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Background: Hand eczema is a common condition; it is often chronic and can be difficult to treat. Cyclosporine is used off-label to treat severe hand eczema; however, the evidence for this treatment is scarce. Objective: To examine the drug survival of cyclosporine in a daily practice cohort of patients with chronic hand eczema. Methods: This retrospective daily use study included hand eczema patients who were treated with cyclosporine between 01-06-1999 and 01-06-2014 in two Dutch university hospitals. Patient and treatment characteristics were retrospectively collected from medical charts. First treatment episodes were analysed by means of Kaplan-Meier drug survival curves. Possible determinants of drug survival were analysed by Cox regression models. Treatment effectiveness was analysed with a retrospective physician's global assessment. Results: A total of 102 patients were treated with cyclosporine. The median drug survival rate was 0.86 years (10.3 months). The overall drug survival rate after 6 months, 1, 2 and 3 years were 61.7%, 45.2%, 18.6% and 13.9% respectively. Main reasons for discontinuation were adverse events, especially early in treatment, and ineffectiveness. After 3 months, a good response to treatment was recorded in 62.9% of the patients. Conclusion: Cyclosporine had a median drug survival of 10.3 months. Especially patients with recurrent vesicular hand eczema showed a good treatment response. [ABSTRACT FROM AUTHOR]

Background Long-term data of ciclosporin A (CsA) treatment in daily practice in patients with severe atopic dermatitis ( AD) are lacking. Objectives To perform a detailed analysis of drug survival, which is the length of time a patient continues to take a drug, for CsA in a long-term daily practice cohort of patients with AD. The secondary objective was to identify determinants of drug survival. Methods Data were extracted from a retrospective cohort of patients treated with CsA for AD. Drug survival was analysed using Kaplan-Meier survival curves. Determinants of drug survival were analysed using uni- and multivariate Cox regression analyses with backward selection. Results In total, 356 adult patients were analysed (386 patient-years). The overall drug survival rates were 34%, 18%, 12% and 4% after 1, 2, 3 and 6 years, respectively. Reasons for discontinuation were controlled AD (26·4%), side-effects (22·2%), ineffectiveness (16·3%), side-effects plus ineffectiveness (6·2%) or other reasons (11·0%). Older age was associated with a decreased drug survival related to controlled AD [hazard ratio ( HR) 0·91]. Older age was also associated with a decreased drug survival related to side-effects ( HR 1·14). An intermediate-to-high starting dose (> 3·5-5·0 mg kg−1 daily) was associated with an increased drug survival related to ineffectiveness ( HR 0·63). Conclusions This is the first study on drug survival for CsA treatment in AD. Older age was associated with decreased drug survival related to controlled AD and side-effects. An intermediate-to-high starting dose was associated with an increased drug survival related to ineffectiveness. [ABSTRACT FROM AUTHOR]

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.

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., Competing Interests: Conflicts of interest C.M. Boesjes is a speaker for AbbVie and Eli Lilly. L.S. Spekhorst is a speaker for AbbVie. I.M. Haeck is a consultant, advisory board member, and/or speaker for Sanofi and Regeneron Pharmaceuticals, LEO Pharma, AbbVie, Janssen, and Eli Lilly. L.F. van der Gang is a speaker for AbbVie. L.P. van der Rijst is a speaker for AbbVie. R.A. Tupker is an advisory board member of Leo Pharma, Eli Lilly, and Novartis. K.Politiek was an advisory board member and/or speaker for AbbVie, LEO Pharma, Novartis, and Sanofi. W. Touwslager is an advisor, consultant, and speaker for Sanofi, Leo Pharma, AbbVie, and Novartis. WA Christoffers is an advisory board member of Leo Pharma. M. de Graaf is a consultant, advisory board member, and/or speaker for AbbVie, Almiral, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi. M.S. de Bruin-Weller is a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Aslan, Amgen, Eli Lilly, Galderma, Janssen, Leo Pharma, Pfizer, Regeneron, and Sanofi. M.L.A. Schuttelaar is an advisor, consultant, speaker, and/or investigator for AbbVie, Pfizer, LEO Pharma, Regeneron, Sanofi, Eli Lilly, and Galderma. She has received grants from Regeneron, Sanofi, Novartis, and Pfizer., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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.

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., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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.

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., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Hyperkeratotic hand eczema (HHE) is a typical clinical hand eczema subtype with a largely unknown pathophysiology., Objective: To investigate histopathology, expression of keratins (K), epidermal barrier proteins, and adhesion molecules in HHE., Methods: Palmar skin biopsies (lesional and perilesional) were obtained from seven HHE patients and two healthy controls. Moreover, 135 candidate genes associated with palmoplantar keratoderma were screened for mutations., Results: Immunofluorescence staining showed a significant reduction of K9 and K14 in lesional skin. Upregulation was found for K5, K6, K16, and K17 in lesional skin compared with perilesional and healthy palmar skin. Further, upregulation of involucrin and alternating loricrin staining, both in an extracellular staining pattern, was found. Filaggrin expression was similar in lesional, perilesional, and control skin. No monogenetic mutations were found., Conclusion: Currently, the phenotype of HHE is included in the hand eczema classification system; however, it can be argued whether this is justified. The evident expression of filaggrin and involucrin in lesional skin does not support a pathogenesis of atopic eczema. The upregulation of K6, K16, and K17 and reduction of K9 and K14 might contribute to the underlying pathogenesis. Unfortunately, comparison with hand eczema studies is not possible yet, because similar protein expression studies are lacking., (© 2020 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Recurrent vesicular hand eczema frequently has a chronic course and needs long-term treatment., Objectives: To evaluate health-related quality of life (HRQoL), treatment satisfaction, and adherence in patients with vesicular hand eczema., Methods: Patients using one main treatment for at least three months were included. Data on HRQoL (Quality of Life in Hand Eczema Questionnaire [QOLHEQ]), treatment satisfaction (Treatment Satisfaction Questionnaire for Medication, version II), and treatment adherence (4-item Morisky Medication Adherence Scale) were collected. Univariate and multivariate regression analysis were used to predict variables associated with HRQoL., Results: HRQoL was moderately impaired, with the highest impact in the QOLHEQ subdomain symptoms. Female sex, more severe hand eczema, and lower treatment satisfaction were associated with more impairment in HRQoL. Patients with severe/very severe hand eczema had significant lower "global satisfaction" scores compared with the other severity groups. The "global satisfaction" and treatment adherence in patients using systemic treatment were significantly higher compared with those with only topical treatment., Conclusions: In patients with vesicular hand eczema disease severity affects both HRQoL and treatment satisfaction. Systemic treatment of severe hand eczema could improve the severity and as a result also HRQoL, treatment satisfaction, and medication adherence., (© 2019 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Acitretin has been used off-label for years to treat chronic hand eczema, but acitretin is less often prescribed as alitretinoïne was approved. This study evaluates both retinoids in a daily practice cohort of patients with severe chronic hand eczema in terms of drug survival and reasons for discontinuation. Patients using alitretinoin or acitretin between 01-01-1994 and 01-08-2015 were included in this retrospective daily practice study and analyzed by Kaplan-Meier drug survival curves. Potential determinants were analyzed by Cox regression analyses. Ninety-five patients were treated with alitretinoin and 109 patients with acitretin. The main reasons for discontinuation were adverse events and cleared hand eczema, 29.5 and 27.4% in alitretinoin versus 43.1 and 23.9% in acitretin. Patients with hyperkeratotic hand eczema had most often a good effect of treatment: 68.3% in alitretinoin and 50.7% in acitretin treatment. The drug survival rates of alitretinoin and acitretin after 12, 24, 36, and 52 weeks were 69.3, 45.1, 19.6, 7.0% and 74.3, 45.5, 33.8, 23.2%, respectively. Alitretinoin and acitretin are effective treatment options for patients with hand eczema. However, both treatments were more effective in patients with hyperkeratotic hand eczema. Fewer patients discontinued alitretinoin compared with acitretin due to adverse events., (© 2016 Wiley Periodicals, Inc.)

The individual burden of disease in hand eczema patients is considerable. However, little is known about the socio-economic impact of this disease. The aims of this review were to evaluate the literature on cost-of-illness in hand eczema, and to compose a checklist for future use. The literature was retrieved from the MEDLINE and EMBASE databases up to October 2015. Quality evaluation was based on seven relevant items in cost-of-illness studies. Cost data (direct and indirect) were extracted and converted into euros (2014 price level) by use of the Dutch Consumer Price Index. Six articles were included. The mean annual total cost per patient ranged from €1311 [corrected] to €9792 (direct cost per patient, €521 to €3722; [corrected] and indirect cost per patient, €100 to €6846). Occupational hand eczema patients showed indirect costs up to 70% of total costs, mainly because of absenteeism. A large diversity in hand eczema severity was found between studies. The socio-economic burden of hand eczema is considerable, especially for more severe and/or occupational hand eczema. Absenteeism from paid work leads to a high total cost-of-illness, although disregard of presenteeism often leads to underestimation of indirect costs. Differences in included cost components, the occupational status of patients and hand eczema severity make international comparison difficult. A checklist was added to standardize the approach to cost-of-illness studies in hand eczema., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)