Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment

a pooled analysis of data from two phase III trials

J. I. Silverberg, Eric Simpson, M. Ardeleanu, D. Thaçi, S. Barbarot, J. Bagel, Z. Chen, L. Eckert, J. Chao, A. Korotzer, E. Rizova, A. B. Rossi, Y. Lu, N. M.H. Graham, T. Hultsch, G. Pirozzi, B. Akinlade

Research output: Contribution to journalArticle

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Abstract

Background: In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objectives: To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods: LIBERTY AD SOLO 1 and 2 were two 16-week, randomized, double-blind trials enrolling adult patients with moderate-to-severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. Results: At week 16, 278 of 449 dupilumab q2w-treated patients (median age 36·0 years) and 396 of 443 placebo-treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (−48·9% vs. −11·3%, P < 0·001), pruritus NRS (−35·2% vs. −9·1%, P < 0·001), affected BSA (−23·1% vs. −4·5%, P < 0·001), POEM score ≥ 4-point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4-point improvement (59·3% vs. 24·4%, P < 0·001). Conclusions: In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects.

Original languageEnglish (US)
Pages (from-to)80-87
Number of pages8
JournalBritish Journal of Dermatology
Volume181
Issue number1
DOIs
StatePublished - Jul 1 2019

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Atopic Dermatitis
Research Personnel
Skin
Eczema
Placebos
Outcome Assessment (Health Care)
Quality of Life
SAR231893
Body Surface Area
Therapeutics
Pruritus
Dermatology
Signs and Symptoms
Clinical Trials

ASJC Scopus subject areas

  • Dermatology

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Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment : a pooled analysis of data from two phase III trials. / Silverberg, J. I.; Simpson, Eric; Ardeleanu, M.; Thaçi, D.; Barbarot, S.; Bagel, J.; Chen, Z.; Eckert, L.; Chao, J.; Korotzer, A.; Rizova, E.; Rossi, A. B.; Lu, Y.; Graham, N. M.H.; Hultsch, T.; Pirozzi, G.; Akinlade, B.

In: British Journal of Dermatology, Vol. 181, No. 1, 01.07.2019, p. 80-87.

Research output: Contribution to journalArticle

Silverberg, JI, Simpson, E, Ardeleanu, M, Thaçi, D, Barbarot, S, Bagel, J, Chen, Z, Eckert, L, Chao, J, Korotzer, A, Rizova, E, Rossi, AB, Lu, Y, Graham, NMH, Hultsch, T, Pirozzi, G & Akinlade, B 2019, 'Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from two phase III trials', British Journal of Dermatology, vol. 181, no. 1, pp. 80-87. https://doi.org/10.1111/bjd.17791
Silverberg, J. I. ; Simpson, Eric ; Ardeleanu, M. ; Thaçi, D. ; Barbarot, S. ; Bagel, J. ; Chen, Z. ; Eckert, L. ; Chao, J. ; Korotzer, A. ; Rizova, E. ; Rossi, A. B. ; Lu, Y. ; Graham, N. M.H. ; Hultsch, T. ; Pirozzi, G. ; Akinlade, B. / Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment : a pooled analysis of data from two phase III trials. In: British Journal of Dermatology. 2019 ; Vol. 181, No. 1. pp. 80-87.
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abstract = "Background: In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objectives: To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods: LIBERTY AD SOLO 1 and 2 were two 16-week, randomized, double-blind trials enrolling adult patients with moderate-to-severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. Results: At week 16, 278 of 449 dupilumab q2w-treated patients (median age 36·0 years) and 396 of 443 placebo-treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (−48·9{\%} vs. −11·3{\%}, P < 0·001), pruritus NRS (−35·2{\%} vs. −9·1{\%}, P < 0·001), affected BSA (−23·1{\%} vs. −4·5{\%}, P < 0·001), POEM score ≥ 4-point improvement (57·4{\%} vs. 21·0{\%}, P < 0·001) and DLQI score ≥ 4-point improvement (59·3{\%} vs. 24·4{\%}, P < 0·001). Conclusions: In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects.",
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T1 - Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment

T2 - a pooled analysis of data from two phase III trials

AU - Silverberg, J. I.

AU - Simpson, Eric

AU - Ardeleanu, M.

AU - Thaçi, D.

AU - Barbarot, S.

AU - Bagel, J.

AU - Chen, Z.

AU - Eckert, L.

AU - Chao, J.

AU - Korotzer, A.

AU - Rizova, E.

AU - Rossi, A. B.

AU - Lu, Y.

AU - Graham, N. M.H.

AU - Hultsch, T.

AU - Pirozzi, G.

AU - Akinlade, B.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objectives: To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods: LIBERTY AD SOLO 1 and 2 were two 16-week, randomized, double-blind trials enrolling adult patients with moderate-to-severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. Results: At week 16, 278 of 449 dupilumab q2w-treated patients (median age 36·0 years) and 396 of 443 placebo-treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (−48·9% vs. −11·3%, P < 0·001), pruritus NRS (−35·2% vs. −9·1%, P < 0·001), affected BSA (−23·1% vs. −4·5%, P < 0·001), POEM score ≥ 4-point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4-point improvement (59·3% vs. 24·4%, P < 0·001). Conclusions: In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects.

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