Dupilumab an alternative for children with severe AD
The addition of the monoclonal antibody dupilumab to a standard topical corticosteroid (TCS) regimen led to significant improvements in scoring AD (SCORAD*) and its components, as well as EASI** scores, in children with severe atopic dermatitis (AD), according to data from the phase III LIBERTY AD PEDS trial presented at PAS 2021.
AD manifests with distinct distribution patterns across different age groups, with lesions usually involving large body surface areas (BSA). AD is usually accompanied by pruritus and sleep deprivation, which impairs quality of life especially in severe cases. [Br J Dermatol 2006;155:145-151]
Evidence has shown the efficacy and safety of dupilumab in adults and adolescents with moderate-to-severe AD, as well as in children aged ≥6 to <12 years with moderate-to-severe AD that does not respond well with topical therapies. [Am J Clin Dermatol 2020;21:567-577; JAMA Dermatol 2020;156:44-56; J Am Acad Dermatol 2020; 83:1282-1293]
This double-blind study randomized 367 children aged ≥6 to <12 years 1:1:1 to receive either SC dupilumab 100/200 mg Q2W (for a baseline weight of <30/≥30 kg; loading dose 200/400 mg) or 300 mg Q4W (regardless of weight; loading dose 600 mg), or placebo for 16 weeks on top of medium-potency TCS.
Only findings for FDA-approved doses – 300 mg Q4W (for children with baseline weight <30 kg [n=122; arm A]) and 200 mg Q2W (for children with baseline weight ≥30 kg [n=121; arm B]) – and weight-matched placebo were presented.
As early as week 1, reductions in total SCORAD scores were seen with dupilumab vs placebo, both in arm A (least-squares mean [LSM], 59.5 vs 64.4; p<0.05) and arm B (LSM, 58.7 vs 62.4). These continued to drop by week 2, signifying continued improvement with dupilumab in both arm A (LSM, 49.0 vs 59.2; p<0.0001) and arm B (LSM, 51.5 vs 60.7; p<0.01). [PAS 2021, abstract 6]
By week 16, compared with placebo, SCORAD scores were halved with dupilumab in both arm A (LSM, 25.5 vs 52.6) and arm B (LSM, 27.5 vs 50.0; p<0.0001 for both). The scores with dupilumab in arms A and B were also a far jump from the respective baseline LSM scores of 75.5 and 71.2.
Similarly, week 16 saw significant improvements in the dupilumab vs the placebo arm across various SCORAD subcomponents, such as BSA affected by AD (LSM, 15.9 vs 35.0), objective SCORAD (LSM, 21.4 vs 42.6), SCORAD pruritus VAS*** (LSM, 2.3 vs 5.0), and SCORAD sleep loss VAS (LSM, 2.0 vs 4.6; p<0.0001 for all) in arm A. A similar trend was seen in arm B (LSM, 17.5 vs 36.6, 24.1 vs 40.9, 2.0 vs 5.1, and 1.4 vs 3.8; p<0.0001 for all).
It should also be noted that the improvements in all subcomponents manifested as early as week 1, and continuously dropped through week 16.
EASI regional scores
LSM percent changes in EASI scores were greater with dupilumab vs placebo across all regions evaluated, be it in arm A (−72.3 vs −39.9 [head and neck], −87.5 vs −46.1 [trunk], −83.2 vs −38.7 [upper extremities], and −84.2 vs −40.0 [lower extremities]) or arm B (−79.2 vs −34.1, −86.5 vs −46.0, −78.8 vs −38.7, and −77.1 vs −40.5, respectively; p<0.0001 for all). The improvements with dupilumab were seen in most regions as early as week 2. [PAS 2021, abstract 7]
Subjective, objective improvements
“[Taken together, these findings suggest that] dupilumab + TCS resulted in a significant reduction in BSA affected by AD, and rapid improvements in AD signs [across all anatomic regions], pruritus, and sleep loss as assessed by total SCORAD score and SCORAD subcomponents [in this patient setting],” said the researchers.
Both studies reflected a safety profile that correlated with the known safety profile of dupilumab, with most adverse events being injection site reactions and conjunctivitis.