Systemic exposure to aflibercept after intravitreal injection in premature neonates with retinopathy of prematurity: results from the FIREFLEYE randomized phase 3 study.
Eye (Lond)
; 38(8): 1444-1453, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38200320
ABSTRACT
BACKGROUND:
There are no data on pharmacokinetics, pharmacodynamics, and immunogenicity of intravitreal aflibercept in preterm infants with retinopathy of prematurity (ROP). FIREFLEYE compared aflibercept 0.4 mg/eye and laser photocoagulation in infants with acute-phase ROP requiring treatment.METHODS:
Infants (gestational age ≤32 weeks or birthweight ≤1500 g) with treatment-requiring ROP in ≥1 eye were randomized 21 to receive aflibercept 0.4 mg or laser photocoagulation at baseline in this 24-week, randomized, open-label, noninferiority, phase 3 study. Endpoints include concentrations of free and adjusted bound aflibercept in plasma, pharmacokinetic/pharmacodynamic exploration of systemic anti-vascular endothelial growth factor effects, and immunogenicity.RESULTS:
Of 113 treated infants, 75 received aflibercept 0.4 mg per eye at baseline (mean chronological age 10.4 weeks), mostly bilaterally (71 infants), and with 1 injection/eye (120/146 eyes). Concentrations of free aflibercept were highly variable, with maximum concentration at day 1, declining thereafter. Plasma concentrations of adjusted bound (pharmacologically inactive) aflibercept increased from day 1 to week 4, decreasing up to week 24. Six infants experienced treatment-emergent serious adverse events within 30 days of treatment; aflibercept concentrations were within the range observed in other infants. There was no pattern between free and adjusted bound aflibercept concentrations and blood pressure changes up to week 4. A low-titer (130), non-neutralizing, treatment-emergent anti-drug antibody response was reported in 1 infant, though was not clinically relevant.CONCLUSIONS:
24-week data suggest intravitreal aflibercept for treatment of acute-phase ROP is not associated with clinically relevant effects on blood pressure, further systemic adverse events, or immunogenicity. GOV IDENTIFIER NCT04004208.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes de Fusão
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Retinopatia da Prematuridade
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Recém-Nascido Prematuro
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Idade Gestacional
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Inibidores da Angiogênese
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Receptores de Fatores de Crescimento do Endotélio Vascular
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Fator A de Crescimento do Endotélio Vascular
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Injeções Intravítreas
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Female
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Humans
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Male
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Newborn
Idioma:
En
Revista:
Eye (Lond)
Assunto da revista:
OFTALMOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha