Dupilumab effective, safe for moderate-to-severe AD in adults, adolescents
Patients with moderate-to-severe atopic dermatitis (AD) were more likely to have clinically meaningful responses when treated with dupilumab at doses of 300 mg either weekly or every 2 weeks compared with those on placebo, according to a post hoc analysis of the phase III SOLO 1 and SOLO 2* trials presented as a poster at AAD 2019.
Trial participants were 1,379 adult patients with chronic, moderate-to-severe AD who were unable to receive or had poor disease control with topical medications. They were randomized to receive placebo (n=460, mean age 38.4 years, 54.3 percent male) or subcutaneous dupilumab at doses of 300 mg QW (n=462, mean age 38.2 years, 60.8 percent male) or Q2W (n=457, mean age 38.3 years, 58.4 percent male) for 16 weeks.
At week 16, patients who received dupilumab QW or Q2W had better responses in one or more of the three AD domains assessed (≥50 percent reduction from baseline in EASI** [EASI-50], ≥3-point improvement from baseline in weekly average of daily peak pruritus NRS*** score, and ≥4-point improvement from baseline in DLQI# score) with 70.1 and 76.6 percent of patients who received dupilumab QW or Q2W, respectively, achieving clinically meaningful responses compared with 35.0 percent of patients on placebo (p<0.0001 for each comparison vs placebo). [AAD 2019, abstract 10198]
The benefits of dupilumab over placebo were evident as early as week 1 into treatment with 50.9 percent of patients on dupilumab QW and 48.1 percent of patients on dupilumab Q2W achieving clinically meaningful responses compared with 30.2 percent of patients on placebo (p<0.0001 for each comparison vs placebo).
Treatment-emergent adverse events (TEAEs) occurred at a similar rate between dupilumab QW, dupilumab Q2W, and placebo recipients (68.13, 70.32, and 70.18 percent, respectively). Injection-site reactions were more frequent among dupilumab QW or Q2W compared with placebo recipients (15.82, 10.97, and 6.14 percent, respectively), as was conjunctivitis (7.25, 9.68, and 2.19 percent, respectively).
Seven patients each on placebo and dupilumab QW, and six patients on dupilumab Q2W permanently discontinued treatment due to TEAEs.
In a separate phase III trial, 251 adolescents (aged 12–17 years) with moderate-to-severe AD were randomized to receive subcutaneous dupilumab Q2W (200 mg for weight <60 kg and 300 mg for weight ≥60 kg; n=82), dupilumab 300 mg Q4W (n=84), or placebo (n=85) for 16 weeks.
At week 16, more patients who received dupilumab Q2W or Q4W achieved Investigator’s Global Assessment (IGA) 0 or 1 than those who received placebo (24.4 percent and 17.9 percent vs 2.4 percent; p<0.001 vs placebo) as well as ≥75 percent improvement from baseline in EASI (EASI-75; 41.5 percent and 38.1 percent vs 8.2 percent; p<0.001 vs placebo). [AAD 2019, abstract 10051]
Percentage change from baseline to week 16 for EASI, SCORAD##, and weekly average of peak pruritus NRS scores also favoured the dupilumab regimens (p<0.001 for all comparisons vs placebo).
TEAEs occurred at a comparable rate between groups. Injection-site reactions occurred more frequently in dupilumab Q2W and Q4W than placebo recipients (8.5 percent and 6.0 percent vs 3.5 percent), as did conjunctivitis (9.8, 10.8, and 4.7 percent, respectively), while non-herpetic skin infections were more common in placebo recipients (18.8 percent) compared with dupilumab Q2W or Q4W recipients (9.8 and 9.6 percent, respectively).
There were no treatment discontinuations in either of the dupilumab groups, with the one serious TEAE and one discontinuation occurring in placebo recipients.
“[D]upilumab treatment resulted in statistically significant and clinically meaningful improvements in AD signs and symptoms … and quality of life [with] the Q2W regimen numerically superior to the Q4W regimen [for most categorical endpoints],” said the researchers.
The safety profile of dupilumab in adolescents was similar to that in the adult population with moderate-to-severe AD, they added.