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BACKGROUND: Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema. METHODS: Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101. FINDINGS: Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis. INTERPRETATION: Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids. FUNDING: LEO Pharma.
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Eccema , Dermatosis de la Mano , Pirroles , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Crónica , Método Doble Ciego , Eccema/tratamiento farmacológico , Dermatosis de la Mano/tratamiento farmacológico , Pirroles/uso terapéutico , Índice de Severidad de la Enfermedad , Crema para la Piel , Resultado del TratamientoRESUMEN
BACKGROUND: The Recap of atopic eczema questionnaire (RECAP) was developed to measure eczema control in patients with atopic dermatitis (AD). The measurement properties of RECAP have not yet been validated in caregivers of children with AD. OBJECTIVES: To assess the construct validity, responsiveness, reliability and interpretability of the Dutch proxy version of RECAP. METHODS: A prospective validation study was conducted in children (aged < 12â years) with AD and their caregivers (in a Dutch tertiary hospital). At three timepoints (T0 = baseline; T1 = after 1-7â days; T2 = after 4-8 weeks) RECAP and multiple reference instruments were completed by caregivers of child patients. Single- and change-score validity (responsiveness) were tested with a priori hypotheses on correlations with reference instruments. Intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were reported. Bands for perceived eczema control were proposed. The smallest detectable change (SDC) and minimally important change (MIC) were determined. Two anchor-based methods based on receiver operating characteristic curve (ROC) and predictive modelling were used to determine the MIC. RESULTS: A total of 231 children with AD and their caregivers participated. Of our a priori hypotheses for single-score and change-score validity, 77% and 80% were confirmed, respectively. A stronger correlation than hypothesized was found for all rejected hypotheses.Excellent reliability was found (ICCagreement = 0.94, 95% confidence interval 0.90-0.96). The SEMagreement was 1.9 points. The final banding was 0-1 (completely controlled), 2-7 (mostly controlled), 8-12 (moderately controlled), 13-18 (a little controlled) and 19-28 (not at all controlled). A cutoff point of ≥ 8 was selected to identify children whose AD is not under control. The SDC was 5.3 and the MIC values were 1.5 and 3.6 for the ROC and predictive modelling approaches, respectively. No floor or ceiling effects were observed. CONCLUSIONS: The proxy version of RECAP is a valid, reliable and responsive measurement instrument for measuring eczema control in children with AD. An improvement of ≥ 6 points can be regarded as a real and important change in children with AD.
Atopic dermatitis (AD) is a skin disease that affects children and adults. People with AD (eczema) and other stakeholders have identified perceived 'eczema control' as an important outcome to investigate in research. For this purpose, the Recap of atopic eczema (RECAP) questionnaire was developed, consisting of seven items to measure eczema control in people with AD. However, when developing questionnaires, they must be examined to ensure they are relevant, reliable and sensitive enough to detect meaningful change before and after any new treatment. Prior studies have demonstrated that the RECAP is suitable for adults with AD, but studies investigating whether the RECAP is suitable for children are lacking. A study of 231 children (under 12â years old) with AD and their caregivers was conducted in the Netherlands. Caregivers completed the RECAP questionnaire at three time points: at the start of the study, after 17â days and after 48 weeks. The researchers assessed AD severity and eczema control using other measures for comparison. RECAP scores from children whose caregivers reported unchanged eczema control were used to assess how reproducible this questionnaire was. RECAP scores of caregivers who reported change in eczema control were used to examine sensitivity to change. Statistical tests were used to analyse findings. The researchers found that RECAP accurately measures changes in eczema control over time and was sensitive enough to detect small changes in eczema control. Overall, the authors concluded that the RECAP questionnaire is valid, reproducible and responsive. Furthermore, they consider an improvement of at least 6 points to represent a genuine improvement in Dutch children.
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Cuidadores , Dermatitis Atópica , Humanos , Dermatitis Atópica/diagnóstico , Femenino , Masculino , Reproducibilidad de los Resultados , Niño , Estudios Prospectivos , Preescolar , Encuestas y Cuestionarios/normas , Encuestas y Cuestionarios/estadística & datos numéricos , Países Bajos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation; however, its role in the management of AD remains poorly understood. OBJECTIVES: To investigate the effectiveness of antibacterial therapeutic clothing + standard topical treatment in patients with moderate-to-severe AD vs. standard therapeutic clothing + standard topical treatment; and, if effectiveness was demonstrated, to demonstrate its cost-effectiveness. METHODS: A pragmatic double-blinded multicentre randomized controlled trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1 : 1 : 1 to receive standard therapeutic clothing or antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes (PROs), topical corticosteroid (TCS) use, SA colonization, safety and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed-model analyses. RESULTS: Between 16 March 2020 and 20 December 2021, 171 patients were enrolled. In total, 159 patients were included (54 in the standard therapeutic clothing group, 50 in the chitosan group and 55 in the silver group). Adherence was high [median 7 nights a week wear (interquartile range 3-7)]. Median EASI scores at baseline and at 4, 12, 26 and 52 weeks were 11.8, 4.3, 4.6, 4.2 and 3.6, respectively, in the standard therapeutic clothing group vs. 11.3, 5.0, 3.0, 3.0 and 4.4, respectively, in the chitosan group, and 11.6, 5.0, 5.4, 4.6 and 5.8, respectively, in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing group, the chitosan group [-0.1, 95% confidence interval (CI) -0.3 to 0.2; P = 0.53] or the silver group (-0.1, 95% CI -0.3 to 0.2; P = 0.58) were found. However, a small significant group × time interaction effect between the standard and silver groups was found (P = 0.03), in which the silver group performed worse after 26 weeks. No differences between groups were found in PROs, TCS use, SA skin colonization and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS: The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD.
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Quitosano , Dermatitis Atópica , Fármacos Dermatológicos , Infecciones Estafilocócicas , Humanos , Corticoesteroides/uso terapéutico , Antibacterianos/efectos adversos , Quitosano/uso terapéutico , Vestuario , Dermatitis Atópica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Método Doble Ciego , Glucocorticoides/uso terapéutico , Índice de Severidad de la Enfermedad , Plata/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited. OBJECTIVES: To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet. METHODS: In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep. RESULTS: A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P = .003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile. LIMITATIONS: Short-term, 16-week treatment period. CONCLUSION: Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition.
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Anticuerpos Monoclonales Humanizados , Dermatitis Atópica , Dermatosis del Pie , Dermatosis de la Mano , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Método Doble Ciego , Dermatitis Atópica/tratamiento farmacológico , Adulto , Adolescente , Persona de Mediana Edad , Dermatosis de la Mano/tratamiento farmacológico , Dermatosis del Pie/tratamiento farmacológico , Adulto Joven , Resultado del Tratamiento , EficienciaRESUMEN
BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.
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Anticuerpos Monoclonales Humanizados , Dermatitis Atópica , Medición de Resultados Informados por el Paciente , Sistema de Registros , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Femenino , Masculino , Adulto , Niño , Persona de Mediana Edad , Resultado del Tratamiento , Estudios Prospectivos , Adolescente , Calidad de Vida , Adulto Joven , Estudios de Seguimiento , Anciano , Conjuntivitis/inducido químicamente , Preescolar , Prurito/etiología , Prurito/tratamiento farmacológicoRESUMEN
Psoriasis, a chronic inflammatory skin disease, goes beyond visible symptoms and affects the general well-being of patients. The aim of this study is to understand how patients with psoriasis perceive their skin characteristics and reactivity to allergens. The study population includes 11,283 participants within the European Dermato-Epidemiology Network (EDEN) Fragrance study, covering several European regions. The study compared perceptions of skin dryness, sensitivity, product avoidance and reactivity to allergens between patients with psoriasis and controls, evaluating the potential influence of psoriasis severity. The results showed that subjects with psoriasis reported dry skin (71.1%) and sensitive skin (49.4%) more often than did controls (51.6% and 38.5%, respectively). Psoriasis patients were more likely to avoid specific products. Interestingly, there were no significant differences in patch-test results between the 2 groups and the severity of psoriasis did not have a consistent impact on these perceptions. In conclusion, people with psoriasis tend to perceive their skin as drier and more sensitive. Notably, the severity of psoriasis did not consistently influence these perceptions and objective reactivity to allergens did not align with subjective perception. Understanding these aspects is crucial for tailoring treatments to improve the well-being of patients with psoriasis, which warrants further research to explore subjective perceptions of skin well-being in patients with psoriasis.
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Dermatitis , Psoriasis , Humanos , Alérgenos , Odorantes , Psoriasis/diagnóstico , Psoriasis/epidemiología , Pruebas del ParcheRESUMEN
Limited daily practice data on the effect of abrocitinib in patients with atopic dermatitis are available. The aim of this multicentre prospective study is to evaluate the effectiveness and safety of abrocitinib in patients with atopic dermatitis treated in daily practice. In a subgroup, the effectiveness of abrocitinib on hand eczema was evaluated. A total of 103 patients from the BioDay registry were included in the study: week 4 (n = 95), week 16 (n = 61) and week 28 (n = 39). At week 28, the Eczema Area and Severity Index (EASI)-50/75/90 was achieved by 81.8%, 57.6%, and 18.2%, respectively, and the weekly average pruritus numerical rating scale ≤ 4 by 62.9%. The effectiveness of abrocitinib was not significantly different between dupilumab non-responders and dupilumab-naïve patients/responders, and between upadacitinib non-responders and upadacitinib-naïve patients/responders. Mean ± standard deviation Hand Eczema Severity Index decreased from 27.4 ± 27.7 at baseline to 7.7 ± 12.1 at week 28 (n = 31). Thirty-two patients (31.1%) discontinued treatment due to ineffectiveness (n = 17), adverse events (n = 9) or both (n = 3). The most frequently reported adverse event was nausea (n = 28). In conclusion, abrocitinib is an effective treatment for atopic dermatitis and can be effective for patients with previous inadequate response to dupilumab or upadacitinib. Furthermore, hand eczema can improve in patients treated with abrocitinib for atopic dermatitis.
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Dermatitis Atópica , Eccema , Pirimidinas , Sulfonamidas , Humanos , Estudios Prospectivos , Sistema de Registros , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Método Doble CiegoRESUMEN
BACKGROUND: To date, hand eczema (HE)-related presenteeism has never been assessed within the general population, and general population-based studies on HE-related sickness absence are limited. OBJECTIVES: To assess the prevalence of HE-related presenteeism and sickness absence, and factors associated with HE-related presenteeism, within the Dutch general population. METHODS: Within the Lifelines Cohort Study, participants with HE in the last year (aged 18-65 in 2020), were identified by a questionnaire including questions regarding HE-related presenteeism and sickness absence. Socio-demographic factors were collected from 2006 to 2020. RESULTS: Out of the 3.703 included participants with HE, 2.7% (n = 100) reported HE-related presenteeism, with 19.8% (n = 57) among those with severe-to-very-severe HE. HE-related sickness absence was reported by 0.5% (n = 20) and 5.9% (n = 17), respectively. Logistic regression analyses, adjusted for age and sex, showed negative associations between HE-related presenteeism and higher educational attainment, higher income (>2500) and higher occupational skill level, and positive associations for high-risk occupations, chronic HE, moderate and severe-to-very-severe HE (compared to almost clear), atopic dermatitis and occupational wet exposure. CONCLUSIONS: A high prevalence of HE-related presenteeism was found among participants with severe-to-very-severe HE. Future studies should focus on longitudinal associations with the clinical course of HE, as HE-related presenteeism might aggravate symptoms of HE.
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Dermatitis Alérgica por Contacto , Eccema , Humanos , Estudios Transversales , Presentismo , Estudios de Cohortes , Eccema/epidemiología , Encuestas y Cuestionarios , Ausencia por EnfermedadRESUMEN
BACKGROUND: Transcriptome analyses of vesicular hand eczema (VHE) indicated a large overlap with atopic dermatitis (AD). However, differentially expressed genes (DEGs) that differentiate VHE from AD are unknown. OBJECTIVE: To identify distinctive transcriptional features of VHE in comparison to AD. METHODS: We re-analysed RNA sequencing data of 10 lesional palmar VHE epidermal biopsies and performed DEG analyses. We adjusted the obtained DEG results of 57 lesional whole AD skin biopsies of the upper extremities or trunk to our criteria. Up- and down-regulated DEGs in both skin diseases, VHE-only, AD-only, and opposite regulated DEGs were identified. Enrichment analyses and Chi-squared tests were conducted to test for differences in gene set enrichment between both skin diseases. RESULTS: Comparing 3028 DEGs in VHE (1645 up; 1383 down) with 5391 DEGs in AD (3842 up; 1549 down), revealed 1516 shared DEGs (1179 up; 337 down) and 1512 DEGs unique to VHE (466 up, 1046 down). Interferon signalling and necroptosis were significantly more prominent in VHE compared to AD. Downregulated genes identified only in VHE (like DNASE1L2, KRT2, KRT9 and KRT25) indicate an aberrant epidermal differentiation. CONCLUSION: Our study indicates a common pathophysiology between VHE and AD, but also reveals transcriptional differences between VHE and AD.
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Dermatitis Alérgica por Contacto , Dermatitis Atópica , Eccema Dishidrótico , Eccema , Humanos , Dermatitis Atópica/genética , Dermatitis Alérgica por Contacto/patología , Piel/patología , Perfilación de la Expresión Génica , Eccema/genética , Desoxirribonucleasa IRESUMEN
BACKGROUND: Twin studies revealed that genetic effects play a role in hand eczema (HE), but the responsible genetic factors are unknown. OBJECTIVES: To identify and characterise genetic loci associated with HE and to provide insight into the genetic overlap between HE and atopic dermatitis (AD). METHODS: We used questionnaire-derived and genotype data from the European population-based Lifelines cohort and biobank. We performed a discovery genome-wide association study (GWAS) of HE (2879 cases and 16 249 controls) and of AD (1706 cases and 17 190 controls). We replicated our findings in an independent Lifelines sample for HE (1188 cases and 6431 controls) and AD (757 cases and 6747 controls). We conducted several post-GWAS analyses and performed genetic correlation analyses between our HE results and independent AD data. RESULTS: The two-step GWAS of HE, regardless of adjusting for AD, identified one independent locus 20q13.33, likely driven by a number of causal single-nucleotide polymorphisms. For the AD GWAS, we replicated a known stop-gained rs61816761 at locus 1q21.3 (FLG, FLGAS1). We found a strong genetic correlation (p < 0.01) between HE and AD (rg = 0.65), regardless of adjusting for AD (rg = 0.63). CONCLUSIONS: Locus 20q13.33 is associated with HE, and there is a large genetic overlap between HE and AD.
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Dermatitis Atópica , Eccema , Estudio de Asociación del Genoma Completo , Dermatosis de la Mano , Polimorfismo de Nucleótido Simple , Humanos , Dermatitis Atópica/genética , Masculino , Eccema/genética , Femenino , Dermatosis de la Mano/genética , Adulto , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Persona de Mediana Edad , Genotipo , Sitios Genéticos , Proteínas FilagrinaRESUMEN
BACKGROUND: Quantitative risk assessment (QRA) for skin sensitization is used to derive safe use levels of sensitising fragrance ingredients in products. Post-marketing surveillance of the prevalence of contact allergy to these ingredients provides relevant data to help evaluate the performance of these measures. OBJECTIVES: To determine a suitable patch test concentration for five fragrance materials that had hitherto not been tested on a regular basis. These concentrations are then to be used in a surveillance study with patch testing consecutive patients over an extended monitoring period. MATERIALS AND METHODS: Furaneol, CAS.3658-77-3; trans-2-hexenal, CAS.6728-26-3; 4,8-dimethyl-4,9-decadienal, CAS.71077-31-1; longifolene, CAS.475-20-7; benzaldehyde, CAS.10052-7, were patch tested with other fragrance allergens in four clinics. Patch testing was conducted in three rounds, starting with the lowest concentrations of the five ingredients. The doses were increased in the subsequent rounds if no late-appearing positive reactions and virtually no irritant reactions were reported. RESULTS: Overall, 373 patients were tested. No positive allergic reaction was reported to the five ingredients. Patch test results of other fragrance allergens are reported. CONCLUSIONS: The highest test concentrations are each considered safe for patch testing consecutive patients. Further surveillance based on these preparations will evaluate the hypothesis that QRA-driven consumer product levels of these fragrances can prevent sensitization.
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Alérgenos , Dermatitis Alérgica por Contacto , Pruebas del Parche , Perfumes , Humanos , Pruebas del Parche/métodos , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/diagnóstico , Perfumes/efectos adversos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Alérgenos/efectos adversos , Alérgenos/administración & dosificación , Anciano , Medición de Riesgo , Adulto Joven , Adolescente , Vigilancia de Productos ComercializadosRESUMEN
BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results for the treatment of hand eczema in other studies. OBJECTIVES: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular hand eczema or chronic fissured hand eczema) who have an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable. METHODS: In this 16-week, randomized, double-blind, placebo-controlled proof-of-concept phase IIb trial, patients with severe CHE were randomized 2 : 1 to dupilumab 300â mg or placebo subcutaneously every 2 weeks. Patients visited the outpatient clinic at the initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary endpoint was the proportion of patients achieving at least a 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339). RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab n = 20, placebo n = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group {95% [95% confidence interval (CI) 73.1-99.7] vs. 33% [95% CI 9.0-69.1]}. Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus Numerical Rating Scale compared with placebo [-66.5 ± 10.7 (95% CI -88.6 to -44.5) vs. -25.3 ± 17.0 (95% CI -60.1-9.4)]. Adverse events were similar for the dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug. CONCLUSIONS: Dupilumab was efficacious and well tolerated. Larger studies of longer duration are needed to provide more evidence on the -efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or aetiological -diagnoses.
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Dermatitis Atópica , Eccema , Adulto , Humanos , Alitretinoína/efectos adversos , Anticuerpos Monoclonales Humanizados , Eccema/tratamiento farmacológico , Eccema/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Resultado del Tratamiento , Método Doble Ciego , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Limited research has been conducted on the measurement properties of the Recap of atopic eczema (RECAP) questionnaire, particularly in relation to interpretability. OBJECTIVES: To investigate the validity, reliability, responsiveness and interpretability of the Dutch RECAP in adults with atopic dermatitis (AD). METHODS: We conducted a prospective study in a Dutch tertiary hospital, recruiting adults with AD between June 2021 and December 2022. Patients completed the RECAP questionnaire, reference instruments and anchor questions at the following three timepoints: baseline, after 1-3â days and after 4-12 weeks. Hypotheses testing was used to investigate single-score validity and change-score validity (responsiveness). To assess reliability, both standard error of measurement (SEMagreement) and intraclass correlation coefficient (ICCagreement) were reported. To assess the interpretability of single scores, bands for eczema control were proposed. To investigate the interpretability of change scores, both smallest detectable change (SDC) and minimally important change (MIC) scores were determined. To estimate the MIC scores, four different anchor-based methods were employed: the mean change method, 95% limit cut-off point, receiver operating characteristic curve and predictive modelling. RESULTS: In total, 200 participants were included (57.5% male sex, mean age 38.5â years). Of the a priori hypotheses, 82% (single-score validity) and 59% (responsiveness) were confirmed. Known-group analyses showed differences in the RECAP scores between patient groups based on disease severity and impairment of the quality of life. The SEMagreement was 1.17 points and the ICCagreement was 0.988. The final banding was as follows: 0-1 (completely controlled); 2-5 (mostly controlled); 6-11 (moderately controlled); 12-19 (a little controlled); 20-28 (not at all controlled). Moreover, a single cut-off point of ≥ 6 was determined to identify patients whose AD is not under control. The SDC was 3.2 points, and the MIC value from the predictive modelling was 3.9 points. Neither floor nor ceiling effects were observed. CONCLUSIONS: The RECAP has good single-score validity, moderate responsiveness and excellent reliability. This study fills a gap in the interpretability of the RECAP. Our results indicate a threshold of ≥ 6 points to identify patients whose AD is 'not under control', while an improvement of ≥ 4 points represents a clinically important change. Given its endorsement by the Harmonising Outcome Measures for Eczema initiatives, the results of this study support the integration of RECAP into both routine clinical practice and research settings.
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Dermatitis Atópica , Eccema , Adulto , Humanos , Masculino , Femenino , Dermatitis Atópica/diagnóstico , Calidad de Vida , Estudios Prospectivos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Eccema/diagnósticoRESUMEN
BACKGROUND: Limited data are available regarding patient-centred dosing of dupilumab for atopic dermatitis (AD) in daily practice. OBJECTIVES: To evaluate our patient-centred dupilumab dosing regimen in daily practice, to assess prognostic factors for successful tapering and to estimate medication-related cost savings. METHODS: This prospective multicentre study included adult patients with AD, participating in the BioDay registry, treated with dupilumab for ≥ 1.3â years. Interval prolongation was considered in the case of dupilumab standard dose for ≥ 1â year and persistent controlled AD [Eczema Area and Severity Index (EASI) ≤ 7; ≥ 6â months]. Primary endpoints were the mean EASI and Numeric Rating Scale (NRS)-pruritus after the start of tapering. Prognostic factors for successful tapering were analysed with logistic regression and a cost-savings analysis was performed. RESULTS: A total of 595 patients were included, of whom 401 patients [mean EASI 2.5 (SD 2.3); NRS-pruritus of 2.4 (SD 1.9) at the start of tapering] prolonged their dupilumab interval. In 83.3% of these patients tapering was successful; most patients used dupilumab every 3 or 4 weeks (Q3W/Q4W). A significant small increase was observed for EASI (highest mean 3.5) and NRS-pruritus (highest mean 3.2) (P < 0.001); however, scores remained low. Predicting successful tapering showed nonsignificant odds ratios for all incorporated variables. The estimated cost savings was 3 977 033.98 for 401 patients between January 2019 and June 2022. CONCLUSIONS: This study showed successful tapering of dupilumab in 83.3% of patients with AD who attempted tapering, while maintaining controlled disease and with the majority using Q3W/Q4W. Interval prolongation can be beneficial both for the patient and from a socio-economic perspective.
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Dermatitis Atópica , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Estudios Prospectivos , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Prurito/tratamiento farmacológico , Método Doble CiegoRESUMEN
There is a lack of knowledge concerning loneliness and psychiatric disorders other than anxiety and depression in patients with atopic dermatitis. This cross-sectional study was conducted within the Lifelines Cohort Study, in the Netherlands, by sending an atopic dermatitis questionnaire to adult participants (n = 135,950) in 2020. Psychiatric disorders were measured with a self-reported question and validated instrument (Mini International Neuropsychiatric Interview; M.I.N.I.), and loneliness was assessed with the validated 6-item De Jong Gierveld Loneliness Scale. In total, 56,896 subjects (mean age 55.8 years, 39.7% males) were included. Atopic dermatitis showed positive associations with self-reported chronic fatigue syndrome, burnout, depression, social phobia, panic disorder, attention deficit hyperactivity disorder, and eating disorder in the participants' lifetimes. Based on the M.I.N.I., atopic dermatitis was positively associated with panic disorder and at least 1 anxiety disorder. In addition, subjects with atopic dermatitis were more likely to experience loneliness compared with those without atopic dermatitis. These associations were observed only in the moderate-to-severe, but not mild, atopic dermatitis group. This study raises awareness that a significant proportion of adults with atopic dermatitis feel lonely and are affected by several psychiatric disorders, especially those severely affected by atopic dermatitis. Further studies are required to evaluate if interdisciplinary care, such as the collaboration between dermatologists and psychiatrists, could optimize medical care for this vulnerable patient group.
Asunto(s)
Dermatitis Atópica , Trastornos Mentales , Masculino , Adulto , Humanos , Persona de Mediana Edad , Femenino , Soledad , Estudios de Cohortes , Estudios Transversales , Depresión/diagnóstico , Depresión/epidemiología , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/epidemiología , Ansiedad/diagnóstico , Ansiedad/epidemiología , Trastornos de AnsiedadRESUMEN
BACKGROUND: Hand eczema (HE) is a common skin disease characterized by itch, pain and visible skin changes such as fissures, erythema and vesicles. It is not yet clear which outcome domains are most important for patients. The Hand Eczema Core Outcome Set (HECOS) initiative is developing a consented set of core domains and suitable measurement instruments for the future application in all HE trials. This includes an online Delphi survey about core domains, which requires a 'Long List' of all domains that might be important to measure. OBJECTIVES: To compile a 'Long List' of candidate outcome domains for therapeutic HE trials with suggestions from patients and experts. METHODS: First, 60 patients with chronic HE were interviewed at seven study sites in Croatia, Denmark, Germany, the Netherlands and Spain. Patients were asked about domains that were important from their perspectives. Second, 185 HE experts were invited by email to complete an online survey. With an open question, they were asked to suggest up to six domains. RESULTS: Suggestions were provided by 58 patients and 82 experts. Most patients and experts suggested to measure the domains 'signs', 'symptoms' and 'HE-related quality of life'. Specifically, >25% of patients said that less itch, pain or fissures indicated a successful treatment. Among experts, >25% suggested 'itch' and 'ability to work' as core sub-domains. Further outcomes from the domains 'HE control over time', 'patient-reported treatment experience' and 'skin barrier function' were mentioned. CONCLUSION: 'Itch' was rated high among patients with HE and professional HE experts. While patients emphasized fissures as important, experts underlined the ability to work. This investigation allowed us to define a 'Long List' of 7 candidate outcome domains with 58 sub-domains. From this list, a panel of stakeholders will select core domains during an online Delphi survey.
Asunto(s)
Eccema , Calidad de Vida , Humanos , Eccema/tratamiento farmacológico , Prurito/tratamiento farmacológico , Dolor , Predicción , Técnica Delphi , Resultado del TratamientoRESUMEN
BACKGROUND: Real-world data on the effectiveness of upadacitinib on atopic dermatitis (AD), hand eczema (HE) and HE in the context of AD are limited. OBJECTIVES: To evaluate the effectiveness and safety of upadacitinib on AD and on HE in patients with AD. METHODS: This prospective observational cohort study includes clinical outcomes: Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Hand Eczema Severity Index (HECSI), Photographic guide; and PROMs: average pruritus and pain Numeric Rating Scale (NRS) score of the past week, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Eczema, Dermatology Life Quality Index (DLQI), Atopic Dermatitis Control Tool (ADCT), Patient Global Assessment of Disease (PGAD), Quality Of Life Hand Eczema Questionnaire (QOLHEQ) at baseline, Week 4, and Week 16 of upadacitinib-treated patients. Adverse events were monitored during each visit. RESULTS: Thirty-eight patients were included, of which 32 patients had HE. At Week 16, EASI-75 was achieved by 50.0%. Absolute cutoff score NRS-pruritus ≤4 was reached by 62.5%, POEM ≤7 by 37.5%, DLQI ≤5 by 59.4%, ADCT <7 by 68.8%, and PGAD rating of at least 'good' by 53.1%. HECSI-75 was achieved by 59.3% and (almost) clear on the Photographic guide by 74.1%. The minimally important change in QOLHEQ was achieved by 57.9%. Sub-analysis in patients with concomitant irritant contact dermatitis showed no differences. Safety analysis showed no new findings compared to clinical trials. CONCLUSIONS: Upadacitinib can be an effective treatment for patients with AD and concomitant HE in daily practice. Future studies should focus on the effectiveness of upadacitinib on chronic HE, especially on the different etiological subtypes of HE, including HE in non-atopic individuals.
Asunto(s)
Dermatitis Alérgica por Contacto , Dermatitis Atópica , Eccema , Humanos , Dermatitis Atópica/complicaciones , Calidad de Vida , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Dermatitis Alérgica por Contacto/complicaciones , Eccema/tratamiento farmacológico , Prurito , Resultado del Tratamiento , Sistema de RegistrosRESUMEN
The European baseline series was last updated in 2019. This article discusses the reasoning behind a further iteration of the series for 2023.
Asunto(s)
Dermatitis Alérgica por Contacto , Humanos , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/etiología , Alérgenos , Pruebas del Parche , Europa (Continente)RESUMEN
BACKGROUND: Occupational skin diseases have led the occupational disease statistics in Europe for many years. Especially occupational allergic contact dermatitis is associated with a poor prognosis and low healing rates leading to an enormous burden for the affected individual and for society. OBJECTIVES: To present the sensitization frequencies to the most relevant allergens of the European baseline series in patients with occupational contact dermatitis (OCD) and to compare sensitization profiles of different occupations. METHODS: The data of 16 022 patients considered having OCD after patch testing within the European Surveillance System on Contact Allergies (ESSCA) network between January 2011 and December 2020 were evaluated. Patients (n = 46 652) in whom an occupational causation was refuted served as comparison group. RESULTS: The highest percentages of OCD were found among patients working in agriculture, fishery and related workers, metal industry, chemical industry, followed by building and construction industry, health care, food and service industry. Sensitizations to rubber chemicals (thiurams, carbamates, benzothiazoles) and epoxy resins were associated with at least a doubled risk of OCD. After a decline from 2014 onwards, the risks to acquire an occupation-related sensitization to methyl(chloro)isothiazolinone (MCI/MI) and especially to methylisothiazolinone (MI) seem to increase again. Sensitization rates to formaldehyde were stable, and to methyldibromo glutaronitrile (MDBGN) slightly decreasing over time. CONCLUSIONS: Among allergens in the European Baseline Series, occupational relevance is most frequently attributed to rubber accelerators, epoxy resins and preservatives.
Asunto(s)
Dermatitis Alérgica por Contacto , Dermatitis Profesional , Humanos , Dermatitis Alérgica por Contacto/etiología , Pruebas del Parche/efectos adversos , Goma , Resinas Epoxi , Dermatitis Profesional/etiología , Alérgenos , BenzotiazolesRESUMEN
BACKGROUND: At present, no real-world studies are available on different dupilumab dosing regimens in controlled atopic dermatitis (AD). The aim of this study was to clinically evaluate a patient-centered dupilumab dosing regimen in patients with controlled AD and to relate this to serum drug levels and serum biomarkers. METHODS: Ninety adult AD patients from the prospective BioDay registry were included based on their dupilumab administration interval according to a predefined patient-centered dosing regimen. Group A (n = 30) did not fulfill the criteria for interval prolongation and continued using the standard dupilumab dosage (300 mg/2 weeks), group B (n = 30) prolonged dupilumab interval with 50% (300 mg/4 weeks), and group C (n = 30) prolonged dupilumab interval with 66%-75% (300 mg/6-8 weeks). AD severity score, patient-reported outcomes, serum dupilumab levels, and serum biomarkers were analyzed over time. RESULTS: Disease severity scores did not significantly change over time during the tapering period in any of the groups. In groups B and C, the Numeric Rating Scale (NRS)-pruritus temporarily significantly increased after interval prolongation but remained low (median NRS-pruritus≤4). Median dupilumab levels remained stable in group A (standard dosage), but significantly decreased in groups B and C (24.1 mg/L (IQR = 17.1-45.6); 12.5 mg/L (IQR = 1.7-22.3)) compared with the levels during the standard dosage (88.2 mg/L [IQR = 67.1-123.0, p < .001]). Disease severity biomarker levels (CCL17/CCL18) remained low in all study groups during the whole observation period. CONCLUSIONS: This study showed that dose reduction was successful in a subgroup of patients with controlled AD by using a patient-centered dosing regimen. These patients showed stable low disease activity and low severity biomarkers over time.