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