Dupilumab Treatment in Pediatric Patients Aged 6-11 Years with Severe Atopic Dermatitis Whose Disease Is Not Adequately Controlled: A Review.
Ontology highlight
ABSTRACT:
SUBMITTER: Cork MJ
PROVIDER: S-EPMC10849907 | biostudies-literature | 2024
REPOSITORIES: biostudies-literature
Publications
Dupilumab Treatment in Pediatric Patients Aged 6-11 Years with Severe Atopic Dermatitis Whose Disease Is Not Adequately Controlled: A Review.
Cork Michael J MJ Danby Simon G SG Rossi Ana B AB Bansal Ashish A
Drug design, development and therapy 20240203
Atopic dermatitis (AD) is the most common inflammatory skin disease in children. Children with severe AD have a multidimensional disease burden characterized by skin lesions, itching, frequent infections, sleep deprivation, and a high rate of comorbidities. These impact the mental health and overall quality of life of not only the children but also of their parents and caregivers. There are few effective available treatment options for young children with severe AD that are suitable for long-ter ...[more]
Similar Datasets
Project description:BackgroundPrevious studies of dupilumab in adolescents and adults with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful adverse changes in laboratory parameters.ObjectiveThe aim of this study was to assess laboratory outcomes in children aged 6-11 years with severe AD in a randomized, placebo-controlled, phase III trial of dupilumab.MethodsChildren aged 6-11 years with severe AD were randomized 1:1:1 to 16 weeks of dupilumab 300 mg every 4 weeks, 100 or 200 mg every 2 weeks, or matching placebo, all with concomitant topical corticosteroids (TCS). Blood samples were collected at baseline and Weeks 4, 8, and 16; urine samples were collected at baseline and Weeks 4 and 16.ResultsOf 367 patients enrolled in the study, 362 were included in the safety analysis, 351 completed study treatment, and 4 withdrew due to treatment-emergent adverse events not related to laboratory abnormalities. Both dupilumab + TCS groups showed overall trends toward increases in mean blood levels of eosinophils and alkaline phosphatase, and decreases in mean blood levels of platelets, neutrophils, and lactate dehydrogenase levels, without corresponding mean changes in the placebo + TCS group. None of these changes were associated with symptoms or clinically meaningful adverse outcomes, and none led to treatment modification. No clinically significant changes or trends were observed for other measured laboratory parameters.ConclusionThere were no clinically meaningful adverse changes in routine laboratory parameters attributable to treatment with dupilumab + TCS. Changes in platelet counts and lactate dehydrogenase levels likely reflect reduced inflammation. These results confirm similar findings in adults and adolescents, and suggest that there is no need for routine laboratory monitoring of children aged 6-11 years treated with dupilumab + TCS for severe AD.Trial registrationClinicalTrials.gov Identifier: NCT03345914. Does treatment with dupilumab require routine laboratory monitoring in 6- to 11-year-old children with severe atopic dermatitis? (MP4 180482 kb).
| S-EPMC8418591 | biostudies-literature
Project description:BackgroundChildren with severe atopic dermatitis (AD) have a multidimensional disease burden.ObjectiveHere we assess the clinically meaningful improvements in AD signs, symptoms, and quality of life (QoL) in children aged 6-11 years with severe AD treated with dupilumab compared with placebo.MethodsR668-AD-1652 LIBERTY AD PEDS was a randomized, double-blinded, placebo-controlled, parallel-group, phase III clinical trial of dupilumab with concomitant topical corticosteroids (TCS) in children aged 6-11 years with severe AD. This post hoc analysis focuses on 304 patients receiving either dupilumab or placebo with TCS and assessed the percentage of patients considered responsive to dupilumab treatment at week 16.ResultsAt week 16, almost all patients receiving dupilumab + TCS (95%) demonstrated clinically meaningful improvements in AD signs, symptoms, or QoL compared with placebo + TCS (61%, p < 0.0001). Significant improvements were seen as early as week 2 and sustained through the end of the study in the full analysis set (FAS) and the subgroup of patients with an Investigator's Global Assessment score greater than 1 at week 16.LimitationsLimitations include the post hoc nature of the analysis and that some outcomes were not prespecified; the small number of patients in some subgroups potentially limits generalizability of findings.ConclusionTreatment with dupilumab provides significant and sustained improvements within 2 weeks in AD signs, symptoms, and QoL in almost all children with severe AD, including those who did not achieve clear or almost clear skin by week 16.Trial registrationNCT03345914. Video Abstract: Does dupilumab provide clinically meaningful responses in children 6 to 11 years old with severe atopic dermatitis? (MP4 99484 kb).
| S-EPMC10460374 | biostudies-literature
Project description:IntroductionTreatment options for children younger than 6 years with severe atopic dermatitis (AD) are limited, as systemic immunosuppressants may present safety concerns in this young age group. Dupilumab is the first systemic treatment option approved for infants and young children with severe AD in the European Union. This study reports the efficacy and safety of dupilumab with concomitant low-potency corticosteroids in children aged 6 months to 5 years with severe AD.MethodsThis was a pre-specified subgroup analysis of data for patients aged 6 months to 5 years with severe AD at baseline (Investigator's Global Assessment [IGA] = 4) from a randomised, double-blind, placebo-controlled, phase III trial of dupilumab. Patients were randomised to either subcutaneously administered dupilumab (200/300 mg) or matched placebo every 4 weeks, plus low-potency topical corticosteroids for 16 weeks. Co-primary endpoints at week 16 were the proportion of patients with IGA ≤ 1 (clear or almost clear skin) and the proportion of patients with ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Secondary endpoints at week 16 included mean changes in EASI, pruritus, skin pain, sleep loss and quality of life.ResultsThe analysis included 125 patients (63 receiving dupilumab vs. 62 placebo). At week 16, significantly more patients receiving dupilumab vs. placebo had achieved IGA ≤ 1 (14.3% vs. 1.6%; P = 0.0085) and EASI-75 (46.0% vs. 6.6%; P < 0.0001). Significant improvements with dupilumab were observed in all secondary endpoints, including a least squares mean 48.9% reduction in pruritus. The overall incidence of adverse events (AEs) was similar between the dupilumab and placebo groups (66.7% vs. 73.8%). No dupilumab-related AEs were serious or led to treatment discontinuation.ConclusionDupilumab significantly improved AD signs, symptoms and quality of life in children aged 6 months to 5 years with severe AD with acceptable safety.Trial registrationThe trial was registered with ClinicalTrials.gov with ID number NCT03346434, part B.
| S-EPMC10879230 | biostudies-literature
Project description:BackgroundRuxolitinib cream has demonstrated anti-inflammatory and antipruritic activity and was well tolerated in a phase 3 study in patients aged 2-11 years with mild to moderate atopic dermatitis (AD).ObjectiveThis study examined the safety, tolerability, pharmacokinetics, efficacy, and quality of life (QoL) with ruxolitinib cream under maximum-use conditions and with longer-term use.MethodsEligible patients were aged 2-11 years with moderate to severe AD [Investigator's Global Assessment (IGA) score 3-4], and ≥ 35% affected body surface area (BSA). Patients applied 1.5% ruxolitinib cream twice daily to all baseline-identified lesions during the 4-week maximum-use period, then to active lesions only up to week 52 (patients with ≤ 20% affected BSA from week 8). Safety was assessed by frequency and severity of adverse events. Pharmacokinetic parameters were assessed as secondary endpoints, and efficacy and QoL were exploratory endpoints.ResultsOverall, 29 patients (median age 5 years) were enrolled. Treatment-emergent adverse events were reported in 9/29 patients (31.0%); there were no adverse events of special interest (i.e., no serious infections, malignancies, major adverse cardiovascular events, or thromboses) during the study period. Mean steady-state plasma concentration during the maximum-use period was below the known half-maximal inhibitory concentration of Janus kinase-mediated myelosuppression in adults. Reductions in affected BSA and IGA observed at week 4 were sustained with as-needed use through 52 weeks. Improvements in patient-reported outcomes and QoL measures were consistent with efficacy results.ConclusionThese results support the safety of ruxolitinib cream in children (2-11 years) with AD, including those with extensive disease, and are consistent with previous efficacy findings.ClinicaltrialsGov identifierNCT05034822, first registered 30 August 2021.
| S-EPMC11850462 | biostudies-literature
Project description:BackgroundFor children aged 6-11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management.ObjectivesThis analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914).MethodsEnrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight < 60 or ≥ 60 kg, respectively) for patients who did not achieve an Investigator's Global Assessment (IGA) score of 0/1 (clear/almost clear skin) at week 16, or prior to week 16 as rescue treatment. Additional patients were uptitrated to a weight-tiered q2w regimen following a protocol amendment. Patients who maintained an IGA score of 0/1 continuously for a 12-week period after week 40 discontinued dupilumab. They were monitored for relapse and were reinitiated on dupilumab if required.ResultsData for 321 patients (mean age 8.6 years) were analyzed, 254 (79%) of whom had completed the scheduled 52-week visit at the database lock. Most treatment-emergent adverse events were mild/moderate. By week 52, 41% of patients achieved an IGA score of 0/1, and 97%, 82%, and 50%, respectively, had at least a 50%, 75%, and 90% improvement from the parent study baseline in Eczema Area and Severity Index (EASI). By week 52, 29% of patients in the overall population had clear/almost clear skin sustained for 12 weeks and had stopped medication; of these, 40% relapsed and were subsequently reinitiated on treatment, with a mean time to reinitiation of 13.5 (standard deviation 5.2) weeks. Following reinitiation of dupilumab, 41% of the patients with evaluable data at the time of database lock had regained an IGA 0/1 clinical response.ConclusionsConsistent with results seen in adults and adolescents, long-term treatment with dupilumab in children aged 6-11 years with severe AD showed an acceptable safety profile and incremental clinical benefit. A substantial proportion of children who stopped dupilumab treatment after achieving clear/almost clear skin subsequently experienced disease recurrence, and required reinitiation of dupilumab, suggesting that continuous treatment may be necessary for maintenance of clinical benefit.Trial registrationClinicalTrials.gov Identifier NCT02612454.
| S-EPMC10613196 | biostudies-literature
Project description:Dupilumab demonstrated efficacy with an acceptable safety profile in two randomized, double-blind, placebo-controlled, parallel-group, phase III trials in adolescents (12-17 years; LIBERTY AD ADOL) and children (6-11 years; LIBERTY AD PEDS) with atopic dermatitis (AD) treated for 16 weeks. Here, we present the pharmacokinetic profiles and exposure-response (E-R) relationships of dupilumab that guided the posology in these populations. A total of 251 adolescent patients with moderate-to-severe AD were randomized to subcutaneous dupilumab monotherapy every 2 weeks (q2w; 200 mg q2w, baseline weight < 60 kg; 300 mg q2w, ≥ 60 kg), dupilumab 300 mg every 4 weeks (q4w; non-weight tiered), or placebo; 367 children with severe AD were randomized to dupilumab q2w (100 mg q2w, baseline weight < 30 kg; 200 mg q2w, ≥ 30 kg), dupilumab 300 mg q4w, or placebo. Children received concomitant topical corticosteroids in addition to dupilumab, and loading doses were administered at the start of therapy. Mean dupilumab trough concentrations at week 16 for weight subcategories in each dosing regimen were compared with adult exposures for the approved dupilumab 300 mg q2w regimen. Positive E-R relationships were demonstrated between dupilumab trough concentrations and AD outcome measures across patient populations and regimens; no relationship was observed with treatment-emergent conjunctivitis. Based on these analyses, a weight-tiered posology was proposed for adolescents (200/300 mg q2w in patients 30-< 60 kg/≥ 60 kg) and children (300 mg q4w in patients 15-< 30 kg, 200 mg q2w in patients 30-< 60 kg) with moderate-to-severe AD.
| S-EPMC9290854 | biostudies-literature
Project description:We report 10 cases of conjunctivitis in atopic dermatitis (AD) patients treated with dupilumab from November 2017 to November 2018 in our institution, who were referred to the ophthalmology department for diagnosis and management of conjunctivitis. We also describe ocular surface findings in these patients before the first injection of dupilumab. During the first 6 months post initiation of dupilumab, incidence of conjunctivitis was 27% (5/18) in patients treated from November 2017 to April 2018 who had not had ocular examination previously. This rate dropped to 12% (3/25) after systematic ophthalmological referral before initiation of dupilumab. Patients who developed conjunctivitis had mean SCORAD score (Scoring Atopic Dermatitis) of 60.4 ± 20 (35-88) and mean EASI score (Eczema Area and Severity Index) of 37 ± 17 (14.6-56). Mean age was 36 years (20-51). Most patients had a long history of AD (> 10 years). Mean delay of ocular surface inflammation was 3.5 months, ranging from 1 to 8 months. One patient had to discontinue dupilumab because of severe follicular conjunctivitis. We observed two clinical patterns of ocular surface diseases: a mild non-specific conjunctivitis with dry eyes, which improved with warm compresses and artificial tears without any recurrence; and a severe dupilumab-induced follicular conjunctivitis without keratitis, which required specific ophthalmological management.
| S-EPMC6692787 | biostudies-literature
Project description:BackgroundDevelopment of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) to monoclonal antibodies may adversely impact pharmacokinetics, efficacy, and/or safety.ObjectiveTo describe incidence, titer, and persistence of dupilumab ADAs and NAbs, and their effects on pharmacokinetics, efficacy, and safety in patients with atopic dermatitis (AD).MethodsThis analysis included seven phase 3 randomized, placebo-controlled (N=2,992) and two long-term open-label extension (N=2,287) trials of subcutaneous dupilumab in adults and pediatric patients with moderate-to-severe AD. ADA, NAb, and dupilumab concentration in serum were assessed using validated immunoassays. ADA impacts on efficacy (EASI) and safety were assessed.ResultsTreatment-emergent ADAs were observed in up to 8.6% (aged ≥18 years), 16.0% (12-17 years), 5.3% (6-11 years), and 2.0% (6 months to 5 years) dupilumab-treated patients. Among dupilumab-treated patients, ≤3.7% had persistent responses, <1% had high titers (≥10,000), and ≤5.1% were NAb-positive. NAbs were more common in patients with moderate- and high-titer ADA responses. High-titer ADAs, while infrequent, were the variable most associated with lower dupilumab concentrations in serum and loss of efficacy, independent of NAb status. Efficacy was generally similar in ADA-positive and -negative patients. For most patients with high- or moderate-titer ADAs, titers decreased and efficacy improved over time with continued dupilumab treatment. ADA-positive and -negative patients had similar incidences of treatment-emergent and serious treatment-emergent adverse events. One patient with high-titer ADAs developed serum sickness.ConclusionIn patients with AD, ADAs and NAbs had minimal impact on dupilumab concentration, efficacy, and safety, except for high-titer ADAs in a small number of patients.Clinical trial registrationClinicalTrials.gov, identifiers (NCT02277743, NCT02277769, NCT02260986, NCT02395133, NCT01949311, NCT03054428, NCT03345914, NCT02612454, and NCT03346434).
| S-EPMC11586717 | biostudies-literature
Project description:BackgroundPatients with atopic dermatitis (AD), particularly infants and young children, are at greater risk of developing skin infections. In this study, we assessed infection rates in AD patients aged 6 months to 5 years treated with dupilumab.MethodsIn LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo, with concomitant low-potency topical corticosteroids, every 4 weeks for 16 weeks. Exposure-adjusted infection rates were used to compare treatment groups.ResultsThe analysis included 162 patients, of whom 83 received dupilumab and 79 received placebo. Total infection rates were not significantly different between the dupilumab and placebo groups (rate ratio [RR] 0.75, 95% CI 0.48-1.19; p = 0.223). Non-herpetic adjudicated skin infections and bacterial infections were significantly less frequent with dupilumab versus placebo (non-herpetic skin infections: RR 0.46, 95% CI 0.21-0.99; p = 0.047; bacterial infections: RR 0.09, 95% CI 0.01-0.67; p = 0.019), and the number of patients using systemic anti-infective medication was significantly lower in the dupilumab group (RR 0.52, 95% CI 0.30-0.89; p = 0.019). There were no significant differences in the number of herpetic infections between the dupilumab and placebo groups (RR 1.17, 95% CI 0.31-4.35; p = 0.817). The number of patients with two or more infection events was significantly higher in the placebo group (RR 0.29, 95% CI 0.12-0.68; p = 0.004), and no severe or serious infections (including eczema herpeticum) were observed among patients receiving dupilumab.ConclusionsThese data suggest that dupilumab treatment in infants and children younger than 6 years with AD does not increase overall risk of infections and is associated with a reduced risk of bacterial and non-herpetic skin infections compared with placebo, resulting in a reduced need for anti-infective medication.Trial registrationThe trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. INFOGRAPHIC.
| S-EPMC10890978 | biostudies-literature
Project description:We report the cases of two adolescent siblings with severe atopic dermatitis, who, despite weighing approximately 40kg, presented a good response to dupilumab with the off-label dose for individuals aged 12 years and weighing 60kg. Both had already used cyclosporine, azathioprine, methotrexate and oral corticosteroids for long periods, plus topical treatments with no adequate disease control. Skin lesions were constant and widespread, with frequent skin infections and very poor quality of life, with numerous physical and psychosocial consequences, such as dropping out of school activities due to severe itching, appearance and bullying. They also showed delayed growth and development. In 2018, dupilumab, an immunobiological agent, was approved for treatment of moderate to severe atopic dermatitis in adults and, in 2019, extended to the 12-17-year age group. Although it had already been approved by the Brazilian Health Surveillance Agency, the 200mg presentation (indicated for the weight of patients) was not available, with no expected arrival date. Therefore, weighing the risks and benefits of the situation of both, we chose to treat them with an adult dose (loading dose of 600mg subcutaneously, and 300mg subcutaneously every 2 weeks) despite the low weight. So far, they have received eight injections, showing significant improvement of disease and quality of life. There were no major adverse effects, only worsening of allergic conjunctivitis in one of them. The patients and their family are very satisfied, and we believe that the therapy has been successful.
| S-EPMC8081439 | biostudies-literature