Search

Background: Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment. Objective: To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema. Methods: Azathioprine metabolite levels were measured in eczema patients during maintenance treatment (Part I) and dose escalation (Part II). Clinical effectiveness, hepatotoxicity, and bone marrow suppression were analyzed and TPMT genotype was assessed. Results: A wide variation in metabolite levels in all dose groups was observed. In Part I (32 patients), there were no significant differences in 6-TGN levels between clinical responders and non-responders (p = .806). No hepatoxicity or myelotoxicity was observed. In Part II, all 6-TGN and 6-MMP levels increased during dose escalation. Hypermethylation was observed in 2/8 patients. Conclusion: For individual eczema patients treated with azathioprine, routinely measuring 6-TGN and 6-MMP can be helpful in optimizing azathioprine dose, improving clinical effectiveness, and preventing side effects. [ABSTRACT FROM AUTHOR]

Dupilumab treatment improves signs, symptoms, and quality of life in patients with moderate-to-severe atopic dermatitis. This study evaluated the impact of dupilumab treatment on absenteeism, presenteeism, and related costs in a large multi-centre cohort of adult patients with difficult-to-treat atopic dermatitis in daily practice. Patients treated with dupilumab participating in the Dutch BioDay Registry reporting employment were included. Absenteeism, presenteeism, and related costs at baseline and during follow-up were calculated using the Work Productivity and Activity Impairment questionnaire. A total of 218 adult patients with moderate-to-severe atopic dermatitis were included. Total work impairment reduced significantly from baseline (35.5%) to week 52 (11.5%), p < 0.001. Median weekly productivity losses reduced significantly from baseline (€379.8 (140.7-780.8)) to week 52 (€0.0 (0.0-211.0), p < 0.001). In this study, dupilumab treatment demonstrated a significant improvement in work productivity and reduction in associated costs in a large cohort of patients with difficult-to-treat atopic dermatitis in daily practice.

Background: Real-life data on long-term effectiveness and safety of dupilumab in atopic dermatitis patients are limited., Objective: To study 52-week effectiveness and safety of dupilumab in a prospective multicenter cohort of adult patients with treatment-refractory atopic dermatitis., Methods: Patients treated with dupilumab and participating in the Dutch BioDay registry were included. Clinical effectiveness and safety were evaluated., Results: Two hundred ten atopic dermatitis patients were included. Mean percentage change in Eczema Area and Severity Index score after 16 weeks was -70.0% (standard deviation 33.2%) and further decreased to -76.6% (standard deviation 30.6%) by week 52. A greater than or equal to 75% improvement in the score was achieved by 59.9% of individuals by week 16 and by 70.3% by week 52. The most reported adverse effect was conjunctivitis (34%). Limited patients (17; 8.1%) discontinued dupilumab treatment., Limitations: Because of the lack of a control group and observational design, factors of bias may have been induced., Conclusion: Treatment with dupilumab resulted in a rapid improvement in clinical outcome measures, and effectiveness further improved during the 52-week follow-up period., (Copyright © 2020. Published by Elsevier Inc.)

Background: Atopic dermatitis (AD) is a highly heterogeneous disease, both clinically and biologically, whereas patients are still being treated according to a "one-size-fits-all" approach. Stratification of patients into biomarker-based endotypes is important for future development of personalized therapies., Objective: Our aim was to confirm previously defined serum biomarker-based patient clusters in a new cohort of patients with AD., Methods: A panel of 143 biomarkers was measured by using Luminex technology in serum samples from 146 patients with severe AD (median Eczema Area and Severity Index = 28.3; interquartile range = 25.2-35.3). Principal components analysis followed by unsupervised k-means cluster analysis of the biomarker data was used to identify patient clusters. A prediction model was built on the basis of a previous cohort to predict the 1 of the 4 previously identified clusters to which the patients of our new cohort would belong., Results: Cluster analysis identified 4 serum biomarker-based clusters, 3 of which (clusters B, C, and D) were comparable to the previously identified clusters. Cluster A (33.6%) could be distinguished from the other clusters as being a "skin-homing chemokines/IL-1R1-dominant" cluster, whereas cluster B (18.5%) was a "T H 1/T H 2/T H 17-dominant" cluster, cluster C (18.5%) was a "T H 2/T H 22/PARC-dominant" cluster, and cluster D (29.5%) was a "T H 2/eosinophil-inferior" cluster. Additionally, by using a prediction model based on our previous cohort we accurately assigned the new cohort to the 4 previously identified clusters by including only 10 selected serum biomarkers., Conclusion: We confirmed that AD is heterogeneous at the immunopathologic level and identified 4 distinct biomarker-based clusters, 3 of which were comparable with previously identified clusters. Cluster membership could be predicted with a model including 10 serum biomarkers., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce., Objective: To study the effect of 16-week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate-severe AD in daily practice., Methods: Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen-week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI-50 (Eczema Area and Severity Index) or EASI-75, as well as patient-reported outcomes measures (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty-one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks)., Results: In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult-to-treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI-50 and EASI-75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity-related serum biomarkers (TARC, PARC, periostin, and IL-22), eotaxin-1, and eotaxin-3 significantly decreased., Conclusion: Treatment with dupilumab significantly improved disease severity and decreased severity-related serum biomarkers in patients with very difficult-to-treat AD in a daily practice setting., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Purpose of Review: The IL-4/13 antagonist dupilumab was approved in 2017 as the first biologic for atopic dermatitis. Here, we comprehensively review compelling new data regarding dupilumab published following the approval., Recent Findings: Daily clinical practice reports of dupilumab in atopic dermatitis are favorable and in line with the registration trials. Dupilumab does not appear to negatively affect pharmacokinetics of CYP450-metabolized drugs nor vaccination responses. Type 2 inflammation biomarkers in skin and serum are reduced following dupilumab treatment. Dupilumab increases the risk for conjunctivitis, especially with higher baseline atopic dermatitis severity and a history of conjunctivitis, but the underlying mechanisms are unknown. Favorable effects of dupilumab have been reported in treatment-recalcitrant hand eczema and prurigo nodularis cases; for allergic contact dermatitis and alopecia areata, there are conflicting responses to dupilumab, possible stemming from pathophysiological heterogeneity., Summary: Daily practice data support the continued use of dupilumab for atopic dermatitis. The only safety signal is an increased risk for conjunctivitis; mechanistic studies into dupilumab-associated conjunctivitis should lead to risk mitigation strategies. Prospective, controlled evaluations are needed for dupilumab in hand eczema and prurigo nodularis. A precision medicine-driven drug-development approach is essential to assess dupilumab for diseases with heterogeneous pathophysiologies, such as alopecia areata and allergic contact dermatitis.

Given the introduction of new therapies targeting specific immune pathways for atopic dermatitis (AD), information on the economic burden of AD patients is needed. Direct costs (medication use and healthcare resource utilization) and costs of productivity loss were studied in 90 adult patients with AD indicated for systemic treatment. Costs were calculated for patients with controlled (Investigator Global Assessment (IGA) 0-2) and uncontrolled (IGA 3-5) disease at inclusion. Mean (95% confidence interval (95% CI)) total direct costs were €5,191 (€4,382-6,019) per patient per year (PPY), €4,401 (€3,695-5,215) for patients with controlled AD vs. €6,993 (€5,552-8,406), mean difference €2,593 (€820-4,282) (p=0.014) for patients with uncontrolled AD. Costs of productivity loss were €10,040 (€6,260-14,012) PPY for the total group, €6,886 (€4,188-10,129) PPY for patients with controlled AD vs. €13,702 (€6,124-22,996) for patients with uncontrolled AD, mean difference €6,816 (-€1,638-16,677; p=0.148). Total costs (direct costs+costs of productivity loss) were €15,231 (€11,487-19,455) PPY for the total group, €11,287 (€7,974-15,436) for patients with controlled AD vs. €20,695 (€14,068-34,564), mean difference €9,408 (-€119-19,964) (p=0.077) for patients with uncontrolled AD. Patients with AD using systemic immunosuppressive treatment incur considerable direct costs and costs of productivity loss.