Efficacy and Safety of Benvitimod Compared with Halometasone in Patients with Moderate-to-Severe Chronic Hand Eczema: A Prospective, Single-Center, Parallel-Group, Open-Label Randomized Trial.

IntroductionThe purpose of this study was to assess the efficacy and safety of fractional CO2 laser combined with halometasone cream in patients with moderate-to-severe chronic hand eczema (CHE).MethodsA prospective, single-center, parallel-group, open-label randomized trial including 67 patients with moderate-to-severe CHE was carried out. Patients were randomly assigned to group A (n = 33, fractional CO2 laser once every 4 weeks 1–2 times and halometasone cream twice daily for 8 weeks) or group B (n = 34, halometasone cream alone twice daily for 8 weeks). The primary endpoint was the proportion of patients achieving treatment success at week 12 in each group. Secondary endpoints included differences between groups in the change of hand eczema severity index (HECSI), patient global assessment (PaGA), dermatology life quality index (DLQI), and quality of life in hand eczema questionnaire (QOLHEQ) from baseline to week 12. Relapse rate and adverse effects were also recorded.ResultsA total of 29 patients in each group completed the trial. At week 12, the treatment success rate was 62.1% (18/29) in group A and 27.6% (8/29) in group B (p = 0.009). At week 12, HECSI, PaGA, DLQI, and QOLHEQ all decreased compared with baseline in both groups (p < 0.05). HECSI, DLQI, and QOLHEQ decreased more in group A than group B (p = 0.014, 0.010, and 0.014, respectively), but there was no significant difference in change of PaGA between the two groups (1.0 versus 3.0, p = 0.419). Among patients achieving treatment success, 11.1% (2/18) patients in group A and 50.0% (4/8) patients in group B relapsed at week 24 (p = 0.011). Skin pigmentation was the most common adverse effect.ConclusionsFor patients with moderate-to-severe CHE, fractional CO2 laser combined with halometasone cream is more effective than halometasone cream alone, with few adverse effects.Trial Registration NumberChiCTR2100051948.

Baricitinib treatment of severe chronic hand eczema: Two case reports

The impact of hand eczema (HE) on Health-Related Quality of Life (HRQoL) has only been sparsely studied in a general population setting, and never by use of the disease specific Quality Of Life in Hand eczema Questionnaire (QOLHEQ). To examine the HRQoL of unselected individuals with HE using the QOLHEQ. Further, to provide prevalence estimates of severe and chronic HE (CHE), and to contrast overall health related outcomes between individuals with and without HE. In this nationwide, cross-sectional study a questionnaire covering questions on HE related outcomes, and overall health was sent to a random sample of 100 000 Danish adults via a secure digital mailbox, linked to their unique civil registration numbers. Data on demographic characteristics were retrieved from the civil registration system. Individuals reporting HE, further answered the QOLHEQ and other disease specific questions. The response rate was 42.7% (n = 42 691). Total estimates of lifetime, 1-year and point prevalences of HE were 24.4%, 13.3% and 5.8%. Of individuals reporting a 1-year prevalence, 35.1% reported moderate-severe disease and 82.6% CHE. Individuals with HE were more likely to report less good or poor overall health, and sick leave (any reason), compared to those without. In the 2176 (92.5%) with current HE who completed the QOLHEQ, median QOLHEQ scores corresponded to a moderate impairment of the symptoms and treatment and prevention domains and a slight impairment overall and for the emotions and functioning domains. Factors that were strongly associated with moderate to severe HRQoL impairment included severe, chronic and occupational HE as well as female sex. HE is highly prevalent, bears a considerable burden on society and significantly affects the lives of impacted individuals. Our findings indicate a necessity for targeted prevention aimed at high-risk groups, and support and treatment for those most affected.

Patient-reported outcome measures (PROMs) provide an important complement to physician-assessed clinical outcome measures in dermatologic diseases such as atopic dermatitis (AD) and chronic hand eczema (CHE). AD and CHE are chronic and relapsing inflammatory skin conditions that often co-occur. While both diseases result in various signs and symptoms that are burdensome and can negatively affect patients’ lives, there may be distinct differences in the signs, symptoms, burden, and health-related quality of life (HRQOL) impact of these diseases. The objective of this study was to identify and evaluate PROMs used in studies of AD and CHE. The aim was to explore the assessment of key symptoms and impacts, and identify any gaps in the measures in use. A structured review of the PubMed database was conducted to identify PROMs used or developed for use in AD or CHE. The Dermatology Life Quality Index (DLQI), the Pruritus/Itch Numeric Rating Scale (NRS), the Patient-Oriented Eczema Measure (POEM), and the Quality of Life in Hand Eczema Questionnaire (QOLHEQ) were identified and reviewed in detail. With these measures, the AD and CHE symptoms and impacts most commonly evaluated in the literature include dermatology-related HRQOL in the domains of symptoms and feelings, daily activities, leisure, work and school, personal relationships, and adverse effects; pruritus; sleep disturbance; AD-specific symptoms (dryness, itching, flaking, cracking, bleeding, and weeping/oozing); and CHE-specific symptoms (pain, itch, fissuring, redness, bleeding, and dryness). A review of regulatory labels of drugs approved for AD by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) found that, among the four measures reviewed, the Pruritus NRS was included in the FDA and EMA labels for dupilumab, the DLQI was included in the EMA labels for dupilumab and tacrolimus, and the POEM was included in the EMA label for dupilumab. Key symptoms of AD (e.g. itching, flaking, cracking) and CHE (e.g. pain, itching, fissuring) are increasingly being assessed with PROMs; however, primary endpoints in clinical trials are often based on clinician-reported outcome measures. As therapeutic strategies in dermatology are targeted at specific dermatologic symptoms and diseases affecting specific sites (e.g. CHE), future research should explore patients’ experiences with these symptoms and sites and the changes with treatment that are most meaningful to them.Electronic supplementary materialThe online version of this article (10.1007/s40271-019-00373-y) contains supplementary material, which is available to authorized users.

BackgroundThe hands are a common predilection site of atopic dermatitis (AD). Dupilumab is licensed for the treatment of AD but not for chronic hand eczema (CHE), while CHE is challenging to treat.ObjectivesTo evaluate the long‐term effect of dupilumab on hand eczema (HE) in patients with AD from the BioDay Registry.MethodsA prospective observational study of adult patients with HE, treated for AD with dupilumab. Patients with a HE severity of at least moderate at baseline were considered for analysis. Patients with other concomitantly systemic immunosuppressive treatments were excluded. Clinical effectiveness on HE severity, using the Hand Eczema Severity Index (HECSI) and photographic guide, and health‐related quality of life, using the Quality of Life in Hand Eczema Questionnaire (QOLHEQ), were evaluated.ResultsA total of 72 patients were included. HECSI‐75 was achieved by 54/62 patients (87.1%) and HECSI‐90 by 39/72 (62.9%) at 52 weeks. Based on the photographic guide, 56/62 patients (90.3%) achieved the endpoint of ‘clear’ or ‘almost clear’. Mean QOLHEQ reduction was −63.5% (95% confidence interval −38.23 to −27.41). There was no difference in response between HE subtypes.ConclusionsThe results from this study hold promise for dupilumab to be a suitable treatment option for isolated CHE.

PSY52 PATIENT-REPORTED OUTCOME MEASURES IN ATOPIC DERMATITIS AND CHRONIC HAND ECZEMA IN ADULTS

Background: Health related Quality of Life (HRQOL) is a patient reported outcome (PRO) used to evaluate clinical trials in various diseases. Health economic decisions are often based on HRQOL data, especially where the disease of interest is a chronic non life-threatening condition. Since there is no disease-specific HRQOL instrument to assess the impairments of patients with hand eczema (HE) we set out to develop an instrument to assess HE-specific HRQOL. The development process was done in an international group in order to receive an instrument which works in a culturally equivalent manner in different countries. Here we present the validation study of the German language version of the Quality of Life in hand eczema Questionnaire (QOLHEQ). Methods: The QOLHEQ was assessed up to three times in n = 316 HE patients. To explore construct validity we additionally assessed dermatology-specific (Dermatology Life Quality Index (DLQI) and Skindex-17) and generic (EuroQol -5 Dimensions (EQ -5D) HRQOL-instruments, a physician global assessment (PGA) of the HE and the disease severity as rated by the patient. The psychometric properties of the QOLHEQ were assessed using the Rasch model for each of the four subscales (symptoms, emotions, functioning and treatment/prevention) and a structural equation model to confirm the multi-dimensional structure of the QOLHEQ. We used several indices to test the responsiveness ofthe instrument. The analyses were done using AMOS 20, SPSS 20 and Rumm2030, Results: The study population was aged18 to 81 years (Mean: 46.7, SD 12.9), 45.9% were males. The PGA was normally distributed across the sample. After minor adaptations in the coding of two items all four subscales showed neither violations nor significant misfit to the Rasch model. The data revealed also a good fit to the structural equation model with HRQOL as primary construct and the four subscales as 2nd order factors. As expected the QOLHEQ showed a strong correlation with the dermatology-specific instruments (DLQI: r = 0.75 Skindex-17: r = 0.85) and a medium correlation with the EQ-5D (r =-0.51), the PGA (r = 0.34) and the disease severity reported by the patient (r = 0.59). The sensitivity to change of the QOLHEQ was superior compared with the other HRQOL-instruments as indicated by various responsiveness indices. Discussion: We have successfully developed and validated a diseases-specific HRQOL-instrument for HE. The QOLHEQ consists of 30 items assessing four relevant domains of HRQOL in HE patients and is ready to use in the German version. It's psychometric properties and responsiveness make it superior in assessing HRQOL in HE patients compared to other skin-disease specific or generic instruments. Other language versions (English, Danish, Finish, Japanese, Swedish and Turkish) will be available soon enabling scientists to compare their HRQOL data across countries.

Overall adherence in the treatment of chronic dermatoses is poor. Textbooks state an adherence dependence on galenics. Prospective, randomized, parallel-grouped, single-blinded (investigator), monocentric clinical trial (phase IV) on the adherence to treatment of chronic mild to moderate hand eczema with topical methylprednisolone aceponate (MPA, Advantan®) in different vehicles. Primary objective was the assessment of the adherence depending on vehicle type in patients with chronic hand eczema. Secondary objective was improvement after a 4-week treatment period. Primary Endpoint Adherence is defined as the percentage of patients applying at least aimed daily dose. Prescribed daily dose was defined as the planned number of applications per day (1) * surface (measured) * aimed amount per application (mg/cm2 ). Truly applicated daily dose was evaluated as individual mean amount per dose * individual mean number of applications per day. Adherence was assumed, if truly applicated daily dose is at least 75% of the prescribed daily dose and the individual mean number of applications per day is at least 0.85. Secondary Endpoint Efficacy was measured by improvement of Hand Eczema Severity Index (HECSI) and Investigator's Global Assessment (IGA) after a 4-week treatment period and in addition to Quality of Life in Hand Eczema Questionnaire (QOLHEQ) and Visual Analogue Scale (VAS) to assess pruritus. Number of participants randomized to each group 40, 80 total. Group 1 MPA-C: Methylprednisolone aceponate 0.1% cream and barrier repair emollient (Bepanthen® Sensiderm). Group 2 MPA-FO: Methylprednisolone aceponate 0.1% fatty ointment and barrier repair emollient (Bepanthen® Sensiderm). Adherence to treatment was compared via Fisher's exact test. Of the patients, 48% were adherent according to our definition. There was no significant difference between MPA-C (42.1%) and MPA-FO (54.1%; p = 0.36; group difference-12.0%, 95% CI-34.3%-11.5%). Generalized-linear-model-analysis of adherence to study treatment with factors emollient use, treatment, time and treatment-time interaction showed a parallel between adherence and amount of emollient use (odds ratio 1.74, p = 0.0038; 95% CI-1.22-2.52). Improvement of hand eczema was seen according to clinical scores without remarkable differences between the groups. No dependence of adherence on galenics of topical treatment of chronic hand eczema could be proved. Patients who use more emollient tend to be more adherent to the topical treatment.

Chronic hand eczema (CHE) is a frequent and heterogeneous condition associated with long-lasting symptoms, functional impairment, and high psychosocial and socioeconomic burden. Diagnostic evaluation relies on detailed history taking, physical examination, and patch testing, which remains the gold standard for identifying relevant sensitizations. Disease severity can be assessed with clinician-reported instruments, such as the Hand Eczema Severity Index, and patient-reported outcomes, particularly the Quality of Life in Hand Eczema Questionnaire (QOLHEQ). Management requires a structured, stepwise approach integrating preventive measures with pharmacological interventions. Topical corticosteroids remain the first-line treatment, whereas phototherapy and systemic options, including alitretinoin and immunosuppressants, are indicated in refractory cases. Recently, novel agents such as topical delgocitinib and biologics like dupilumab have expanded the therapeutic armamentarium, particularly for atopic CHE. Preventive strategies, implemented at primary, secondary, and tertiary levels, are crucial for reducing recurrences and improving long-term outcomes. Despite these advances, there is still a lack of standardized diagnostic tools, validated severity measures, and evidence-based treatment algorithms. Future efforts should focus on patient-centered, multidisciplinary care and further research to optimize disease control and quality of life in CHE.

Introduction/Background Chronic Hand Eczema (CHE) is a frequent inflammatory skin disease associated with pain, pruritus, and significant occupational, functional, social, and psychological burden. Delgocitinib is a topical pan-JAK inhibitor which showed a dose-dependent efficacy in adults with CHE in a Phase 2b trial. Objectives The objectives of this analysis were to study (1) the efficacy of twice-daily applications of delgocitinib cream 20 mg/g, as assessed by Investigator's Global Assessment for CHE treatment success (primary outcome), and the secondary outcomes ≥75%/≥90% improvement in Hand Eczema Severity Index and ≥4-point improvement in the Dermatology Life Quality Index, and (2) the safety of twice-daily applications of delgocitinib cream 20 mg/g compared with cream vehicle in the treatment of adults with moderate to severe CHE in a pooled analysis of the DELTA-1 and DELTA-2 trials. Methods In the Phase 3 DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101) trials, adults with moderate to severe CHE were randomized 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was the Investigator's Global Assessment for CHE (IGA-CHE) treatment success at Week 16, defined as IGA-CHE score of 0/1 (clear/almost clear, i.e., no/barely perceptible erythema and no other signs), with a ≥2-step improvement from baseline. Key secondary endpoints included ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) and ≥4-point improvement in the Dermatology Life Quality Index (DLQI). This DELTA-1 and -2 pooled analysis included 639 patients treated with delgocitinib cream and 321 with cream vehicle. Results At Week 16, a significantly greater proportion of delgocitinib-treated patients, versus cream vehicle, achieved IGA-CHE treatment success (24.3% vs. 8.4%; P&amp;lt;0.001), HECSI-75 (49.4% vs. 20.9%; P&amp;lt;0.001), HECSI-90 (30.3% vs. 10.6%; P&amp;lt;0.001), and DLQI ≥4-point improvement (73.3% vs. 47.8%; P&amp;lt;0.001). Most frequent adverse events (occurring in ≥5% of patients) were COVID-19, nasopharyngitis, and headache with similar rates in both treatment groups. Conclusions In the DELTA-1 and -2 pooled analysis, delgocitinib cream twice-daily confirmed its clinical efficacy in patient- and clinician-reported efficacy outcomes versus cream vehicle in adult CHE patients and suggests an innovative treatment option in this often difficult-to-treat patient population.

Management of chronic hand eczema (CHE) remains a challenge; effective topical treatment is limited to corticosteroids. To assess the efficacy and safety of a novel, pan-Janus kinase inhibitor (delgocitinib) in patients with CHE. In this randomized, double-blind, phase IIa study, patients with CHE received delgocitinib ointment 30mg g-1 or vehicle ointment for 8 weeks. The primary end point was the proportion of patients achieving treatment success ['clear'/'almost clear' skin with ≥ 2-point improvement in the Physician's Global Assessment of disease severity (PGA)] at week 8. Secondary end points included Hand Eczema Severity Index (HECSI) score changes and the proportion of patients achieving treatment success on the Patient's Global Assessment of disease severity (PaGA). Ninety-one patients were randomized. More patients receiving delgocitinib (46%) than vehicle (15%) [odds ratio 4·89, 95% confidence interval (CI) 1·49-16·09; P = 0·009] achieved treatment success (PGA). Adjusted mean HECSI score at week 8 was lower with delgocitinib (13·0) than with vehicle (25·8) (adjusted mean difference -12·88,95% CI -21·47 to -4·30; P = 0·003). More patients receiving delgocitinib than vehicle achieved treatment success by PaGA, but this did not reach statistical significance. The incidence of adverse events was similar with delgocitinib and vehicle; none led to discontinuation of delgocitinib. Delgocitinib ointment was efficacious and well tolerated. As a plateau of efficacy was not observed, a longer treatment period may lead to increased efficacy. Further clinical studies are warranted to confirm these findings in patients with CHE. What's already known about this topic? Chronic hand eczema (CHE) has a significant burden. Few randomized controlled studies have evaluated current treatments for CHE; only limited data are available to inform and guide clinical practice decisions. There is currently an unmet need for efficacious and well-tolerated topical treatment options for patients with CHE. What does this study add? Delgocitinib is a novel, pan-Janus kinase (JAK) inhibitor specific for JAK1, JAK2, JAK3 and tyrosine kinase 2. Topical use of delgocitinib ointment resulted in clearance of CHE after 8 weeks of treatment in a significantly greater number of patients than vehicle; delgocitinib was also well tolerated. Results from this proof-of-concept clinical study suggest that topical delgocitinib may provide therapeutic benefit to patients with CHE with inadequate responses to topical corticosteroids.

SummaryBackgroundMeasurement instruments should be validated for use in the population for which they are intended. The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) has been developed to measure impairment of health‐related quality of life in patients with hand eczema.ObjectivesTo assess validity, reproducibility, responsiveness and interpretability of the Dutch version of the QOLHEQ.MethodsThis was a prospective validation study in adult patients with hand eczema. At three time points (T0, baseline; T1, after 1–3 days; T2, after 4–12 weeks), data from the QOLHEQ and multiple reference instruments were collected. Scale structure was assessed using item response theory analysis and structural equation modelling (SEM). Single‐score validity and responsiveness were tested with hypotheses on correlations with reference instruments. Concerning reproducibility, intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were checked. Regarding interpretability, bands for severity of quality‐of‐life impairment were proposed. Also, smallest detectable change (SDC) and minimally important change (MIC) were determined.ResultsAt T0, 300 individuals participated in the study (54% were male, mean age 45 years). Rescoring of the scale structure fitted the Rasch model and the SEM. The ICCagreement was 0·91 (95% confidence interval 0·85–0·94) and the SEMagreement was 5·2 points. Of the a priori formulated hypotheses, 80% (single‐score validity) and 64% (change scores for responsiveness) were confirmed. The SDC was 14·4 points and the MIC was 11·5 points.ConclusionsThe Dutch version of the QOLHEQ has a good structural validity and reproducibility and has a high single‐score validity and moderate responsiveness. An improvement of ≥ 15 points should be regarded as a real, important change within the Dutch population.What's already known about this topic?The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) measures impairment of health‐related quality of life (HRQoL) in patients with hand eczema.The QOLHEQ was validated in Germany and Japan, but the validity and interpretability of the Dutch version are unknown.What does this study add?This study shows that the Dutch QOLHEQ is a valid instrument to measure HRQoL impairment in Dutch patients with hand eczema, demonstrating good reliability and moderate responsiveness.Methods of item response theory are applied to assess and refine the scoring structure.Severity gradings to interpret single and change scores, specifically in Dutch patients, are proposed.What are the clinical implications of this work?The Dutch QOLHEQ can now be used to measure HRQoL impairment in Dutch patients with hand eczema.

Hand eczema is common and can have a large impact on the quality of life of those affected. In this thesis, this impact is studied. Studies into the financial cost of hand eczema are reviewed. Total yearly costs per person vary from €1311 - €9792. Presenteeism (working while having a disease) is often overlooked. It is shown that it is common in more severe hand eczema, often with an occupational cause, and frequently has intrinsic reasons. Studies into the treatment of hand eczema show that azathioprine may be considered in severe hand eczema, although it often has side effects. The novel drug dupilumab probably holds promise for the future treatment of hand eczema. Performing studies and measuring patients is not very useful if unvalidated measurement instruments are used. Therefore, the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) and the Hand Eczema Severity Index (HECSI) are extensively studied in this thesis. For the QOLHEQ national validation of the Dutch version is performed and cross-cultural validation was done for multiple language versions. For the QOLHEQ and HECSI, interpretability is studied to assign meaning to single scores and change scores. Also, it is assessed what the minimally important change is that a patient needs to obtain on these instruments to be regarded truly and importantly changed when compared with an earlier measurement.

The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) is a disease-specific instrument used to assess health-related quality of life (HRQoL) in patients with hand eczema according to the domains of (a) symptoms, (b) emotions, (c) functioning, and (d) treatment/prevention. Today it is not clear what a single score of the QOLHEQ in its German-language version means to a patient. It was the aim of this study to band the QOLHEQ score to an anchor question (AQ) in order to obtain meaningful categories of the QOLHEQ to aid its interpretation. In addition, we assessed the minimal important change (MIC) by using anchor- and distribution-based methods. Overall n = 440 hand eczema patients were included in the study. Mean age was 47.5 years (SD 11.9); 38.4% of the sample were female. With a weighted kappa of 0.62, the total QOLHEQ score showed the best agreement for the following band: QOLHEQ of <17 = no impairment; QOLHEQ of 18-28 = slight impairment; QOLHEQ of 29-41 = moderate impairment; QOLHEQ of 42-79 = severe impairment; and QOLHEQ of >79 = very severe impairment. The MIC for the total score was found to be 16.5 points. This banding represents a standardized means of interpreting the QOLHEQ total score. Our results indicate that a banding study should be performed for each language version of the QOLHEQ.

Chronic hand eczema (CHE) is a burdensome disease, and new well-documented, safe and efficacious treatments are warranted. In a recent CHE phase IIa trial, the pan-Janus kinase (JAK) inhibitor delgocitinib in an ointment formulation was found to be efficacious and well tolerated. This trial assessed the dose response, efficacy and safety of delgocitinib cream in CHE. In this double-blind, phase IIb dose-ranging trial, adults with CHE and a recent history of inadequate response or contraindication to topical corticosteroids were randomized to delgocitinib cream 1, 3, 8, 20 mg g-1 or vehicle treatment twice daily for 16 weeks. The primary endpoint was the Investigator's Global Assessment for CHE (IGA-CHE) treatment success [0 (clear) or 1 (almost clear) with a ≥ two-point improvement from baseline to week 16]. Secondary endpoints were the time to IGA-CHE treatment success and changes in Hand Eczema Severity Index (HECSI); other endpoints were itch and pain numerical rating scale (NRS) scores, and Patient's Global Assessment (PaGA) at week 16. Patients (n = 258) were randomized 1 : 1 : 1 : 1 : 1 to delgocitinib cream 1, 3, 8, 20 mg g-1 or vehicle. A significant dose-response relationship was established for IGA-CHE (P < 0.025). IGA-CHE treatment success at week 16 was achieved in 21.2% (1 mg g-1 ), 7.8% (3 mg g-1 ), 36.5% (8 mg g-1 ), 37.7% (20 mg g-1 ) and 8.0% (vehicle) of patients. Delgocitinib 8 and 20 mg g-1 showed a treatment effect against vehicle (P < 0.001). Similarly, there were improvements in HECSI, itch and pain NRS scores, and PaGA. Delgocitinib cream was well tolerated with the majority of adverse events being mild or moderate and considered unrelated to treatment. The most frequently reported adverse events were nasopharyngitis (17.3-29.4% in delgocitinib groups vs. 40% in vehicle group), eczema (5.8-11.3% in delgocitinib groups vs. 16.0% in vehicle group) and headache (3.8-11.5% in delgocitinib groups vs. 4.0% in vehicle group). In this trial, delgocitinib cream showed a dose-response relationship in terms of efficacy and was well tolerated.