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

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.

Figure 1

Outcomes in patients with Investigator's Global Assessment > 1 treated with dupilumab or placebo. (a) Percentage change from baseline to week 16 in Eczema Area and Severity Index (EASI) total score. (b, c) Proportions of patients who achieved ≥ 75% improvement in EASI (EASI 75) (b) or EASI 50 (c) at week 16. (d) Percentage change from baseline to week 16 in peak pruritus numerical rating scale (NRS) score. (e) Proportion of body surface area (BSA) affected by atopic dermatitis (AD). Error bars indicate standard error (SE). LOCF, last observation carried forward; LS, least squares; q2w, every 2 weeks. *P < 0·001 vs. placebo.

Figure 2

Outcomes in patients with Investigator's Global Assessment > 1 treated with dupilumab or placebo. (a) Change from baseline to week 16 in Dermatology Life Quality Index (DLQI) total score. (b) Proportion of patients with ≥ 4‐point reduction in DLQI score from baseline. (c) Change from baseline to week 16 in Patient‐Oriented Eczema Measure (POEM) score. (d) Proportion of patients with ≥ 4‐point reduction in POEM score from baseline. Error bars indicate the standard error. LOCF, last observation carried forward; LS, least squares; q2w, every 2 weeks. *P < 0·001 vs. placebo.

Figure 3

Illustration of a patient who improved from Investigator's Global Assessment (IGA) 4 (severe) at baseline to IGA 2 (mild) after 16 weeks of dupilumab treatment. Change in IGA score was accompanied by clinically meaningful improvement in BSA, symptoms (sleep, pruritus, POEM) and quality of life. BSA, body surface area; DLQI, Dermatitis Life Quality Index; EASI, Eczema Area and Severity Index; POEM, Patient‐Oriented Eczema Measure.