The association between wet work and hand eczema in the Dutch general population: Application of a job exposure matrix to the lifelines cohort study.

BACKGROUND: Studies on wet work and hand eczema (HE) frequently rely solely on self-reports regarding wet work. OBJECTIVES: To assess the association between wet work and moderate-to-very-severe HE, within the Dutch general population, by using a (sex-specific) job exposure matrix (JEM). METHODS: Within the Lifelines Cohort Study, participants with self-reported moderate-to-very-severe HE at worst in the past year were linked to data from the Danish (sex-specific) wet work JEM, a tool that links occupations with wet work indices (including duration and probability of glove use, wet hands and total wet work for at least 2 and 4 h/working day). RESULTS: In total, 56 978 (41.9%) participants were included. The multivariate binary logistic regression analyses showed significant associations between all facets of wet work and moderate-to-very-severe HE. When using the sex-specific JEM, significant associations were found in females, but not in males. CONCLUSIONS: This study is the first to use a wet work-specific JEM in a general population sample, and found positive associations between wet work and HE. The sex-specific findings should be interpreted with caution, due to limitations inherent in using a JEM, and should be further explored with observational studies, with a focus on duration, frequency, and exposure type.

Long-Term Effectiveness and Reasons for Discontinuation of Dupilumab in Patients With Atopic Dermatitis.

Importance: Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice. Objective: To evaluate clinical effectiveness and reasons for discontinuation of dupilumab treatment in children, adults, and older adults with AD with up to 5 years of treatment in daily practice. Design, Setting, and Participants: This prospective multicenter cohort study was conducted using the BioDay registry (4 academic and 10 nonacademic hospitals in the Netherlands) to identify patients with AD of all ages who were treated with dupilumab between October 2017 and December 2022. Main Outcomes and Measures: Clinical effectiveness was evaluated by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and numeric rating scale (NRS) for pruritus, stratified by children (<18 years), adults (18-64 years), and older adults (≥65 years). In addition, time to response, treatment responders, EASI subscores, second treatment episodes, and thymus- and activation-related chemokine and eosinophil levels were assessed. For patients who discontinued dupilumab, the reason for discontinuation was evaluated. Results: In total, 1286 patients with AD (median [IQR] age, 38 [26-54] years; 726 [56.6%] male) were treated with dupilumab, including 130 children, 1025 adults, and 131 older adults. The median (IQR) follow-up time was 87.5 (32.0-157.0) weeks. Most patients maintained controlled AD, with EASI of 7 or lower and NRS for pruritus of 4 or lower varying between 78.6% and 92.3% and 72.2% and 88.2% for up to 5 years of treatment, respectively, while up to 70.5% of all patients prolonged the dosing interval to mostly 300 mg every 3 or 4 weeks. Mean EASI and NRS for pruritus were 2.7 (95% CI, 1.2-4.2) and 3.5 (95% CI, 2.7-4.3), respectively, after 5 years of treatment. Statistically significant differences between age groups were found over time for EASI and IGA; however, differences were rather small (week 52: EASI, 0.3-1.6; IGA, 0.12-0.26). No statistically significant differences between age groups were found for NRS for pruritus. Median thymus- and activation-related chemokine levels considerably decreased from 1751 pg/mL (95% CI, 1614-1900 pg/mL) to 390 pg/mL (95% CI, 368-413 pg/mL) after 6 months of treatment and remained low. Median eosinophil levels temporarily increased up to week 16, with a subsequently statistically significant decrease over time. In total, 306 patients (23.8%) discontinued dupilumab after a median (IQR) of 54.0 (29.0-110.00) weeks, with adverse events among 98 patients (7.6%) and ineffectiveness among 85 patients (6.6%) as the most frequently reported reasons. Forty-one patients (3.2%) restarted dupilumab, and most of these patients recaptured response. Conclusions and Relevance: In this cohort study with up to 5 years of follow-up, dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered to a dosing interval of every 3 or 4 weeks. Treatment was discontinued in 23.8% of patients mainly due to adverse events and/or ineffectiveness.

A genome-wide association study of hand eczema identifies locus 20q13.33 and reveals genetic overlap with atopic dermatitis.

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.

Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

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.

Health literacy in adult patients with atopic dermatitis: A cross-sectional study.

Background: Health literacy (HL) is defined as the degree to which individuals have the capacity to obtain, process, and understand health information and services needed to make appropriate health decisions. Patients with limited HL are less likely to manage chronic diseases appropriately. Objective: We sought to assess the prevalence of limited HL in patients with atopic dermatitis (AD) and its association with other patient-reported outcomes. Methods: A cross-sectional questionnaire-based study was conducted at a tertiary referral center for AD. Patients diagnosed with AD by a dermatologist between 2019 and 2021 were identified from medical records. Perception-based HL was assessed by the European Health Literacy Survey Questionnaire 16 and performance-based HL by the Newest Vital Sign. Patients completed the Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and Atopic Dermatitis Control Tool to measure AD severity, quality of life, and AD disease control, respectively. Results: In total, 322 patients were included (response rate, 48.3%). On the basis of the European Health Literacy Survey Questionnaire 16, 32.4% had limited HL (8.4% inadequate and 24.0% problematic), which was associated with impaired quality of life. According to the Newest Vital Sign, 20.3% had inadequate HL, which was associated with older age. Conclusions: Up to one-third of the patients with AD showed signs of limited HL, which was associated with impaired health-related quality of life and older age. Further research should evaluate the influence of inadequate HL on health outcomes and focus on strategies to improve organizational HL to eventually enhance patient-centered care.

Hand eczema-related presenteeism and sickness absence: A cross-sectional population-based study.

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.

Real-world Experience of Abrocitinib Treatment in Patients with Atopic Dermatitis and Hand Eczema: Up to 28-week Results from the BioDay Registry.

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.

Beyond Anxiety and Depression: Loneliness and Psychiatric Disorders in Adults with Atopic Dermatitis.

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.

Validity, reliability, responsiveness and interpretability of the Recap of atopic eczema (RECAP) questionnaire.

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 1-3 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 38.5 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.

Successful tapering of dupilumab in patients with atopic dermatitis with low disease activity: a large pragmatic daily practice study from the BioDay registry.

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 ≥ 1.3 years. Interval prolongation was considered in the case of dupilumab standard dose for ≥ 1 year and persistent controlled AD [Eczema Area and Severity Index (EASI) ≤ 7; ≥ 6 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.

Limited Health Literacy and Its Associated Health Outcomes Among Adults With at Least 2 Atopic Diseases.

BACKGROUND: Health literacy (HL) is essential for patients with multiple atopic diseases to improve their health, given the complexity of their disease and treatment regimens. OBJECTIVE: To estimate the proportion of adults with multiple atopic diseases (at least 2 of atopic dermatitis, asthma, allergic rhinitis, and food allergy) in the Dutch general population and to evaluate the prevalence of limited HL, and its association with socioeconomic status (SES), lifestyle factors, and health-related quality of life (HR-QoL) in this patient population. METHODS: This cross-sectional study was conducted within the Lifelines Cohort Study via sending an add-on digital questionnaire, including (among others) questions on atopic dermatitis, to all adult participants (n = 135,950) between February and May 2020. Data on asthma, allergic rhinitis, lifestyle factors, HR-QoL, and SES were extracted from baseline assessment between 2006 and 2013. Functional, communicative, and critical HL were measured by validated items from Chew and the Dutch Functional Communicative and Critical Health Literacy questionnaires between 2012 and 2016. Food allergy was measured by the Food Allergy Questionnaire between 2014 and 2016. RESULTS: In total, 11.8% of the overall study population reported ever having multiple atopic diseases; of those, 23.6% reported having limited functional HL, with a higher prevalence among those with a low SES. Limited functional HL showed positive associations with smoking, obesity, chronic stress, a low diet quality, and decreased HR-QoL among subjects with multiple atopic diseases. CONCLUSIONS: We identified an HL deficit, and its association with a low SES and poor health outcomes among patients with multiple atopic diseases. Further research is warranted to utilize a more extensive assessment to measure HL and include more health outcomes, such as treatment adherence and disease control.

Experiences from daily practice of upadacitinib treatment on atopic dermatitis with a focus on hand eczema: Results from the BioDay registry.

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.

Which outcomes should be measured in hand eczema trials? Results from patient interviews and an expert survey.

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.

Dupilumab in daily practice for the treatment of pediatric atopic dermatitis: 28-week clinical and biomarker results from the BioDay registry.

BACKGROUND: Dupilumab has proven to be an effective and safe treatment for atopic dermatitis (AD) in pediatric patients in clinical trials. However, few daily practice studies are available. The aim of this study is to evaluate the effect of 28 weeks dupilumab treatment on effectiveness, safety, and serum biomarkers in pediatric patients with moderate-to-severe AD in daily practice. METHODS: Patients visited the outpatient clinic at baseline, 4, 16, and 28 weeks of treatment. Disease severity was assessed by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Numeric Rating Scale (NRS)-pruritus and -pain, and the Patient-Oriented Eczema Measure (POEM). Side effects were evaluated. Nineteen severity-associated serum biomarkers were measured. Predicted-EASI (p-EASI) was calculated. RESULTS: Sixty-one patients were included. Respectively 75.4%, 49.2%, and 24.6% reached EASI-50, EASI-75, and EASI-90 and 36.1% achieved an IGA-score (almost) clear. Improvement of ≥4 points on POEM, NRS-pruritus, and NRS-pain was reached by 84.7%, 45.3%, and 77.4%, respectively. Most reported side effects were conjunctivitis (n = 10) and headache (n = 4). Biomarkers TARC, PARC, periostin, sIL-2Ra, and eotaxin-3 significantly decreased during treatment. The p-EASI showed a significant correlation with disease severity. CONCLUSION: Dupilumab treatment significantly improved disease severity and disease-associated symptoms and decreased severity-associated serum biomarkers in pediatric AD patients in daily practice.

Daily Practice Experience of Baricitinib Treatment for Patients with Difficult-to-Treat Atopic Dermatitis: Results from the BioDay Registry.

Clinical trials have shown that baricitinib, an oral selective Janus kinase 1/2 inhibitor, is effective for the treatment of moderate-to-severe atopic dermatitis. However, daily practice data are limited. Therefore, this multicentre prospective study evaluated the effectiveness and safety of 16-weeks' treatment with baricitinib in adult patients with moderate-to-severe atopic dermatitis in daily practice. A total of 51 patients from the BioDay registry treated with baricitinib were included and evaluated at baseline and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed using clinician- and patient-reported outcome measurements. Adverse events and laboratory assessments were evaluated at every visit. At week 16, the probability (95% confidence interval) of achieving Eczema Area and Severity Index ≤ 7 and numerical rating scale pruritus ≤ 4 was 29.4% (13.1-53.5) and 20.5% (8.8-40.9), respectively. No significant difference in effectiveness was found between dupilumab non-responders and responders. Twenty-two (43.2%) patients discontinued baricitinib treatment due to ineffectiveness, adverse events or both (31.4%, 9.8% and 2.0%, respectively). Most frequently reported adverse events were nausea (n = 6, 11.8%), urinary tract infection (n = 5, 9.8%) and herpes simplex infection (n = 4, 7.8%). In conclusion, baricitinib can be an effective treatment option for moderate-to-severe atopic dermatitis, including patients with non-responsiveness on dupilumab. However, effectiveness of baricitinib is heterogeneous, which is reflected by the high discontinuation rate in this difficult-to-treat cohort.

Dupilumab Drug Survival and Associated Predictors in Patients With Moderate to Severe Atopic Dermatitis: Long-term Results From the Daily Practice BioDay Registry.

Importance: Long-term data on dupilumab drug survival in patients with atopic dermatitis (AD) are scarce. Furthermore, little is known about the factors associated with drug survival of dupilumab in AD. Objective: To describe the drug survival of dupilumab in patients with AD and to identify associated predictors. Design, Setting, and Participants: This cohort study was based on data from the multicenter prospective daily practice BioDay registry, in which 4 university and 10 nonuniversity hospitals in the Netherlands participated. Analysis included patients (age ≥18 years) participating in the BioDay registry with a follow-up of at least 4 weeks. The first patient treated with dupilumab was recorded in the BioDay registry in October 2017; data lock took place in December 2020, and data analysis was performed from October 2017 to December 2020. Main Outcomes and Measures: Drug survival was analyzed by Kaplan-Meier survival curves and associated characteristics by using univariate and multivariate Cox regression analysis. Results: A total of 715 adult patients with AD (mean [SD] age, 41.8 [16.0] years; 418 [58.5%] were male) were included with a 1-year, 2-year, and 3-year overall dupilumab drug survival of 90.3%, 85.9%, and 78.6%, respectively. Characteristics associated with shorter drug survival owing to ineffectiveness were the use of immunosuppressant drugs at baseline (hazard ratio [HR], 2.64; 95% CI, 1.10-6.37) and being a nonresponder at 4 weeks (HR, 8.68; 95% CI, 2.97-25.35). Characteristics associated with shorter drug survival owing to adverse effects were the use of immunosuppressant drugs at baseline (HR, 2.69; 95% CI, 1.32-5.48), age 65 years or older (HR, 2.94; 95% CI, 1.10-7.87), and Investigator Global Assessment score of very severe AD (HR, 3.51; 95% CI, 1.20-10.28). Conclusions and Relevance: This cohort study demonstrated a good overall 1-year, 2-year, and 3-year dupilumab drug survival. Patients using immunosuppressive therapy at baseline and those with an absence of treatment effect at week 4 tended to discontinue treatment owing to ineffectiveness more frequently. Using immunosuppressant drugs at baseline, older age, and Investigator Global Assessment score of very severe AD were characteristics associated with an increased risk for discontinuation owing to adverse effects. These data provide more insight and new perspectives regarding dupilumab treatment in AD and can contribute to the optimization of patient outcomes.

Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis.

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.

Association between moderate to severe atopic dermatitis and lifestyle factors in the Dutch general population.

BACKGROUND: Studies on the association between severity of atopic dermatitis (AD) and lifestyle factors in adults have not been conducted in the Netherlands to date. AIM: To explore the association between moderate to severe AD and lifestyle factors in adults in the Dutch general population. METHODS: We conducted this cross-sectional study within the Lifelines Cohort Study by sending a digital AD questionnaire to 135 950 adults in 2020. We extracted data on lifestyle factors from baseline, collected between 2006 and 2013. We analysed the association between lifestyle factors and presence of AD of any severity and of moderate to severe AD, using binary logistic regression and linear regression models. RESULTS: We enrolled 56 896 participants (mean age 55.8 years, 39.7% males). The lifetime prevalence of self-reported physician-diagnosed AD was 9.1%, and the point prevalence of any AD and of moderate to severe AD was 3.3% and 2.3%, respectively. We found that moderate to severe AD was associated with smoking habit of > 15 pack-years, alcohol consumption of > 2 drinks per day, chronic stress, Class I obesity, and both shorter and longer sleep duration. Moreover, we found dose-response associations with increases in smoking pack-years and level of chronic stress. We observed no associations with abdominal obesity, physical activity, diet quality or a vegetarian/vegan diet. CONCLUSION: We found associations between moderate to severe AD and some modifiable lifestyle factors. Our findings indicate that more screening and counselling for lifestyle factors, particularly smoking, alcohol use, stress, obesity and sleep disturbances, appears warranted in patients with moderate to severe AD. Further longitudinal studies are required to better characterize the direction of these associations and to develop strategies for prevention.

Lifestyle factors and hand eczema: A systematic review and meta-analysis of observational studies.

Evidence regarding the association between lifestyle factors and hand eczema is limited.To extensively investigate the association between lifestyle factors (smoking, alcohol consumption, stress, physical activity, body mass index, diet, and sleep) and the prevalence, incidence, subtype, severity, and prognosis of hand eczema, a systematic review and meta-analysis were conducted in accordance with the Meta-analysis Of Observational Studies in Epidemiology consensus statement. MEDLINE, Embase, and Web of Science were searched up to October 2021. The (modified) Newcastle-Ottawa Scale was used to judge risk of bias. Quality of the evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation approach. Eligibility and quality were blindly assessed by two independent investigators; disagreements were resolved by a third investigator. Data were pooled using a random-effects model, and when insufficient for a meta-analysis, evidence was narratively summarized. Fifty-five studies were included. The meta-analysis (17 studies) found very low quality evidence that smoking is associated with a higher prevalence of hand eczema (odds ratio 1.18, 95% confidence interval 1.09-1.26). No convincing evidence of associations for the other lifestyle factors with hand eczema were found, mostly due to heterogeneity, conflicting results, and/or the limited number of studies per outcome.