Abstract and Introduction
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.
Atopic dermatitis (AD) is a complex and heterogeneous chronic inflammatory skin disease. AD is characterized by severe itch and recurrent eczematous lesions. Up to 20% of the worldwide paediatric population and approximately 2–10% of all adults have AD.[1,2] AD can have a profound negative effect on quality of life as it is the skin disease with the highest nonfatal health burden.
In addition to being advised to avoid triggers and use moisturizers, patients with AD are mostly treated with topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). Around 15% of patients with AD are considered to have moderate-to-severe disease requiring phototherapy or systemic immunosuppressive therapy.[3,4] The use of systemic glucocorticosteroids, phototherapy and conventional systemic immunosuppressive agents, including ciclosporin A, azathioprine, mycophenolic acid, mycophenolate mofetil and methotrexate, can be effective and is well tolerated in many patients but may have limitations such as side-effects and an unfavourable risk–benefit ratio.[5–7] In addition, most of these treatments are used off-label and there are limited long-term treatment data available.[5,8–10]
Dupilumab, the first biologic for the treatment of moderate-to-severe AD, is a fully human IgG4 monoclonal antibody that targets the interleukin (IL)-4 receptor α chain, inhibiting the effects of cytokines IL-4 and IL-13. These cytokines are thought to play a central role in the pathogenesis of AD. Dupilumab has been approved recently, after it was shown to be a successful treatment for AD in several phase III clinical trials.[11–13] These trials showed improvement of disease severity, itch, sleep disturbance, anxiety, depression and quality of life with dupilumab as monotherapy or in combination with TCSs. The most frequently observed side-effects were conjunctivitis, herpes infections and injection-site reactions.[3,11]
However, there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice (i.e. efficacy vs. effectiveness). This is partly explained by strict inclusion and exclusion criteria, treatment adherence and prohibited medication and procedures in clinical trials, which may limit the ability to answer questions related to daily practice. Observational studies in a real-world setting are therefore essential to document the benefits and harms of a therapy in a wider patient population. Here, we present and evaluate daily practice data for dupilumab treatment combined with the use of systemic immunosuppressants in patients with AD.
The British Journal of Dermatology. 2020;182(2):418-426. © 2020 Blackwell Publishing