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Background Although atopic dermatitis (AD) is a very common skin disease, data on the percentage of patients with really difficult-to-treat AD are scarce. From socio-economic perspective, it is important to have more insight into these numbers, as new very effective, but expensive, treatment options will be available in the near future for difficult-to-treat AD. Estimating the number of patients with AD using oral immunosuppressive drugs can give an impression of the percentage of difficult-to-treat patients in the total AD population. Objective To give an overview of the use of oral immunosuppressive drugs in patients with AD in the Netherlands. Methods Prescription data of oral immunosuppressive drugs in the Netherlands were extracted from a pharmaceutical database (NControl) containing data of 557 million prescriptions and 7.2 million patients. An algorithm, based on the WHO Anatomical Therapeutic Chemical (ATC) codes, was used to identify patients with AD. The prescription of oral immunosuppressive drugs in patients with AD between 1 January 2012 and 1 January 2017 was evaluated. Results Based on the algorithm, 65 943 patients with AD were selected. 943 patients with AD (1.4%) used cyclosporine A, methotrexate, azathioprine or mycophenolic acid. Methotrexate was most commonly used, followed by azathioprine and cyclosporine A. A switch in medication was rarely seen. In the evaluation period, a decrease in the prescription of cyclosporine A was seen, together with an increase in the prescription of methotrexate. In 31% of the patients who stopped treatment, the discontinuation took place within the first months of treatment. Conclusion In this study population, 1.4% of the patients with AD used oral immunosuppressive drugs for their eczema in a 5-year period. Methotrexate was the most commonly used systemic drug in the Netherlands for the treatment of AD. [ABSTRACT FROM AUTHOR]

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]

Summary: Background: Guidelines discourage the use of systemic corticosteroids for atopic dermatitis (AD), but their use remains widespread. Objectives: To reach consensus among an international group of AD experts on the use of systemic corticosteroids for AD. Methods: A survey consisting of statements accompanied by visual analogue scales ranging from ‘strongly disagree’ to ‘neutral’ to ‘strongly agree’ was distributed to the International Eczema Council (IEC). Consensus was reached in agreement on a statement if < 30% of respondents marked to the left of ‘neutral’ towards ‘strongly disagree’. Results: Sixty of 77 (78%) IEC members participated. Consensus was reached on 12 statements, including that systemic corticosteroids should generally be avoided but can be used rarely for severe AD under certain circumstances, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event or in the most severe cases. If used, treatment should be limited to the short term. Most respondents agreed that systemic corticosteroids should never be used in children, but consensus was not reached on that statement. The conclusions of our expert group are limited by a dearth of high‐quality published evidence. If more stringent consensus criteria were applied (e.g. requiring < 20% of respondents marking towards ‘strongly disagree’), consensus would have been reached on fewer statements. Conclusions: Based on expert opinion from the IEC, routine use of systemic corticosteroids for AD is generally discouraged and should be reserved for special circumstances. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93–80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage. [ABSTRACT FROM AUTHOR]

Background Severe atopic dermatitis (AD) is often treated successfully with oral immunosuppressive drugs such as ciclosporin (CsA) or oral corticosteroids. However, some patients develop adverse effects or are unresponsive to these first-choice oral immunosuppressive drugs. Objectives To evaluate whether enteric-coated mycophenolate sodium (EC-MPS) is an effective treatment in patients with severe, recalcitrant AD. Methods Ten patients with severe, recalcitrant AD were treated with EC-MPS 720 mg twice daily for 6 months. All patients had to discontinue other oral immunosuppressive drugs due to adverse effects ( n = 8) or nonresponsiveness ( n = 2). Disease activity was monitored using the Severity Scoring of Atopic Dermatitis (modified SCORAD) index and the Leicester Sign Score (LSS). Additionally, the level of serum thymus and activation-regulated cytokine (TARC) was measured. During treatment, safety laboratory examination was performed. Total serum immunoglobulin E (IgE) was followed during treatment. Use of topical corticosteroids was recorded before and during treatment. Results Compared with baseline, the mean scores for disease activity significantly decreased during treatment with EC-MPS [modified SCORAD ( P = 0·04), LSS severity ( P = 0·01), LSS extent ( P = 0·01)]. In addition, serum TARC levels and total serum IgE levels significantly decreased after treatment compared with before ( P = 0·03; P = 0·05). Disease activity decreased after approximately 2 months of treatment and stabilized during the 6-month treatment period. No differences in the amount of topical corticosteroids used in the 6 months prior to treatment compared with the 6-month treatment period were found ( P = 0·4). None of the patients discontinued use of EC-MPS and only mild adverse effects were seen. Conclusions In this study EC-MPS at a dose of 720 mg twice daily for 6 months has proven to be an effective and well-tolerated treatment for patients with severe, recalcitrant AD. [ABSTRACT FROM AUTHOR]

Background: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis (AD) patients. Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. The current study investigates the effect of mepolizumab therapy on the APT in the same patients. Methods: Mepolizumab treatment was given at days 0 and 7 in a double-blind placebo-controlled design. The APT was applied at days –2, 0, 14 and 28. Clinical evaluation of each APT was conducted 48 h after application at days 0, 2, 16 and 30. Skin biopsies were taken at days 0, 2 and 16 for eosinophil counts. Results: The mepolizumab-treated group showed no significant reduction in macroscopic outcome of the APT. Tissue eosinophils were reduced in the mepolizumab-treated group at day 16 compared with placebo; however, this was not significant. Conclusion: Mepolizumab therapy cannot prevent the eczematous reaction induced by the APT. Furthermore, the influx of tissue eosinophil numbers in the APT is not significantly inhibited after mepolizumab treatment compared with placebo, despite a significant reduction in peripheral blood eosinophils. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]