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Record W4391167053 · doi:10.1007/s40272-023-00611-9

Infections in Children Aged 6 Months to 5 Years Treated with Dupilumab in a Placebo-Controlled Clinical Trial of Moderate-to-Severe Atopic Dermatitis

2024· article· en· W4391167053 on OpenAlex
Amy S. Paller, Elaine C. Siegfried, Michael J. Cork, Peter D. Arkwright, Lawrence F. Eichenfield, Michele Ramien, Faisal A. Khokhar, Zhen Chen, Annie Zhang, Sonya Cyr

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenuePediatric Drugs · 2024
Typearticle
Languageen
FieldMedicine
TopicDermatology and Skin Diseases
Canadian institutionsAlberta Children's HospitalUniversity of Calgary
FundersNational Institute for Health and Care ResearchRegeneron PharmaceuticalsSanofi
KeywordsPlaceboDupilumabMedicineAtopic dermatitisInternal medicineConcomitantEczema Area and Severity IndexRandomized controlled trialPlacebo-controlled studyDermatologyGastroenterologyDouble blindPathology

Abstract

fetched live from OpenAlex

Patients 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. In 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. The 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. These 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. The trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. Patients with atopic dermatitis (AD), a chronic disease of the skin, are at greater risk of developing skin infections, particularly infants and young children. Several medications for AD may weaken the patient’s immune system, further increasing the risk of infections. Dupilumab is a recently developed drug for AD that should not interfere with the patient’s immune defenses against bacterial, viral, or fungal infections. In this study, we evaluated the effect of dupilumab on infections in children aged 6 months to 5 years with moderate-to-severe AD. Patients received 200 or 300 mg of dupilumab (depending on the child’s weight) or placebo, together with ointments containing mild steroids, every 4 weeks for 16 weeks. At the end of treatment, total infections were not significantly different between patients receiving dupilumab and placebo. Furthermore, patients receiving dupilumab experienced significantly less bacterial and non-herpetic skin infections and used significantly less anti-infective medication compared with patients receiving placebo. Herpetic infections were also not significantly different between dupilumab- and placebo-treated patients. Finally, significantly more patients in the placebo group experienced two or more infections. This study demonstrates that dupilumab does not increase the risk of infections in infants and young children with AD and can decrease the use of anti-infective medication.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.125
Threshold uncertainty score0.547

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.289
Teacher spread0.279 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it