Efficacy and safety of dupilumab in Japanese adults with moderate-to-severe atopic dermatitis: a subanalysis of three clinical trials

Abstract

Background: Dupilumab, a human monoclonal antibody, blocks the shared receptor unit for interleukin-4 and interleukin-13. International phase II and III studies have evaluated the efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis (AD), but the effects of dupilumab in Japanese patients have not been reported.

Objectives: To evaluate the efficacy and safety of dupilumab in Japanese patients with moderate-to-severe AD.

Methods: We analysed the efficacy and safety of dupilumab in the Japanese cohorts of a 16-week, phase IIb dose-finding trial (AD-1021; NCT01859988); a 16-week, phase III, placebo-controlled monotherapy trial (LIBERTY AD SOLO 1; NCT02277743) and a 52-week, phase III, placebo-controlled study of dupilumab with topical corticosteroids (LIBERTY AD CHRONOS; NCT02260986).

Results: Twenty-seven, 106 and 117 Japanese patients were enrolled in AD-1021, SOLO 1 and CHRONOS, respectively. Baseline disease severity was numerically higher in the Japanese cohort than in the overall study population. Generally, dupilumab significantly improved signs and symptoms of AD, including pruritus and patient quality of life, compared with placebo in the Japanese cohort, consistent with the overall study population. The combined safety profile of dupilumab in the Japanese cohort was similar to that in the total study populations; dupilumab was associated with an increased incidence of injection-site reactions and conjunctivitis compared with placebo. Dupilumab was associated with rapid reduction in thymus and activation-regulated chemokine and gradual IgE reductions.

Conclusions: Dupilumab alone or with topical corticosteroids improved signs and symptoms of AD, had an acceptable safety profile, and suppressed biomarkers of type 2 inflammation compared with placebo in Japanese adult patients with moderate-to-severe AD. What's already known about this topic? Differences in atopic dermatitis (AD) pathology have been reported between Asian and Western populations, in which distinct helper T-cell activation profiles have been observed. International clinical studies in adults with moderate-to-severe AD have evaluated the efficacy and safety of dupilumab, which blocks interleukin-4 and interleukin-13, key molecules in type 2 inflammation. The effects of dupilumab in Japanese patients specifically have not yet been reported. What does this study add? Dupilumab alone or with topical corticosteroids improved signs and symptoms of AD and had an acceptable safety profile compared with placebo in Japanese patients with moderate-to-severe AD. The effects were comparable with those observed in the overall study population. Reported immunological differences in AD pathology in Asian patients may be secondary to type 2 immune activation.

Figure 1

Efficacy outcomes in the Japanese cohort from SOLO 1, including (a) the proportion of patients achieving Investigator's Global Assessment (IGA) 0 or 1 at week 16 with ≥ 2‐point improvement from baseline, (b) the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Values in white font denote patient numbers (n/N). Patients with missing IGA or EASI score at each visit were considered nonresponders. Values after the first rescue treatment used were set to missing (censoring). qw, weekly; q2w, every 2 weeks.

Figure 2

Efficacy outcomes in the Japanese cohort from SOLO 1, including (a) the percentage change from baseline in Eczema Area and Severity Index (EASI 75) over time and (b) the percentage change from baseline in the weekly average of Peak Pruritus Numerical Rating Scale (NRS) over time. Values after the first rescue treatment used were set to missing (censoring). LS, least squares; qw, weekly; q2w, every 2 weeks.

Figure 3

Efficacy outcomes in the Japanese cohort from SOLO 1, including the proportions of patients with (a) ≥ 3‐point or (b) ≥ 4‐point improvement in weekly average Peak Pruritus Numerical Rating Scale (NRS) over time. Values after the first rescue treatment used were set to missing (censoring). qw, weekly; q2w, every 2 weeks.

Figure 4

Efficacy outcomes in the Japanese cohort from SOLO 1, including the proportions of patients with ≥ 4‐point improvement in (a) Patient‐Oriented Eczema Measure (POEM) and (b) Dermatology Life Quality Index (DLQI) over time. Values after the first rescue treatment used were set to missing (censoring). POEM and DLQI analyses were performed in the subgroup of patients with respective baseline scores ≥ 4. LS, least squares; qw, weekly; q2w, every 2 weeks.

Figure 5

Efficacy outcomes in the Japanese cohort from CHRONOS, including (a) the proportion of patients achieving Investigator's Global Assessment (IGA) 0 or 1 at weeks 16 and 52 and with ≥ 2‐point improvement from baseline and (b) the proportions of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at weeks 16 and 52. Values in white font denote patient numbers (n/N). Values after the first rescue treatment used were set to missing (censoring). Patients with missing IGA or EASI scores at each visit were considered nonresponders. Statistical analyses at week 16 were based on the primary analysis dataset. qw, weekly; q2w, every 2 weeks; TCS, topical corticosteroids.

Figure 6

Efficacy outcomes in the Japanese cohort from CHRONOS, including (a) the percentage change from baseline in Eczema Area and Severity Index (EASI) over time and (b) the percentage change from baseline in the weekly average Peak Pruritus Numerical Rating Scale (NRS) over time. Values after the first rescue treatment used were set to missing (censoring). Statistical analyses at week 16 were based on the full analysis dataset. LS, least squares; qw, weekly; q2w, every 2 weeks; TCS, topical corticosteroids.

Figure 7

Efficacy outcomes in the Japanese cohort from CHRONOS, including the proportions of patients with (a) ≥ 3‐point or (b) ≥ 4‐point improvement in weekly average Peak Pruritus Numerical Rating Scale (NRS) over time. Values after the first rescue treatment used were set to missing (censoring). Statistical analyses at week 16 were based on the full analysis dataset. qw, weekly; q2w, every 2 weeks; TCS, topical corticosteroids.

Figure 8

Efficacy outcomes in the Japanese cohort from CHRONOS, including the proportions of patients with ≥ 4‐point improvement in (a) Patient‐Oriented Eczema Measure (POEM) and (b) Dermatology Life Quality Index (DLQI) over time. Values after the first rescue treatment used were set to missing (censoring). POEM and DLQI analyses were performed in the subgroup of patients with respective baseline scores ≥ 4. Statistical analyses at week 16 were based on the full analysis dataset. qw, weekly; q2w, every 2 weeks.