Acta Dermato-Venereologica 99-4CompleteContent | Page 8

375 CLINICAL REPORT Eye Complications During Dupilumab Treatment for Severe Atopic Dermatitis Lina U. IVERT 1 , Carl-Fredrik WAHLGREN 1 , Lena IVERT 2 , Maria LUNDQVIST 1 and Maria BRADLEY 1 Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, and 2 Department of Clinical Neuroscience, Division of Ophthalmology and Vision, Karolinska Institutet, Stockholm, Sweden 1 Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated significant clinical effect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated con- junctivitis where reported in a minority of patients. The present case series describe 10 patients treated with dupilumab where eye complications were very common. We have described patient characteristics, including FLG mutations, atopic history and clinical ef- fect of dupilumab. Nine of 10 developed eye-complica- tions, most commonly conjunctivitis (in 7/10). Other adverse events were herpes simplex virus uveitis and varicella-zoster virus meningitis. Although our case series is small, we conclude that dupilumab is an ef- fective treatment option in severe atopic dermatitis, but that the risk of adverse events from the eyes and recurrence of herpes virus infections should be kept in mind. Close collaboration with an ophthalmologist is recommended, especially among patients with se- vere, long-lasting atopic dermatitis and/or previous eye disease. Key words: atopic dermatitis; dupilumab; efficacy; ocular ad- verse events; safety. Accepted Jan 16, 2019; E-published Jan 17, 2019 Acta Derm Venereol 2019; 99: 375–378. Corr: Lina U. Ivert, Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, SE-171 76 Stockholm. E-mail: [email protected] A topic dermatitis (AD) is a common chronic in- flammatory skin disease characterized by a T-cell (Th2)-mediated immune response and epidermal dys- function (1). The prevalence of AD in industrialized countries has increased over recent decades, and is currently estimated to be in the range 15–30% in child- ren and 2–10% in adults (2). Topical therapies, such as glucocorticoids, calcineurin inhibitors and moisturizers, and phototherapy have limited efficacy in moderate to severe AD. Severe cases of AD are treated with systemic drugs, such as cyclosporine, azathioprine, methotrexate (MTX) and mycophenolate mofetil. All of these drugs are used off-label, with the exception of cyclosporine, which is approved for short-term treatment of severe AD (1). AD can be a challenge to treat, and off-label systemic treatments may be contraindicated, ineffective or induce adverse effects. Dupilumab, a new treatment recently approved in Europe for patients with moderate SIGNIFICANCE Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated impressive clinical ef- fect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated conjunctivitis was reported in a minority of patients. We describe 10 patients treated with dupilumab where eye complications where common, suggesting the importance of close collaboration with an ophthalmologist. This is especially warranted among pa- tients with severe, long-lasting atopic dermatitis and/or previous eye disease. to severe AD, has shown promising results in clinical trials (3). Dupilumab is a human monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signalling through blockade of the shared IL-4α subunit (4). There are limited data on the efficacy and safety when switching from conventional systemic treatment to dupilumab and on long-term follow-up. We report here a case series of 10 patients with severe, long-lasting AD treated with dupilumab, in whom adverse events concerning the eyes were frequent. PATIENTS AND METHODS The study included a total of 10 patients (1 woman, 9 men; age range 23–59 years) with severe AD who were being treated with dupilumab (Dupixent ® , Sanofi-Aventis Groupe, Paris, France) (Table I). All participants had a history of asthma and/or allergic rhinoconjunctivitis and 3 had filaggrin mutations. All had been given systemic treatment on and off for at least 4 years. Some had tried more than one systemic treatment (MTX, cyclosporine, azathioprine or psoralen plus ultraviolet A (PUVA)) due to lack of response and/or adverse effects. All had been given periodic UV treatment. Six of 10 patients had been on MTX, and 3 of 10 had been on cyclosporine before switching to dupilumab. The patients were also given concomitant topical therapy (glucocorticoids, calcineurin inhibitors, moisturizers). Baseline values were assessed after a washout period of at least 2 weeks for the previous systemic treatment. The patients started with a loading dose of 600 mg dupilumab injected subcutaneously, followed by biweekly injections of 300 mg. Topical therapy was continued during washout and subsequently. The following variables were monitored during dupilumab thera­ py: Eczema Area and Severity Index (EASI) (5), visual analogue scale for pruritus (10 cm VAS), Montgomery-Åsberg Depression Rating Scale (MADRS) (6), Patient-Oriented Eczema Measure (POEM) (5) and Dermatology Life Quality Index (DLQI) (7). The reductions in EASI scores after 1, 3 and 5–7 months of treatment were expressed in terms of EASI-90, EASI-75 and EASI-50, i.e. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3121 Acta Derm Venereol 2019; 99: 375–378