Successful tapering of dupilumab in patients with atopic dermatitis with low disease activity: a large pragmatic daily practice study from the BioDay registry.

BACKGROUND: Limited data are available regarding patient-centred dosing of dupilumab for atopic dermatitis (AD) in daily practice. OBJECTIVES: To evaluate our patient-centred dupilumab dosing regimen in daily practice, to assess prognostic factors for successful tapering and to estimate medication-related cost savings. METHODS: This prospective multicentre study included adult patients with AD, participating in the BioDay registry, treated with dupilumab for ≥ 1.3 years. Interval prolongation was considered in the case of dupilumab standard dose for ≥ 1 year and persistent controlled AD [Eczema Area and Severity Index (EASI) ≤ 7; ≥ 6 months]. Primary endpoints were the mean EASI and Numeric Rating Scale (NRS)-pruritus after the start of tapering. Prognostic factors for successful tapering were analysed with logistic regression and a cost-savings analysis was performed. RESULTS: A total of 595 patients were included, of whom 401 patients [mean EASI 2.5 (SD 2.3); NRS-pruritus of 2.4 (SD 1.9) at the start of tapering] prolonged their dupilumab interval. In 83.3% of these patients tapering was successful; most patients used dupilumab every 3 or 4 weeks (Q3W/Q4W). A significant small increase was observed for EASI (highest mean 3.5) and NRS-pruritus (highest mean 3.2) (P < 0.001); however, scores remained low. Predicting successful tapering showed nonsignificant odds ratios for all incorporated variables. The estimated cost savings was €3 977 033.98 for 401 patients between January 2019 and June 2022. CONCLUSIONS: This study showed successful tapering of dupilumab in 83.3% of patients with AD who attempted tapering, while maintaining controlled disease and with the majority using Q3W/Q4W. Interval prolongation can be beneficial both for the patient and from a socio-economic perspective.

The potency of clobetasol propionate: serum levels of clobetasol propionate and adrenal function during therapy with 0.05% clobetasol propionate in patients with severe atopic dermatitis.

BACKGROUND: Percutaneous absorption of topically applied 0.05% clobetasol propionate (CLO) can be assessed indirectly by measuring cortisol levels. A direct way is to measure systemic levels of topically applied CLO. METHODS: Serum concentrations of CLO were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS), and were related to serum cortisol levels in 25 patients with an exacerbation of atopic dermatitis (AD) before and after the first day of treatment with 0.05% CLO in hospital. The body surface area (BSA) affected by AD was measured. RESULTS: Before the start of 0.05% CLO treatment, normal cortisol levels were measured (0.47 ± 0.18 µmol/l) and CLO concentrations could not be detected. After the first day of treatment, cortisol levels decreased to 0.04 ± 0.05 µmol/l. Serum concentrations of CLO could be detected in all patients (0.112-4.504 ng/ml). Levels did not differ between patients who had received two applications versus one application of 0.05% CLO. There was no correlation between the affected BSA and serum concentrations of CLO. CONCLUSION: Serum levels of CLO can be measured by LC/MS/MS. When prescribing 0.05% CLO, one must bear in mind that, even after an application of 20-30 g, CLO is systemically available and potent enough to induce adrenal gland suppression.

Enteric-coated mycophenolate sodium versus cyclosporin A as long-term treatment in adult patients with severe atopic dermatitis: a randomized controlled trial.

BACKGROUND: Cyclosporin A (CsA) is frequently used in the treatment of severe atopic dermatitis (AD). Enteric-coated mycophenolate sodium (EC-MPS) may be an alternative with equal efficacy and fewer side effects. OBJECTIVE: The aim of this observer-blinded randomized controlled trial was to compare EC-MPS with CsA as long-term treatment in adult patients with severe AD. METHODS: Fifty five patients with AD were treated with CsA (5 mg/kg) in a 6-week run-in period. Thereafter, patients either received CsA (3 mg/kg; n = 26) or EC-MPS (1440 mg; n = 24) during a maintenance phase of 30 weeks and there was a 12-week follow-up period. Disease activity was measured using the objective SCORAD and serum thymus and activation-regulated chemokine (TARC) levels and side effects were registered. RESULTS: During the first 10 weeks the objective SCORAD and serum TARC levels in the EC-MPS study arm were higher in comparison with the CsA study arm. In addition, 7 of the 24 patients treated with EC-MPS required short oral corticosteroid courses. During maintenance phase disease activity was comparable in both study arms. Side effects in both study arms were mild and transient. After study medication withdrawal, disease activity of the patients in the CsA study arm significantly increased compared with the EC-MPS study arm. LIMITATION: The nonblinding of patients and prescriber of rescue medication are limitations. CONCLUSIONS: This study shows that EC-MPS is as effective as CsA as maintenance therapy in patients with AD. However, clinical improvement with EC-MPS is delayed in comparison with CsA. Clinical remission after stopping EC-MPS lasts longer compared with CsA.

Topical corticosteroids in atopic dermatitis and the risk of glaucoma and cataracts.

INTRODUCTION: There is concern about the development of glaucoma and cataracts associated with topical corticosteroid use in patients with atopic dermatitis (AD). OBJECTIVE: We evaluated glaucoma and cataract development in patients with AD to determine whether they are associated with the cumulative dose of topical steroids and the use of topical corticosteroids on the eyelids and periorbital region. METHODS: In all, 88 patients with AD were recruited from the University Medical Centre Utrecht. Patients were interviewed and completed a questionnaire assessing different factors such as AD involvement of eyelids and periorbital skin. The use of corticosteroids in previous years was obtained from pharmacy records. A complete ophthalmologic examination was performed for the presence of glaucoma and cataracts. RESULTS: Of the 88 patients (41 men and 47 women), with an average age of 37.2 ± 14.3 years (mean ± SD), one patient had transient ocular hypertension and one patient had optic disc cupping without any glaucomatous defects in his visual field. Seven patients were given the diagnosis of cataracts (one AD-related, two corticosteroid-induced, and 4 age-related). Both patients with corticosteroid-induced cataracts had also used systemic corticosteroids. In all, 37 of the 88 patients had used topical corticosteroids (class III and IV) on the eyelids and periorbital region, with an average frequency of 3.9 days per week and 6.4 months per year for 4.8 years. LIMITATIONS: Small sample size, objectiveness of patient recall about the use of topical corticosteroids on the eyelids/periorbital region, overestimation of topical corticosteroid use from pharmacy records, and lack of information on lifetime corticosteroid use were limitations. CONCLUSIONS: In this retrospective study glaucoma was not seen; two patients with AD had corticosteroid-induced cataracts, which were probably caused by the use of systemic corticosteroids. The application of topical corticosteroids to the eyelids and periorbital region, even over longer periods of time, was not related to the development of glaucoma or cataracts in this study population.

Bone mineral density in children with moderate to severe atopic dermatitis.

BACKGROUND: Low bone mineral density (BMD) has been reported in 30.4% of adult patients with atopic dermatitis (AD). OBJECTIVE: The aim of this study was to determine the prevalence of low BMD in children with moderate to severe AD and to investigate the relation between BMD and corticosteroid and cyclosporine therapy. METHODS: Lumbar spine BMD was measured by dual-energy X-ray absorptiometry in 60 children (age 5-16 years) with moderate to severe AD. BMD (in g/cm(2)) was expressed in Z-scores, the number of SD above or below the mean value of an age- and sex-matched reference population. In children, low BMD was defined as a Z-score less than -2. Information on lifestyle parameters and bone fractures were collected by use of a standardized questionnaire. The cumulative dose of corticosteroids and cyclosporine therapy was calculated for the previous 5-year period. RESULTS: Three patients (5%) had low BMD; one patient (1.7%) had osteoporosis. The observed prevalence of low BMD in this study (6.7%; 95% confidence interval 1.8%-16.2%) does not differ from the expected prevalence of low BMD in the general population (P = .06). Overall, use of topical corticosteroids in the previous 5 years was not associated with a decrease in BMD (Z-score). When children received additional systemic treatment (oral corticosteroids and/or cyclosporine) in the previous 5 years, BMD decreased, although the decrease was not statistically significant. Correction for lifestyle parameters did not change these associations. LIMITATIONS: The number of patients studied was limited. The cumulative dose of corticosteroids and cyclosporine therapy was only registered for the previous 5 years, and relatively low amounts of topical corticosteroids were used. The definition of low BMD differs between adults (Z-score < -1) and children (Z-score < -2). Because there is no Dutch BMD reference population for children, normative BMD references were obtained from a different population (US children). CONCLUSIONS: Low BMD did not occur more frequently in this population of children with moderate to severe AD compared with the general population. Use of topical corticosteroids in the previous 5 years was not associated with a decrease in BMD.

The Self-administered Eczema Area and Severity Index in children with moderate to severe atopic dermatitis: better estimation of AD body surface area than severity.

The Self-Administered Eczema Area and Severity Index (SA-EASI) is one of the few patient based atopic dermatitis (AD) disease activity scores and was found to be highly correlated with the EASI. Correlation with other frequently used scoring methods has not been investigated. The aim of this study was to evaluate the relation of the SA-EASI with two physician-based disease activity scores (objective SCORAD and SASSAD score) and with a serum marker for AD (Thymus and Activation-Regulated Cytokine [TARC]) in children with AD. Sixty children with moderate to severe AD were included. The SA-EASI was completed by caregivers, and the objective SCORAD and SASSAD scores were measured successively on the same day by a trained investigator. Blood for serum TARC measurement was drawn. The correlation between the SA-EASI and the objective SCORAD was high (ρ = 0.61, p = <0.001), mainly based on high correlation between the body surface area (BSA) measurements of both scores (ρ = 0.50, p = <0.001). The correlation with the SASSAD score (only severity measurement) was 0.43 (p = <0.001). The correlation with serum TARC levels was 0.46; p = <0.001, mainly based on the BSA score of the SA-EASI (ρ = 0.42, p = <0.001). Parents may have more difficulty in scoring severity of AD than scoring BSA involved. Educating parents in severity scoring of AD may improve agreement of the SA-EASI and the objective SCORAD, TARC, and SASSAD score. Additional use of the SA-EASI in routine clinical practice or in trials may then facilitate more frequent but still accurate assessment of AD.