One-year real-world clinical effectiveness, safety, and laboratory safety of dupilumab in Japanese adult patients with atopic dermatitis: A single-center retrospective study

Abstract

To the Editor: Dupilumab has demonstrated good efficacy and tolerable safety in adult patients with moderate to severe atopic dermatitis in the long term in clinical trials,1Deleuran M. Thaci D. Beck L.A. et al.Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study.J Am Acad Dermatol. 2020; 82: 377-388Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar but real-world long-term data are limited. The Asian atopic dermatitis phenotype differs from the European American atopic dermatitis phenotype by demonstrating increased T helper cell type 17 polarization in addition to T helper cell type 2 skewing,2Noda S. Suarez-Farinas M. Ungar B. et al.The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization.J Allergy Clin Immunol. 2015; 136: 1254-1264Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar suggesting a difference in responsiveness to dupilumab. We analyzed our 1-year actual data on Japanese adult atopic dermatitis patients treated with dupilumab. All atopic dermatitis patients who initiated dupilumab from June 2018 to August 2019 and were treated with dupilumab for more than 3 months at our hospital as of December 1, 2019, were included in this study. Dupilumab is approved in Japan only for adult patients with moderate to severe atopic dermatitis who were refractory to topical corticosteroid or tacrolimus for more than 6 months. Detailed inclusion criteria, dosage, and administration have been described previously.3Uchida H. Kamata M. Mizukawa I. et al.Real-world effectiveness and safety of dupilumab for the treatment of atopic dermatitis in Japanese patients: a single-centre retrospective study.Br J Dermatol. 2019; 181: 1083-1085Crossref PubMed Scopus (25) Google Scholar Patients whose clinical data or laboratory results were not described in their chart were excluded. Dermatologists from our department performed all assessments of patients and collected patient data. Sixty-one Japanese patients (51 men and 10 women) were included in this study. Their mean age was 37.7 years (range 17-61 years). Only 1 patient received any form of systemic therapy (cyclosporine) before initiating dupilumab. The mean baseline Eczema Area and Severity Index score was 32.7 (standard deviation 11.5). Table I summarizes the baseline demographics and clinical characteristics of the patients. In all patients, skin eruption improved greatly after initiation of dupilumab. Fig 1 shows the percentage changes in these parameters compared with the respective baseline values. The total Eczema Area and Severity Index score significantly decreased by a mean of 47.1% at 1 month, 70.4% at 3 months, 75.6% at 6 months, and 76.5% at 12 months after initiation of dupilumab. Other clinical severity scores and quality-of-life scores improved at 1, 3, 6, and 12 months. Laboratory results showed tolerable safety and improvement of biomarkers except circulating eosinophils.Table IBaseline demographics and clinical characteristics of atopic dermatitis patients who were treated with dupilumab at our hospitalCharacteristicMean ± standard deviation or no. (%)(normal range)Age, y37.7 ± 11.6SexMen, 51; women, 10Height, cm166.9 ± 7.4Weight, kg63.3 ± 11.1BMI22.7 ± 20.9Disease duration, y29.5 ± 14.3IGA3.6 ± 0.5EASI score32.7 ± 11.5EASI score of head and face3.5 ± 1.9Affected BSA, %65.7 ± 20.9DLQI score11.6 ± 5.9POEM score18.4 ± 6.8VAS score of pruritus60.4 ± 25.1Serum TARC level (pg/mL)3783.1 ± 4811.7 (<450)Serum IgE level (IU/mL)14,305 ± 20,530.2 (<100)Serum LDH level (U/L)269.8 ± 89.6 (124–222)No. of circulating WBCs (/μL)6675.4 ± 1830 (3300–8600)No. of circulating eosinophils (/μL)527.1 ± 376 (66–344)No. of circulating neutrophils (/μL)4325.2 ± 1662.7 (1683–5762)Platelet count (×103/μL)278.2 ± 64.8 (158–348)Presence of or a history of asthma30/61 (including having a childhood history of asthma)BMI, Body mass index; BSA, body surface area; DLQI, Dermatology Quality of Life Index; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; IgE, immunoglobulin E; LDH, lactate dehydrogenase; POEM, Patient-Oriented Eczema Measure; TARC, thymus and activation-regulated chemokine; VAS, visual analog scale; WBC, white blood cells. Open table in a new tab BMI, Body mass index; BSA, body surface area; DLQI, Dermatology Quality of Life Index; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; IgE, immunoglobulin E; LDH, lactate dehydrogenase; POEM, Patient-Oriented Eczema Measure; TARC, thymus and activation-regulated chemokine; VAS, visual analog scale; WBC, white blood cells. As for adverse effects, conjunctivitis was observed in 13 patients (21.3%), 5 of whom had a history of allergic conjunctivitis. Conjunctivitis was associated with higher baseline serum levels of immunoglobulin E and thymus and activation-regulated chemokine but not with clinical severity.4Uchida H. Kamata M. Nagata M. et al.Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with higher baseline serum levels of immunoglobulin E and thymus and activation-regulated chemokine but not clinical severity in a real-world setting.J Am Acad Dermatol. 2020; 82: 1247-1249Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar No patient discontinued dupilumab therapy because of dupilumab-associated conjunctivitis. In some patients, skin manifestation on the face was refractory to dupilumab treatment despite considerable improvement on the trunk and extremities. No other safety concerns were detected. Our study revealed that in an actual setting, dupilumab showed effectiveness and safety with tolerable effects on laboratory parameters in Japanese adult atopic dermatitis patients in the long term. The phase 3 open-label extension study conducted in North American (50.5%), European (36.8%), and Asia-Pacific (12.7%) countries reported that the mean percentage change in Eczema Area and Severity Index score from the baseline of the parent study was −89.0% and −90.0% at weeks 52 and 76, respectively,1Deleuran M. Thaci D. Beck L.A. et al.Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study.J Am Acad Dermatol. 2020; 82: 377-388Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar whereas it was –76.5% at 12 months in our study. This suggests the possibility of slightly poorer long-term response to dupilumab in an actual setting rather than in clinical trials, or in Japanese patients compared with North American and European ones.