Findings of the 52-week phase 3 LIBERTY AD PED-OLE trial showed dupilumab to have an adequate safety profile and incremental clinical benefit with continued use among pediatric patients with moderate to severe atopic dermatitis.
Dupilumab demonstrated significant long-term efficacy and an adequate safety profile in pediatric patients with atopic dermatitis (AD), in which incremental clinical benefits were observed with continued use. Findings were published recently in the American Journal of Clinical Dermatology.
Designed as a fully human monoclonal antibody that blocks 2 key and central drivers of type 2 inflammation (interleukin [IL]-4 and IL-13), dupilumab has been shown in prior studies to provide substantial improvement in AD signs, symptoms, and quality of life, compared with placebo, in adolescent patients.
However, researchers note that long-term data on the approved dose regimen of dupilumab for adolescents with AD are currently lacking, as well as whether the continuous use of dupilumab over a long period can lead to sustained clear or almost clear skin (Investigator’s Global Assessment [IGA] score of 0 or 1).
“A substantial proportion of adolescents have persistent disease, and patients with higher severity of disease have been shown to have lower rates of remission,” said the study authors.
They conducted an open-label extension (OLE) study to assess the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate to severe AD who had participated in dupilumab parent trials and were subsequently enrolled in the LIBERTY AD PED-OLE study (NCT02612454).
Participants were initiated on dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, in which those with an inadequate clinical response (IGA score of 0 or 1 was not reached) to the regimen were then uptitrated to the FDA approved weight-tiered dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively) for up to 52 weeks.
“Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required,” noted researchers.
The primary endpoints assessed were the incidence and rate of treatment-emergent adverse events (TEAEs), with secondary efficacy outcomes including the proportion of patients with an IGA score of 0/1 (clear/almost clear) by visit through week 52 and the proportion of patients achieving Eczema Area and Severity Index (EASI)-50/-75/-90 (≥ 50; ≥ 75%; ≥ 90% reduction, respectively, in EASI from baseline of parent study) by visit through week 52.
A total of 294 patients were included in the analysis (mean age, 14.7 years; 69% White; 56.8% male), of which 102 (34.7%) had completed the 52-week visit at the database lock. A majority of participants had moderate to severe disease at baseline, with 47.3% and 24.8% reporting IGA scores of 3 and 4, respectively.
By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in EASI. Most (70.9%) of the study cohort required uptitration to the approved dupilumab dose regimen—35.7% and 51.9% of uptitrated patients achieved an IGA score of 0/1 or 75% improvement in EASI, respectively, at 48 weeks after the first uptitration visit. The proportion of patients achieving these efficacy endpoints increased over time.
Across the 52-week study period, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication. More than half of these patients (56.7%) relapsed and were subsequently re-initiated on treatment, with a mean (SD) time to re-initiation of 17.5 (17.3) weeks.
Safety analyses indicated that the long-term safety profile of dupilumab was comparable with that observed in adults and consistent with prior data. Most treatment-emergent adverse events were mild to moderate, with the most frequently reported being nasopharyngitis (20.4%; 23.6 patients per 100 patient-years), AD (19.0%; 21.3 patients per 100 patient-years), upper respiratory tract infection (11.9%; 12.5 patients per 100 patient-years), and headache (8.8%; 9.3 patients per 100 patient-years).
“The need for uptitration in most patients during the course of the study to the approved q2w regimen suggests that this regimen is optimal for adolescent patients with AD,” concluded the study authors. “The majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy.”
Blauvelt A, Guttman‑Yassky E, Paller AS, et al. Long‑term efficacy and safety of dupilumab in adolescents with moderate‑to‑severe atopic dermatitis: Results through week 52 from a phase III open‑label extension trial (LIBERTY AD PED‑OLE). Am J Clin Dermatol. Published online May 14, 2022. doi:10.1007/s40257-022-00683-2