Dupilumab Shows High Effectiveness in AD for Ages 6 Months and Up

Dupilumab (Dupixent) is an effective and safe therapeutic option for patients aged 6 months to adulthood who have moderate-to-severe atopic dermatitis (AD), according to 3 abstracts presented at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

With limited treatment options for moderate-to-severe AD, dupilumab has previously demonstrated significant efficacy and an acceptable safety profile in adults, adolescents, and children aged 6 years and older. However, pediatric patients aged 6 months to 5 years have been cited as a major unmet populations in AD management.

Presenting phase 3 efficacy and safety data of dupilumab in these pediatric patient populations, researchers of the first abstract examined children aged 6 months to 5 years with moderate-to-severe AD of the Liberty AD INFANTS/PRE-SCHOOL double-blind, placebo-controlled trial.¹

These patients, who were inadequately controlled with topical therapies, were randomized 1:1 to subcutaneous dupilumab every 4 weeks (200 mg if baseline weight ≥ 5 to < 15 kg; 300 mg if ≥ 15 to < 30 kg; randomization stratified by weight) or placebo for 16 weeks (N = 162).

“From day 14, all patients initiated standardized treatment with low-potency topical corticosteroids (TCS). The primary endpoint was proportion of patients with an Investigator’s Global Assessment (IGA) score of 0 or 1  (clear/almost clear) at Week 16, and the co-primary endpoint was proportion of patients with 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) at Week 16,” noted researchers.

Secondary outcomes included percent change in EASI and percent change in weekly averaged worst scratch/itch score at week 16.

Of the 157 randomized pediatric participants who completed 16 weeks of treatment, significantly more patients who received dupilumab achieved an IGA score of 0-1 (27.7% vs 3.9%; P < .0001) and EASI-75 (53.0% vs 10.7%; P < .0001), compared with those given placebo.

Moreover, least-squares mean percent change [SD] from baseline to week 16 in EASI was significantly lowered in patients randomized to dupilumab vs placebo (–70.0% (4.9) vs –19.6% (5.1); P < .0001), as was the weekly averaged worst scratch/itch score (–49.4% [5.0]  vs –2.2% [5.2]; P < .0001). A favorable safety profile similar to that found in adults and older children administered dupilumab was also observed.

In the second abstract, research involving children aged 6 to 11 years with inadequately controlled severe AD presented long-term data for 321 participants (mean [SD] age, 8.6 [1.7] years; mean [SD] AD duration, 7.4 [2.2 ] years) of the 16 week, double-blind, phase 3 LIBERTY AD PEDS open-label extension (OLE) study.²

For the study, patients enrolled in the OLE were treated with 300 mg dupilumab every 4 weeks. If treatment response was inadequate, defined as failure to achieve an IGA score of 0/1 within 16 weeks of treatment initiation, treatment was said to be potentially up-titrated to 200 mg or 300 mg every 2 weeks (for patients weighing <60 kg or ≥ 60 kg, respectively).

Across the cohort, mean percentage change (SD) from parent study baseline (PSBL) to OLE baseline in EASI was −62.5 (34.4). Compared with PSBL, significant improvements were observed across several endpoints:

• Improvements in mean percentage change from PSBL in EASI observed at week 16 (−79.6 [20.8]) and week 52 (−86.0 [13.9]) of the OLE baseline
• Increase in the proportion of patients achieving EASI reduction at OLE baseline of 50% or greater (EASI-50, 71.7%) and 75% or greater (EASI-75, 210/257 [81.7%] to week 52 of OLE (EASI-50, 97.3%; EASI-75, 81.7%)
• Proportion of patients achieving an IGA score of 0 or 1 increased from the OLE baseline (19.3%) to week 52 (40.5%)

“The long-term safety profile of dupilumab was acceptable and consistent with that previously seen in shorter term, placebo-controlled studies,” noted authors.

Lastly, the third abstract presented long-term data on the efficacy of dupilumab in adults aged 18 and older with moderate-to-severe AD.³

Recruiting all patients who had participated in any dupilumab parent study (phase 1 to 3), the initial duration of the LIBERTY AD OLE was 3 years and up to 5 years in certain countries. Patients were treated with 300 mg dupilumab weekly during the OLE, which transitioned to 300 mg every 2 weeks in 2019 to align with approved dosage.

Of the 2677 patients who enrolled in the OLE, 2207 completed treatment up to week 52, 1065 up to week 100, 557 up to week 148, 362 up to week 172, 352 up to week 204, and 240 to week 204 and beyond.

Compared with rom PSBL, 91% of patients achieved EASI-75 and 76% of patients achieved a 90% reduction in EASI at week 204. Moreover, 70.8% of patients achieved a 4-point or greater reduction in the Peak Pruritus Numerical Rating Scale score from PSBL.

“A total of 2273 (84.9%) patients reported treatment-emergent adverse events, and 99 (3.7%) patients discontinued treatment permanently due to reported adverse events,” noted researchers. “Dupilumab had an acceptable safety profile.”

References

1. Paller AS, Simpson EL, Siegfried EC, et al. Efficacy and safety of dupilumab in children aged ≥ 6 months to < 6 years with moderate-to-severe atopic dermatitis. Presented at: RAD 2021; December 11-13, 2021.

2. Paller AS, Cork MJ, Siegfried EC, et al. Efficacy and safety of dupilumab in children aged 6–11 years with inadequately controlled severe atopic dermatitis: Results from an open-label extension trial up to 1 year. Presented at: RAD 2021; December 11-13, 2021.

3. Thyssen JP, Blauvelt A, Lockshin B, et al. Dupilumab provides long-term eficacy for up to 4 years in an open-label extension study of adults with moderate-to-severe atopic dermatitis. Presented at RAD 2021; December 11-13, 2021.