Effectiveness of dupilumab treatment in 95 patients with atopic dermatitis: daily practice data.

BACKGROUND: Dupilumab is the first biologic registered for the treatment of moderate-to-severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants. OBJECTIVES: To evaluate dupilumab treatment in daily practice in patients with AD. METHODS: In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician-reported outcome measures and patient-reported outcome measures (PROMs) after ≥ 12 weeks of follow-up were analysed. We used a linear mixed-effects model to determine changes in scores during follow-up. RESULTS: Ninety-five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during dupilumab treatment in 43 patients. From baseline to 16 weeks of treatment, the estimated mean Eczema Area and Severity Index score (0-72) decreased from 18·6 [95% confidence interval (CI) 16·0-21·4)] to 7·3 (95% CI 5·4-10·0), and the estimated mean PROMs showed a decrease of 41-66%. Investigator's Global Assessment 0 or 1 (clear/almost clear) was reached in 38% of the patients. Five patients discontinued dupilumab treatment due to side-effects or ineffectiveness. Eye symptoms and orofacial (nonocular) herpes simplex virus (HSV) reactivation were reported in 62% and 8% of the patients, respectively. CONCLUSIONS: Dupilumab treatment in daily practice shows a clinically relevant improvement of physician-reported outcome measures and PROMs, which is in line with efficacy data from clinical trials. Besides frequently reported eye symptoms and orofacial (nonocular) HSV reactivation, there were no apparent safety concerns. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for atopic dermatitis in several clinical trials. However, it is known that there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice. What does this study add? This study presents the first experience with dupilumab treatment in 95 patients with atopic dermatitis in daily practice in two Dutch university hospitals. Less stringent inclusion and exclusion criteria and follow-up schedules, in contrast to those used in clinical trials, might better represent daily practice. Dupilumab treatment shows a clinically relevant improvement of physician- and patient-reported outcome measures; besides patient-reported eye symptoms (in 59 of 95 patients; 62%) and an apparent increase in orofacial (nonocular) herpes simplex virus reactivation (eight of 95 patients; 8%), there were no other safety concerns during follow-up up to 16 weeks of dupilumab treatment.

Clinical and histopathological characterization of paradoxical head and neck erythema in patients with atopic dermatitis treated with dupilumab: a case series.

Dupilumab is the first biologic registered for the treatment of atopic dermatitis (AD). We report on seven patients with AD presenting with a paradoxical head and neck erythema that appeared 10-39 weeks after the start of dupilumab treatment. The patients presented with a relatively sharply demarcated, patchy erythema in the head and neck area that showed no or less scaling compared with their usual eczema. Only one patient experienced symptoms of itch and burning, although this was notably different from his pre-existent facial AD. Except for a notable 'red face', eczema on other body parts had greatly improved in six of the seven patients, with a mean numerical rating scale for treatment satisfaction of 9 out of 10 at the time of biopsy. Treatment of the erythema with topical and systemic drugs was unsuccessful. Despite the presence of this erythema, none of our patients discontinued dupilumab treatment. Lesional skin biopsies showed an increased number of ectatic capillaries, and a perivascular lymphohistiocytic infiltration in all patients. In addition, epidermal hyperplasia with elongation of the rete ridges was observed in four patients, resembling a psoriasiform dermatitis. Additional immunohistochemical stainings revealed increased numbers of plasma cells, histiocytes and T lymphocytes. Interestingly, spongiosis was largely absent in all biopsies. We report on patients with AD treated with dupilumab developing a paradoxical erythema in a head and neck distribution. Both clinically and histopathologically we found a heterogeneous response, which was most suggestive of a drug-induced skin reaction.

[Hypersensitivity reactions to excipients in patches]. / Overgevoeligheid voor hulpstoffen in pleisters.

The most common side effects of transdermal patches are mechanical reactions caused by applying or removing the transdermal patch, or by excessive perspiration under the patch. Allergic contact dermatitis (type IV allergic reaction) is the most commonly occurring hypersensitivity reaction and can be caused by the active substance or by excipients. Type I allergic reactions such as urticaria, bronchospasm and angioedema are rare and usually caused by the active substance in the patch. Allergy testing to determine the allergen is indicated following a type I allergic reaction, or after a type IV allergic reaction that requires an alternative for the patch. It is important to document hypersensitivity reactions in the electronic patient records in order to prevent a hypersensitivity reaction in the future.

A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: quality-of-life outcomes of a randomized controlled trial of supervised treatment of psoriasis in a day-care setting.

BACKGROUND: Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease. OBJECTIVES: To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). RESULTS: At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36. CONCLUSIONS: The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.

A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day-care setting.

BACKGROUND: Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol. OBJECTIVES: To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. RESULTS: This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0% in the calcipotriol group vs. 63.6% in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups (P = 0.39). At the end of treatment, 15% of the patients treated with calcipotriol ointment and 25% of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant (P = 0.001). CONCLUSIONS: The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.