Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: A randomised, placebo-controlled, dose-ranging phase 2b trial

Diamant Thaçi, Eric Simpson, Lisa A. Beck, Thomas Bieber, Andrew Blauvelt, Kim Papp, Weily Soong, Margitta Worm, Jacek C. Szepietowski, Howard Sofen, Makoto Kawashima, Richard Wu, Steven P. Weinstein, Neil M H Graham, Gianluca Pirozzi, Ariel Teper, E. Rand Sutherland, Vera Mastey, Neil Stahl, George D. YancopoulosMarius Ardeleanu

Research output: Contribution to journalArticle

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Abstract

Background Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite drivers of atopic dermatitis, evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to assess the efficacy and safety of several dose regimens of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments. Methods In this randomised, placebo-controlled, double-blind study, we enrolled patients aged 18 years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher at screening (≥16 at baseline) and inadequate response to topical treatments from 91 study centres, including hospitals, clinics, and academic institutions, in Canada, Czech Republic, Germany, Hungary, Japan, Poland, and the USA. Patients were randomly assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by Investigator's Global Assessment) and region (Japan vs rest of world) to receive subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2 weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16 weeks. We used a central randomisation scheme, provided by an interactive voice response system. Drug kits were coded, providing masking to treatment assignment, and allocation was concealed. Patients on treatment every 2 weeks and every 4 weeks received volume-matched placebo every week when dupilumab was not given to ensure double blinding. The primary outcome was efficacy of dupilumab dose regimens based on EASI score least-squares mean percentage change (SE) from baseline to week 16. Analyses included all randomly assigned patients who received one or more doses of study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988. Findings Between May 15, 2013, and Jan 27, 2014, 452 patients were assessed for eligibility, and 380 patients were randomly assigned. 379 patients received one or more doses of study drug (300 mg once a week [n=63], 300 mg every 2 weeks [n=64], 200 mg every 2 weeks [n=61], 300 mg every 4 weeks [n=65], 100 mg every 4 weeks [n=65]; placebo [n=61]). EASI score improvements favoured all dupilumab regimens versus placebo (p

Original languageEnglish (US)
Pages (from-to)40-52
Number of pages13
JournalThe Lancet
Volume387
Issue number10013
DOIs
StatePublished - Jan 2 2016

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Atopic Dermatitis
Placebos
Safety
Eczema
Therapeutics
Japan
Pharmaceutical Preparations
Interleukin-13
Hungary
Czech Republic
Poland
Random Allocation
SAR231893
Least-Squares Analysis
Double-Blind Method
Interleukin-4
Canada
Germany
Monoclonal Antibodies
Research Personnel

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments : A randomised, placebo-controlled, dose-ranging phase 2b trial. / Thaçi, Diamant; Simpson, Eric; Beck, Lisa A.; Bieber, Thomas; Blauvelt, Andrew; Papp, Kim; Soong, Weily; Worm, Margitta; Szepietowski, Jacek C.; Sofen, Howard; Kawashima, Makoto; Wu, Richard; Weinstein, Steven P.; Graham, Neil M H; Pirozzi, Gianluca; Teper, Ariel; Sutherland, E. Rand; Mastey, Vera; Stahl, Neil; Yancopoulos, George D.; Ardeleanu, Marius.

In: The Lancet, Vol. 387, No. 10013, 02.01.2016, p. 40-52.

Research output: Contribution to journalArticle

Thaçi, D, Simpson, E, Beck, LA, Bieber, T, Blauvelt, A, Papp, K, Soong, W, Worm, M, Szepietowski, JC, Sofen, H, Kawashima, M, Wu, R, Weinstein, SP, Graham, NMH, Pirozzi, G, Teper, A, Sutherland, ER, Mastey, V, Stahl, N, Yancopoulos, GD & Ardeleanu, M 2016, 'Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: A randomised, placebo-controlled, dose-ranging phase 2b trial', The Lancet, vol. 387, no. 10013, pp. 40-52. https://doi.org/10.1016/S0140-6736(15)00388-8
Thaçi, Diamant ; Simpson, Eric ; Beck, Lisa A. ; Bieber, Thomas ; Blauvelt, Andrew ; Papp, Kim ; Soong, Weily ; Worm, Margitta ; Szepietowski, Jacek C. ; Sofen, Howard ; Kawashima, Makoto ; Wu, Richard ; Weinstein, Steven P. ; Graham, Neil M H ; Pirozzi, Gianluca ; Teper, Ariel ; Sutherland, E. Rand ; Mastey, Vera ; Stahl, Neil ; Yancopoulos, George D. ; Ardeleanu, Marius. / Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments : A randomised, placebo-controlled, dose-ranging phase 2b trial. In: The Lancet. 2016 ; Vol. 387, No. 10013. pp. 40-52.
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T1 - Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments

T2 - A randomised, placebo-controlled, dose-ranging phase 2b trial

AU - Thaçi, Diamant

AU - Simpson, Eric

AU - Beck, Lisa A.

AU - Bieber, Thomas

AU - Blauvelt, Andrew

AU - Papp, Kim

AU - Soong, Weily

AU - Worm, Margitta

AU - Szepietowski, Jacek C.

AU - Sofen, Howard

AU - Kawashima, Makoto

AU - Wu, Richard

AU - Weinstein, Steven P.

AU - Graham, Neil M H

AU - Pirozzi, Gianluca

AU - Teper, Ariel

AU - Sutherland, E. Rand

AU - Mastey, Vera

AU - Stahl, Neil

AU - Yancopoulos, George D.

AU - Ardeleanu, Marius

PY - 2016/1/2

Y1 - 2016/1/2

N2 - Background Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite drivers of atopic dermatitis, evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to assess the efficacy and safety of several dose regimens of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments. Methods In this randomised, placebo-controlled, double-blind study, we enrolled patients aged 18 years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher at screening (≥16 at baseline) and inadequate response to topical treatments from 91 study centres, including hospitals, clinics, and academic institutions, in Canada, Czech Republic, Germany, Hungary, Japan, Poland, and the USA. Patients were randomly assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by Investigator's Global Assessment) and region (Japan vs rest of world) to receive subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2 weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16 weeks. We used a central randomisation scheme, provided by an interactive voice response system. Drug kits were coded, providing masking to treatment assignment, and allocation was concealed. Patients on treatment every 2 weeks and every 4 weeks received volume-matched placebo every week when dupilumab was not given to ensure double blinding. The primary outcome was efficacy of dupilumab dose regimens based on EASI score least-squares mean percentage change (SE) from baseline to week 16. Analyses included all randomly assigned patients who received one or more doses of study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988. Findings Between May 15, 2013, and Jan 27, 2014, 452 patients were assessed for eligibility, and 380 patients were randomly assigned. 379 patients received one or more doses of study drug (300 mg once a week [n=63], 300 mg every 2 weeks [n=64], 200 mg every 2 weeks [n=61], 300 mg every 4 weeks [n=65], 100 mg every 4 weeks [n=65]; placebo [n=61]). EASI score improvements favoured all dupilumab regimens versus placebo (p

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