Acta Dermato-Venereologica 99-10CompleteContent | Page 7

CLINICAL REPORT 851 Dupilumab Versus Cyclosporine for the Treatment of Moderate- to-Severe Atopic Dermatitis in Adults: Indirect Comparison Using the Eczema Area and Severity Index Lieneke F. M. ARIENS 1 , Abhijit GADKARI 2 , Harmieke VAN OS-MEDENDORP 1 , Rajeev AYYAGARI 3 , Emi TERASAWA 3 , Andreas KUZNIK 2 , Zhen CHEN 2 , Gaëlle BÉGO-LE BAGOUSSE 4 , Yufang LU 2 , Elena RIZOVA 5 , Neil M. H. GRAHAM 2 , Gianluca PIROZZI 5 , Marjolein DE BRUIN-WELLER 1# , and Laurent ECKERT 4# 1 University Medical Center Utrecht, Utrecht, The Netherlands, 2 Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, 3 Analysis Group, Inc., New York, NY, USA, 4 Sanofi, Chilly-Mazarin, France, and 5 Sanofi, Bridgewater, NJ, USA # Co-last authors. Dupilumab is approved for uncontrolled moderate-to- severe atopic dermatitis (AD); cyclosporine is appro- ved for severe AD for ≤ 1 year. The efficacy/effecti- veness of these treat­ments was compared indirectly. Regression models used pooled patient-level data to estimate response (Eczema Area and Severity Index [EASI] EASI-50/EASI-75 at weeks 12–16 and 24– 30) to dupilumab 300 mg every 2 weeks (CHRONOS [NCT02260986]) or cyclosporine (University Medical Center). Models were adjusted for sex, baseline EASI, and thymus and activation-regulated chemokine level. A total of 106 patients received dupilumab (+ topical cortico­steroids; + TCS), and 57 received cyclosporine (+ TCS). Among University Medical Center patients, estimated EASI-50 responders were, dupilumab vs. cyclosporine, 91% vs. 77% (p  = 0.038; weeks 12–16), and 96% vs. 67% (p  < 0.0001; weeks 24–30); EASI- 75 responders were 78% vs. 56% (p  = 0.016; weeks 12–16) and 80% vs. 47% (p  <0.001; weeks 24–30). Among CHRONOS patients, estimated EASI-50 respon- ders were 90% vs. 74% (p  <0.038; weeks 12–16) and 92% vs. 53% (p  < 0.0001; weeks 24–30); EASI-75 re- sponders were 75% vs. 52% (p  = 0.016; weeks 12–16) and 74% vs. 40% (p  <0.001; weeks 24–30), respecti- vely. These results suggest a higher relative efficacy of dupilumab vs. cyclosporine. Key words: adult; atopic dermatitis; cyclosporine; dupilumab; eczema; Eczema Area and Severity Index. Accepted May 16, 2019; E-published May 17, 2019 Acta Derm Venereol 2019; 99: 851–857. Corr: Marjolein de Bruin-Weller, University Medical Center Utrecht, Heidelberglaan 100, NL-3584 CX Utrecht, The Netherlands. E-mail: [email protected] A topic dermatitis (AD) is a common chronic inflam- matory skin disease, which is prone to disease exacerbations. In adults, the estimated prevalence of AD is between 2% and 5%, depending on region (1). In the majority of patients, AD can be treated adequately with topical agents and/or ultraviolet (UV) light (2). However, in a subpopulation of patients with moderate-to-severe AD, the disease remains inadequately controlled despite these treatments, with patients still experiencing signs SIGNIFICANCE Dupilumab is approved for uncontrolled moderate-to-se- vere atopic dermatitis; cyclosporine is approved for severe atopic dermatitis. Efficacy/effectiveness were compared in- directly using regression models. Estimated response was evaluated using 50% improvement in Eczema Area and Severity Index (EASI-50) and 75% improvement (EASI- 75) at weeks 12–16 and 24–30 to dupilumab (data from CHRONOS study) or cyclosporine (data from University Medical Center; UMC). For UMC patients, EASI-50 respon- ders were, dupilumab vs. cyclosporine, 91% vs. 77% at weeks 12–16, and 96% vs. 67% at weeks 24–30; EASI-75 responders were 78% vs. 56% at weeks 12–16, and 80% vs. 47% at weeks 24–30. For CHRONOS, EASI-50 respon- ders were 90% vs. 74% at weeks 12–16 and 92% vs. 53% at weeks 24–30; EASI-75 responders were 75% vs. 52% at weeks 12–16, and 74% vs. 40% at weeks 24–30, re- spectively. These results suggest a higher relative efficacy of dupilumab vs. cyclosporine. (e.g. lesions, redness) and symptoms (e.g. itch, sleep disturbance). For these patients, systemic immunomo- dulating treatment is indicated. The decision to start systemic medication should be based on the severity of skin lesions; symptoms such as itch, pain, and sleep disturbance; and the impact on quality of life (2). Cyclosporine A is the only oral immunosuppressant approved for the treatment of severe AD in some Euro- pean countries and in Japan (3, 4). The clinical efficacy of cyclosporine in moderate-to-severe AD was supported by a systematic review of 14 randomized controlled trials, although no conclusion could be drawn about long-term safety (5). Furthermore, many of the studies were con- ducted in the early 1990s, and well-validated efficacy outcome measures, such as the Eczema Area and Severity Index (EASI), had not yet been developed. In a more recent study of 356 patients with AD who were receiving long-term treatment with cyclosporine, nearly half of the patients cited lack of efficacy and/or side-effects as their reason for discontinuation of treatment (6). Treatment response to cyclosporine has been met with various le- vels of success (6, 7). Other immunosuppressant agents, including azathioprine and mycophenolate mofetil, are This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3219 Acta Derm Venereol 2019; 99: 851–857