant to patients. Inter-item correlations (all > 0.50) and confirmatory factor analysis (factor loadings ≥ 0.80) supported unidimensionality of the HEIS score, and mostly provided support for the HEIS Proximal Daily Activity Limitations (PDAL) score, with only one item loading below the prespecified threshold. Item properties and previous qualitative work supported retaining this item in the total score but removed from the HEIS PDAL domain. Internal consistency (Cronbach's alpha ≥ 0.89) and test-retest reliability (intra-class correlation coefficient ≥ 0.79) results were very strong. Strong correlations with concurrent measures (0.66-0.87) and significant differences between severity groups (p < 0.001) supported construct validity. Large effect sizes for mean change scores in participants that improved and significant differences between groups indicated ability to detect change. Anchor-based analyses supported within-individual responder definitions of ≥ 1.3 points for improvements in both HEIS score and HEIS PDAL score (covering three items) and of ≥ 1.5 points for HEIS embarrassment with the appearance of hands (Emb) score (covering two items)., Conclusions: The 9-item HEIS is the first CHE-specific PRO measure developed and validated according to regulatory guidance for assessment of the impact of CHE on key domains of HRQoL. This article provides evidence of strong content and psychometric validity and shows improvements of ≥ 1.3 points in HEIS score and HEIS PDAL score, and improvements of ≥ 1.5 points in HEIS Emb score represent clinically meaningful, important changes., Trial Registration: NCT03683719., Competing Interests: Declarations Conflict of Interest Elke Weisshaar was/is a consultant and/or investigator and/or received research money from Galderma, German Research Foundation (DFG), German Statutory Insurance (DGUV), Kiniksa, LEO Pharma, Sanofi, Trevi. Yasemin Topal Yüksel has given lectures or participated in clinical studies for Pfizer, Karo Pharma, Pierre Fabre, LEO Pharma, and AbbVie. Tove Agner has given lectures, participated in clinical studies, or been on advisory boards for Sanofi, LEO Pharma, Pfizer, Eli Lilly, Galderma, AbbVie, and Almirall. Lotte Seiding Larsen was an employee of LEO Pharma A/S at the time the work was conducted and now is an employee of H. Lundbeck A/S, Valby, Denmark. Laura Grant, Rob Arbuckle and Amy Jones are employees of Adelphi Values, a health outcomes agency contracted by LEO Pharma A/S to conduct the research. Piper Fromy (formally Philip Griffiths) was an employee of Adelphi Values at the time the work was conducted and is now an employee of Seeing Theta. Cherry Lou Balita-Crisostomo, Nanna Nyholm Mathiasen and Henrik Thoning, employees of LEO Pharma A/S, Ballerup, Denmark. Christian Apfelbacher has received institutional funding from Dr. August Wolff Group and Bionorica SE, and honorariums for consultancy work and talks from Dr. August Wolff Group, Bionorica SE, LEO Pharma, RHEACELL, Sanofi Genzyme, Pfizer, Incyte and Effik SA. Ethical Approval All participants provided informed consent indicating their data will be used for medical research purposes and the study results may be published. The studies were performed in accordance with the Helsinki Declaration of 1964 and its later amendments. Ethical approval and oversight for the qualitative interviews was obtained from Western Copernicus Group Independent Review Board (WCGIRB; reference ADE1-17–162). Ethical approval for the psychometric validation activities was obtained as part of the phase 2b trial (NCT03683719) from the independent institutional review board (IRB) and ethics committees listed in Table S1., (© 2024. The Author(s).)

Background: Chronic Hand Eczema (CHE) is a heterogeneous fluctuating inflammatory disease that represents a significant burden. Effective treatment options for moderate to severe CHE are limited., Objectives: To assess how patients with moderate to severe CHE are treated in clinical practice., Methods: A retrospective, physician-led patient record review assessed the demographic, clinical and treatment characteristics of patients aged ≥18 years with CHE across seven countries. Each participating physician was requested to review records for their three most recent patients with moderate to severe CHE treated with a topical or systemic therapy., Results: A total of 264 physicians, of whom 88.6% were dermatologists and 70.1% were predominantly or partly hospital-based, reviewed the records of 792 patients. Signs were present on hands only in 56.4% of patients and the mean time on current treatment was 16.7 months. Overall, 62.9% of patients received systemic therapy and almost one-quarter (23.4%) were treated with a biologic; 28.6% of patients were only treated with topical corticosteroids and/or topical calcineurin inhibitors., Conclusion: In patients with moderate to severe CHE, most received systemic therapy with one-quarter on biologic therapy. However, given that many of these treatments have limited evidence of efficacy in CHE, there is a need for studies specifically in patients with CHE as well as new therapeutic options., (© 2024 LEO Pharma. Contact Dermatitis published by John Wiley & Sons Ltd.)

The Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) is a novel Clinician-Reported Outcome measure that allows investigators to assess cross-sectional CHE global disease severity using clinical characteristics of erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, and fissures as guidelines for overall severity assessment. This study aimed to evaluate the psychometric properties of the IGA-CHE for use as an outcome measure in CHE clinical trials and clinical practice. Psychometric analyses were performed using data from a sample of 280 patients with moderate to severe CHE from a phase 3 trial of delgocitinib cream, pooled across treatment groups. Test-retest reliability results were moderate to strong with kappa coefficients ranging from 0.63 to 0.76. Correlations with measures assessing related concepts were moderate or strong (range 0.65-0.72) and exceeded a priori hypotheses, providing evidence of convergent validity. Known-groups validity was supported by statistically significant differences between severity groups (< 0.001). Within-group effect sizes were consistently larger for improved groups compared to stable groups, providing evidence of ability to detect change. Anchor-based analyses generated within-subject meaningful change estimates ranging from - 0.8 to - 2.3. A correlation weighted average suggested a single value of - 1.7 in change from baseline. These findings provide evidence the IGA-CHE scale has strong reliability, construct validity, and ability to detect change, supporting its use as an endpoint in CHE clinical trials and clinical practice. Based on the evidence, 2-level changes in IGA-CHE score are considered a conservative meaningful change threshold; however, findings also indicate 1-level change in IGA-CHE scores reflects a clinically meaningful improvement for patients.Clinical trial registration: NCT04871711., (© 2024. The Author(s).)

Background and Objectives: Once-daily, fixed-combination calcipotriol 50 μg/g (Cal) plus betamethasone dipropionate 0.5 mg/g (BD) is available in aerosol foam and cream formulations. As no head-to-head data are available, we use a matching-adjusted indirect comparison (MAIC) approach to compare Cal/BD foam and cream., Methods: Anchored and unanchored MAIC analyses were conducted using individual patient data (IPD) from five Cal/BD foam trials and two trials of Cal/BD cream. Outcomes of interest were the proportion of patients with Physician's Global Assessment (PGA) success and the mean reduction in modified Psoriasis Area and Severity Index (mPASI)., Results: In the anchored MAIC, patients were more likely to achieve PGA success after 4 weeks of Cal/BD foam than after 8 weeks of Cal/BD cream and had larger mean improvements in mPASI ( p  < .01 in EU mPASI analysis). In unanchored analyses, 4 weeks of Cal/BD foam treatment was statistically significantly more efficacious in inducing PGA success than 8 weeks of Cal/BD cream ( p  < .01 in five of six comparisons). Mean reductions in mPASI were consistently statistically significantly greater with Cal/BD foam than with Cal/BD cream., Conclusions: Use of Cal/BD foam consistently shows significantly greater improvements in PGA and mPASI outcomes, compared with Cal/BD cream.

Introduction: To date, there have been no head-to-head clinical studies comparing calcipotriol 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) aerosol foam and halobetasol propionate 0.01% plus tazarotene 0.045% (HP/Taz) lotion for the treatment of plaque psoriasis. However, the efficacy of 4 weeks of Cal/BD foam and 8 weeks of HP/Taz lotion has been compared using a matching-adjusted indirect comparison (MAIC) approach. Here, we compare the efficacy and safety of Cal/BD foam and HP/Taz lotion for up to 52 weeks., Methods: An unanchored MAIC was conducted using individual patient data from the PSO-LONG Cal/BD foam trial and a 52-week, open-label phase 3 study of HP/Taz lotion (NCT02462083). Key outcomes of interest were Physician's Global Assessment (PGA) success (PGA 0/1 with ≥ 2-point improvement) after 4 or 8 weeks of open-label therapy; the proportion of patients who had body surface area affected (BSA) ≤ 3 after open-label therapy who maintained BSA ≤ 3 to week 52; and adverse events (AEs)., Results: After matching, patients were statistically significantly more likely to have PGA success after 4 weeks of Cal/BD foam than after 8 weeks of HP/Taz lotion (84.5% versus 54.4%; p < 0.01). At week 52, 92.5% and 92.4% of patients receiving proactive and reactive Cal/BD foam, respectively, maintained BSA ≤ 3, compared with 49.3% of those treated with HP/Taz lotion (both p < 0.01). Treatment-related AEs, AEs leading to withdrawal, and AEs associated with drug application (dermatitis, application site pain, and pruritus) were significantly rarer with Cal/BD foam than with HP/Taz lotion (all p < 0.01)., Conclusions: Cal/BD aerosol foam demonstrated significantly greater efficacy than HP/Taz lotion, and had a more favorable safety profile, compared with HP/Taz lotion, for up to 52 weeks. Proactive Cal/BD foam maintenance therapy and reactive use of Cal/BD foam following relapse both had significant advantages over HP/Taz lotion., (© 2022. The Author(s).)

Background: Psoriasis contributes to unemployment, work impairment, missed workdays and substantial indirect costs due to lost productivity. Combination Cal/BD foam is the only topical that is approved for long-term maintenance treatment of plaque psoriasis for 52 weeks. This is the first known investigation of the effect of topical psoriasis therapy on productivity., Objective: To examine the change in work productivity and activity impairment after 4 weeks of treatment with fixed-dose combination calcipotriol 50 µg/g/betamethasone dipropionate 0.5 mg/g (Cal/BD) foam and observe long-term changes after 52 weeks of long-term management (proactive or reactive treatment)., Methods: This is a post-hoc analysis of the PSO-LONG trial - a phase 3, randomized, double-blind, vehicle-controlled, parallel group, international multi-centre trial of treatment with combination Cal/BD foam. Work and activity impairment due to psoriasis were assessed by the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment Psoriasis (WPAI:PSO) questionnaire at baseline, week 4, week 28 and week 56. The improvement in hours of work productivity was translated into monthly and annual indirect cost savings estimates for patients in Italy, Sweden, United Kingdom, Canada and Germany., Results: Using fixed-dose combination Cal/BD foam for four weeks significantly reduced psoriasis-related work presenteeism, total work productivity impairment (TWPI) and total activity impairment (TAI) over 56 weeks, with significant improvements observed as early as 4 weeks after the baseline visit. The proportion of patients reporting impact on work productivity (as measured by presenteeism and TWPI) and activity impairment (as measured by both DLQI-Q7b and TAI) also decreased., Conclusion: Fixed-dose combination Cal/BD foam used for long-term management of psoriasis significantly reduces psoriasis-related work productivity and activity impairment which may result in substantial indirect cost savings. Clinical Trial Registration NCT02899962, EudraCT number: 2016-000556-95., (© 2022 European Academy of Dermatology and Venereology.)

Background: Proactive management of plaque psoriasis with twice-weekly topical calcipotriol/betamethasone dipropionate (Cal/BD) foam has a demonstrated clinical benefit in preventing disease relapse compared to reactive management, where Cal/BD foam is only given as rescue therapy once-daily for four weeks after relapse. The impact of proactive management with Cal/BD foam on a wider range of clinical responses is not yet known, nor is its potential cost-effectiveness in the healthcare system of Finland., Methods: This study involved a post-hoc analysis exploring the clinical and patient-reported benefits of proactive versus reactive management with Cal/BD foam observed in the PSO-LONG trial (NCT02899962). A range of response criteria based on modified psoriasis area and severity index (mPASI) and dermatology life quality index (DLQI) were analyzed, and the cost-effectiveness of proactive versus reactive management was estimated in a Finnish healthcare setting., Results and Conclusion: The analysis found a consistent clinical benefit of proactive management compared to reactive management on all response criteria, and a markedly lower cost-per-responder for the response criteria of mPASI 75, mPASI ≤ 2 and DLQ1 ≤ 1. The analysis was robust to sensitivity analyses on key inputs and demonstrates the cost and clinical benefits of proactive over reactive management of plaque psoriasis with Cal/BD foam in the Finnish healthcare setting.

Background: Psoriasis has important physical and psychosocial effects that extend beyond the skin. Understanding the impact of treatment on health-related quality of life (HRQoL) and patient-perceived symptom severity in psoriasis is key to clinical decision-making., Objectives: This post hoc analysis of the PSO-LONG trial data assessed the impact of long-term proactive or reactive management with fixed-dose combination calcipotriene 50 µg/g and betamethasone dipropionate 0.5 mg/g (Cal/BD) foam on patient-reported outcomes (PROs) in patients with psoriasis vulgaris., Methods: Five hundred and twenty-one patients from the Phase 3, randomized, double-blind PSO-LONG trial were included. An initial 4-week, open-label phase of fixed-dose combination Cal/BD foam once daily (QD) was followed by a 52-week maintenance phase, at the start of which patients were randomized to a proactive management arm (Cal/BD foam twice weekly) or reactive management arm (vehicle foam twice weekly). Patient-perceived symptom severity and HRQoL were assessed using the Psoriasis Symptom Inventory (PSI), the Dermatology Life Quality Index (DLQI) and the EuroQol-5D for psoriasis (EQ-5D-5L-PSO)., Results: Statistically and clinically significant improvements were observed across all PRO measures. The mean difference (standard deviation) from baseline to Week 4 was -8.97 (6.18) for PSI, -6.02 (5.46) for DLQI and 0.11 (0.15) for EQ-5D-5L-PSO scores. During maintenance, patients receiving reactive management had significantly higher DLQI (15% [p = 0.007]) and PSI (15% [p = 0.0128]) and a numerically lower EQ-5D-5L-PSO mean area under the curve score than patients receiving proactive management (1% [p = 0.0842])., Conclusions: Cal/BD foam significantly improved DLQI, EQ-5D-5L-PSO and PSI scores during the open-label and maintenance phases. Patients assigned to proactive management had significantly better DLQI and PSI scores and numerically better EQ-5D-5L-PSO versus reactive management. Additionally, baseline flare was associated with worse PROs than the start of a relapse, and patients starting a relapse also had worse PROs than patients in remission., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Reduction of psoriasis body surface area (BSA) is associated with improved patient quality of life. Post-hoc analyses of the PSO-LONG study compared impact on BSA of proactive management versus reactive management strategies using calcipotriol/betamethasone dipropionate (Cal/BD) foam. Mean BSA values, as well as normalized area under the curves (AUCs) for patient BSA were assessed. Analyses found that after the PSO-LONG study&rsquo;s four-week open-label lead-in phase, when all patients received once-daily Cal/BD foam, mean BSA was significantly reduced. Thereafter, mean BSA remained at lower levels in patients on proactive management compared to reactive management. This was reflected in AUC BSA, which was consistently lower in the proactive management arm. Treatment-related differences were statistically significant when analyzing the full analysis set (FAS) population, as well as when restricting the analysis to study completers. Additional analyses restricted the dataset to include only observations from psoriasis remission periods, or periods of disease relapse. Treatment-related differences in AUC were statistically significant in observations during remission, but not during relapse. This could be expected given the trial&rsquo;s design, wherein all patients who relapsed were offered the same rescue therapy with once daily Cal/BD foam. Similarly, for patients who dropped out, there was no treatment-related difference in mean BSA during the two weeks preceding dropout, likely due to the common occurrence of relapse in these patients. This paper found that proactive management, in addition to preventing more relapses as previously shown, also maintained BSA at a lower level during remission than reactive management. J Drugs Dermatol. 20(5):567-570. doi:10.36849/JDD.5870.

Background: The types and quantity of non-response in surveys influence the extent to which the results may be generalized. This study analysed trends in non-response in the Danish Health Interview Surveys from 1987 to 1994 and used the National Patient Registry to assess whether non-response biased the estimated population prevalence of morbidity when solely based on responders., Methods: The data were for the 23,096 adults sampled for the Danish Health Interview Surveys in 1987, 1991 and 1994. All were followed using the National Patient Registry to obtain such information as hospital admissions., Results: Non-response increased from 20.0% in 1987 to 22.6% in 1994. Four combinations of background variables characterized the non-response: gender and age; gender and civil status; county of residence and age; survey year and age. Non-respondents and respondents had identical gender- and age-standardized hospital admission rates for approximately 5 years before and 2 years after data collection, but non-respondents had a significantly higher rate immediately before and during data collection. Admissions rates were analysed according to reasons for non-response. Refusers had a lower admission rate than respondents before data collection but similar during and after data collection. The rate was higher during the whole period among ill or disabled non-respondents. Among people who could not be contacted during the data collection period a higher admission rate was only found immediately before and during data collection., Conclusions: Although admission rates differed between respondents and non-respondents these differences were too small to bias the estimated population prevalence of morbidity when solely based on respondents.

It is well established that self-rated health (SRH) predicts mortality even after controlling for a wide range of factors. We explored the extent to which age and social relations (structural and functional) influenced the relationship between SRH and mortality (after 13 years follow-up) in a representative sample of adult Danes (N=6693). After controlling for socioeconomic status, illness, and lifestyle variables, we found that age moderated the SRH-mortality relationship such that it was present for respondents under 55 but absent for respondents over 56. In addition, weaker structural (but not functional) social relations increased mortality directly but neither structural nor functional social relations moderated the SRH-mortality relationship. We discuss the theoretical and practical implications of these findings.

Observational studies and recent randomized trials have shown that postmenopausal hormone replacement therapy (HRT) may reduce the risk of osteoporotic fractures by about 30 to 40%. In this study we used a log linear graphical model to determine whether women with a known increased risk of osteoporosis were more likely to use HRT than other women and to examine whether women at increased risk modified this risk through their lifestyle. Cox regression analysis was used to analyze if women at risk of osteoporosis used HRT longer than women not at risk. Participants were Danish female nurses who, in 1993, were between 50 and 69 years of age (N=14,865). Data were collected from postal questionnaires. We concluded that nurses with a known family history of osteoporosis more often used HRT than nurses without this risk. No other direct associations were found between biological risk factors and ever use of HRT. The presence of biological risk factors of osteoporosis was not consistently modified by a healthier lifestyle. Nurses with a low body mass index (BMI) with a known family history of osteoporosis continued to use HRT longer than nurses without these risk factors.

Background: Studies have found that women who use hormone replacement therapy (HRT) are healthier or report better health than non-users. This study examines the association between lifestyle factors, self-reported health and the use of HRT in Danish female nurses above the age of 50 years., Methods: Postal questionnaires were used for data collection. Two cohorts were examined, a younger including women between 50 and 59 years and an older including women of 60 years and above., Results: Of the 14,071 nurses included, 5,528 (39%) reported ever using HRT. In both cohorts, ever using HRT was positively associated (odds ratio > 1) with intake of vitamin supplements, alcohol consumption at weekends, consulting a physician, use of medicine, and previous use of oral contraceptives. Only a few differences were found between former and current users of HRT. A highly significant association was found between ever using HRT and self-reported poor health., Conclusions: In this study use of HRT was not found to be associated with a particularly healthy lifestyle or better health. Therefore, these factors should be specifically considered in studies evaluating the effect of HRT.

Aim: To estimate risk of infectious endophthalmitis after cataract extraction in Denmark and to compare results with the risk of this complication in the USA., Methods: In the national Danish administrative hospital register, 19,426 patients were identified who underwent first eye cataract surgery from 1985 to 1987 and who were 50 years of age or older. Of these, 61 patients had postoperative endophthalmitis., Results: A 12 month cumulative risk of rehospitalisation for endophthalmitis was estimated at 0.18% (95% CI 0.09-0.26) after extracapsular cataract extraction with lens implant. Advanced age, male sex, intracapsular cataract extraction, and anterior vitrectomy were all associated independently with an increased risk of postoperative endophthalmitis. When restricting the sample to patients aged 65 years or older, in order to allow comparisons to be made with the US National Study of Cataract Outcomes, a 12 month risk of 0.17% (95% CI 0.08-0.25) was estimated. The previously reported US risk of 0.12% is included in the confidence interval of the risk estimated in the Danish sample., Conclusion: Despite considerable differences in the healthcare systems, no statistically significant difference in outcome of surgery as measured by risk of endophthalmitis was shown between Denmark and the USA.

Aims: To estimate the risk of retinal detachment (RD) following cataract extraction in Denmark, and to compare the risk with that following cataract extraction in the USA, and with that in a sample of Danish patients who did not have ocular surgery., Methods: A sample was created from the administrative Danish Hospital Register and included 19,252 patients who underwent first eye cataract surgery between 1985 and 1987, and who were 50 years of age or older. The patients were then followed for 4-6 years using the register data. The design and definition of events were identical to the US National Study of Cataract Outcomes., Results: In Denmark a 4 year cumulative risk of hospitalisation for RD of 0.93% (95% confidence interval (CI) 0.71-1.16) was observed following an extracapsular cataract extraction with a lens implant. A similar cumulative risk of RD was reported from the US study. Thus, no difference in outcomes concerning risk of RD was shown between Denmark and the USA. In a multivariate analysis younger age, male sex, and intracapsular cataract extraction were all associated with higher risk of postoperative RD. A reference group of 7636 people not undergoing any ocular surgery was created and the incidence of RD in this group was calculated. During the sixth year following cataract surgery, the incidence of RD in the cataract group was still 7.5 (95% CI 1.6-22.0) times higher than that observed in the reference group.