Klaziena Politiek

Drug survival for ciclosporin A in a long-term daily practice cohort of adult patients with atopic dermatitis

Long‐term data of ciclosporin A (CsA) treatment in daily practice in patients with severe atopic dermatitis (AD) are lacking.

Drug survival for methotrexate in a daily practice cohort of adult patients with severe atopic dermatitis

DEAR EDITOR, Methotrexate is prescribed off-label for atopic dermatitis. Some clinical studies of methotrexate treatment in atopic dermatitis have demonstrated effectiveness, although the number of patients was small and the treatment and follow-up periods were relatively short. Therefore, we conducted an analysis of drug survival for methotrexate in a long-term daily practice cohort of patients with severe atopic dermatitis. This retrospective study was performed at the dermatology departments of the University Medical Center Groningen and the University Medical Center Utrecht. In both centres all patients are registered according to the 10th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). The patients for the study were identified using the morbidity atopic dermatitis (XII-L20) and laboratory monitoring in the same period. Laboratory monitoring is mandatory during treatment with systemic therapy and liver function parameters were used to identify subjects treated with methotrexate. Patients aged ≥ 18 years with atopic dermatitis according to the U.K. Working Party’s Diagnostic Criteria, who were treated between 1997 until data lock in February 2015, were included. Data were retrieved from medical charts that were prespecified for atopic dermatitis. Treatment with methotrexate was initiated with a dosage of 5–10 mg per week and gradually increased based on clinical signs with a maximum of 5 mg per visit (maximum total dosage 25 mg per week), according to a standard follow-up protocol in both centres. Some patients received concomitant prednisolone (10–30 mg per day) during the start-up phase, for crisis intervention or a low maintenance dose (5 mg per day) during their complete methotrexate treatment. A retrospective Physician’s Global Assessment (PGA) score was used to measure an overall treatment response at the moment of discontinuation or data lock. The improvement of lesions relative to the baseline (before starting methotrexate) was categorized into the following three groups: (i) PGA1, good effect of treatment; (ii) PGA2, moderate effect and (iii) PGA3, failure of treatment (no improvement or worse). Treatment episodes shorter than 8 weeks were not given a PGA score. Only the first methotrexate treatment episodes were analysed. Treatment interruptions up to 14 days were considered as a continuous treatment episode. Drug survival rates of methotrexate were analysed using Kaplan–Meier survival curves. Three events for drug survival were analysed separately: (i) discontinuation overall; (ii) discontinuation due to side-effects and (iii) discontinuation due to ineffectiveness. Patients were censored when lost to follow-up, still active at the moment of data lock or discontinued due to an event other than the event of interest. Possible determinants of drug survival for the events of interest (side-effects or ineffectiveness) were analysed by a univariate Cox regression model and assumptions of proportional hazards were checked and met. Determinants with a P-value < 0 2 were entered in a multivariate Cox regression model. A full model was created by backward selection and P-values < 0 05 were considered statistically significant. Data analyses were performed using SPSS Statistics 22.0 (IBM, Armonk, NY, U.S.A.). A total of 89 patients were included. The baseline characteristics are displayed in Table 1. The median treatment duration was 223 days (range 11–1387) with a total of 69 3 patientyears. At the moment of data lock 35 patients (39%) still used methotrexate; two of these patients used concomitant prednisolone. Overall, 49% of the patients showed a good response to methotrexate treatment (PGA1) at the moment of discontinuation or data lock (Table 1). Of 20 patients who used methotrexate for more than 1 year, a total of 16 patients (80%) had a PGA1 score. Side-effects and ineffectiveness were the main reasons for discontinuation of methotrexate in 25% and 15% of the patients, respectively. In cases of treatment failure, patients discontinued treatment due to side-effects or ineffectiveness in the first year only and not later in the treatment. The overall drug survival showed that 73%, 41% and 34% of the patients still used methotrexate after 6 months, 1 year and 2 years, respectively (Fig. 1). The median drug survival was 9 8 months [95% confidence interval (CI) 7 7–11 9]. After 6 months, 1 year and 2 years, the treatment was discontinued in 10%, 24% and 24%, respectively, of the patients owing to ineffectiveness. Side-effects were a reason for discontinuation in 17%, 33% and 33% of the patients after 6 months, 1 year and 2 years, respectively. Univariate Cox regression analysis demonstrated that a higher maintenance dose (dose in intervals of 5 mg kg ) was associated with a decreased drug survival related to ineffectiveness [hazard ratio (HR) 2 84, 95% CI 1 28–6 31; P = 0 01] and an increased drug survival related to side-effects (HR 0 42, 95% CI 0 22– 0 82; P = 0 01). Male sex, older age (age in 5-year intervals),

Drug survival for azathioprine and enteric-coated mycophenolate sodium in a long-term daily practice cohort of adult patients with atopic dermatitis

Results from clinical studies indicate that azathioprine and enteric-coated mycophenolate sodium (EC-MPS) are safe and potent drugs in the treatment of atopic dermatitis (AD).(1-5) However, published data from large groups of non-selected patients is non-existent to date which hampers generalization to daily practice. In addition, head-to-head trials in which azathioprine and EC-MPS are compared, have never been performed. The primary objective was to perform an analysis of drug survival for azathioprine and EC-MPS in a long-term daily practice cohort of patients with AD. The secondary objective was to identify determinants of drug survival. This article is protected by copyright. All rights reserved.

Systematic review of cost-of-illness studies in hand eczema

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 €1712 to €9792 (direct cost per patient, €521 to €3829; 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.

Drug survival of cyclosporine in the treatment of hand eczema: a multicentre, daily use study

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.

Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the University Medical Center Utrecht and Groningen, the Netherlands, were analysed. NMSC after oral immunosuppressive treatment was reported in 18 patients (3.2%). The standardized incidence ratio for developing SCC was 13.1 (95% confidence interval (95% CI) 6.5-19.7). Patients developing NMSC were older at the start of therapy (p<0.001) and data lock (p<0.001) compared with patients without NMSC. No significant differences were found in sex, cumulative days of oral immunosuppressive drugs and follow-up between these groups (p=0.42, p=0.88, and p=0.34, respectively). In interpreting these results it is important to include other factors, such as lack of association between treatment duration and tumour development and the long interval between treatment discontinuation and tumour development in some patients.

Drug survival of methotrexate treatment in hand eczema patients: results from a retrospective daily practice study

for the negative result of CEA in the Bowenoid lesions (Fig. 2b). Therefore, to confirm the cell lineage of Bowenoid cells, Ber-EP4 and CK5/6 staining were added. EMPD has been reported to stain positive with Ber-EP4, whereas Bowen’s disease stains negative. CK5/6 are positive in Bowen’s disease, but negative in EMPD. The Bowenoid cells in our case demonstrated the characteristic immunohistochemical features of Paget cells (Fig. 2c, d). These results indicate that the Bowenoid cells in our case were not derived from keratinocytes. In summary, our detailed pathological examination, in addition to the literature review, has clarified the immunohistochemical profiles of EMPD with Bowenoid features. We propose that Ber-EP4 and CK5/6 staining can improve the diagnostic accuracy when the clinician suspects atypical cases of Bowenoid EMPD.

Azathioprine treatment and drug survival in patients with chronic hand eczema - results from daily practice

We retrospectively reviewed patient records between January 2000 and 16 December 2015 (data lock). Patients were identified according to the International Classification of Disease (10th edition) diagnoses L20, L23-25, and L30. We included adult patients with severe chronic hand eczema who were treated with azathioprine. Patients with concomitant mild atopic dermatitis on other body areas were also included.

Occupational allergic contact dermatitis caused by 1‐propanol in a hand disinfectant

Hand eczema is a common occupational skin disease in healthcare workers. This is often the result of repeated contact with irritants, such as water; however, contact allergy can also be the underlying cause. In this report, we describe a patient with occupational hand eczema, caused by contact allergy to 1-propanol (CAS no. 71-23-8; synonyms n-propanol and n-propyl alcohol), which was present in the hand disinfectant Sterillium®.

Allergic contact dermatitis in two employees of an ethylene amine-producing factory

Ethylenediamine [EDA, C2H4(NH2)2, CAS no. 107-15-3] is an aliphatic amine with a broad range of applications in rubber, dyes, insecticides, and synthetic waxes. Historically, the most common reason for allergic contact dermatitis caused by EDA was its use as a stabilizer in topical medicaments (e.g. Mycolog® cream) (1, 2). This application of EDA has been discontinued. In 1995, EDA was removed from the European baseline series because of the low incidence of EDA sensitization (3). However, it is still present in the bronchodilator aminophylline, and is often found in occupational settings (4). In this article, we present two process operators with allergic contact dermatitis caused by EDA working in the same company producing ethylene amines.