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Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants.

Publication ,  Journal Article
Writing Committee for the Pediatric Eye Disease Investigator Group, ; Hartnett, ME; Wallace, DK; Dean, TW; Li, Z; Boente, CS; Dosunmu, EO; Kong, L ...
Published in: JAMA Ophthalmol
April 1, 2022

IMPORTANCE: Intravitreal bevacizumab effectively treats severe retinopathy of prematurity (ROP), but it enters the bloodstream and may reduce serum vascular endothelial growth factor (VEGF), potentially causing detrimental effects on developing organs in the premature infant. OBJECTIVE: To evaluate the association of intravitreal bevacizumab with plasma bevacizumab and VEGF concentrations at 2 and 4 weeks after predefined, de-escalating doses of intravitreal bevacizumab were administered to infants with severe ROP. DESIGN, SETTING, AND PARTICIPANTS: This phase 1 dose de-escalation case series study was conducted at 10 US hospitals of ophthalmology institutions from May 21, 2015, to May 7, 2019. Blood samples were collected 2 and 4 weeks after intravitreal bevacizumab injection. Participants included 83 premature infants with type 1 ROP in 1 or both eyes and no previous ROP treatment. Data were analyzed from April 2017 to August 2021. INTERVENTIONS: Study eyes received a single bevacizumab injection of 0.250 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. When the fellow eye required treatment, one dose higher was administered. Total dose administered at baseline was defined as the sum of doses given to each eye within 3 days of initial study-eye injection. MAIN OUTCOMES AND MEASURES: Plasma bevacizumab concentration at 2 and 4 weeks after injection and the percentage change in plasma VEGF concentrations from pretreatment levels. RESULTS: A total of 83 infants (mean [SD] age, 25 [2] weeks; 48 boys [58%]) were included in this study. Higher doses of bevacizumab administered at baseline were associated with higher plasma bevacizumab concentrations at 2 weeks (ρ, 0.53; 95% CI, 0.31-0.70) and 4 weeks (ρ, 0.44; 95% CI, 0.18-0.64). Plasma VEGF concentrations decreased by 50% or more from pretreatment levels in 40 of 66 infants (61%) at 2 weeks and 31 of 61 infants (51%) at 4 weeks, but no association was observed between the total dose of bevacizumab administered at baseline and percentage change in plasma VEGF concentrations 2 weeks (ρ, -0.04; 95% CI, -0.28 to 0.20) or 4 weeks (ρ, -0.17; 95% CI, -0.41 to 0.08) after injection. CONCLUSIONS AND RELEVANCE: Results of this phase 1 dose de-escalation case series study revealed that bevacizumab doses as low as 0.002 mg were associated with reduced plasma VEGF levels for most infants at 2 and 4 weeks after intravitreal administration; however, no association was observed between total bevacizumab dose administered and reductions in plasma VEGF levels from preinjection to 2 weeks or 4 weeks. Additional studies are needed to evaluate the long-term effects of low-dose bevacizumab on neurodevelopment and retinal structure.

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Published In

JAMA Ophthalmol

DOI

EISSN

2168-6173

Publication Date

April 1, 2022

Volume

140

Issue

4

Start / End Page

337 / 344

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Retinopathy of Prematurity
  • Male
  • Intravitreal Injections
  • Infant, Newborn
  • Infant
  • Humans
  • Gestational Age
  • Female
  • Bevacizumab
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Writing Committee for the Pediatric Eye Disease Investigator Group, ., Hartnett, M. E., Wallace, D. K., Dean, T. W., Li, Z., Boente, C. S., … Holmes, J. M. (2022). Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants. JAMA Ophthalmol, 140(4), 337–344. https://doi.org/10.1001/jamaophthalmol.2022.0030
Writing Committee for the Pediatric Eye Disease Investigator Group, Jonathan M., M Elizabeth Hartnett, David K. Wallace, Trevano W. Dean, Zhuokai Li, Charline S. Boente, Eniolami O. Dosunmu, et al. “Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants.JAMA Ophthalmol 140, no. 4 (April 1, 2022): 337–44. https://doi.org/10.1001/jamaophthalmol.2022.0030.
Writing Committee for the Pediatric Eye Disease Investigator Group, Hartnett ME, Wallace DK, Dean TW, Li Z, Boente CS, et al. Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants. JAMA Ophthalmol. 2022 Apr 1;140(4):337–44.
Writing Committee for the Pediatric Eye Disease Investigator Group, Jonathan M., et al. “Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants.JAMA Ophthalmol, vol. 140, no. 4, Apr. 2022, pp. 337–44. Pubmed, doi:10.1001/jamaophthalmol.2022.0030.
Writing Committee for the Pediatric Eye Disease Investigator Group, Hartnett ME, Wallace DK, Dean TW, Li Z, Boente CS, Dosunmu EO, Freedman SF, Golden RP, Kong L, Prakalapakorn SG, Repka MX, Smith LE, Wang H, Kraker RT, Cotter SA, Holmes JM. Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants. JAMA Ophthalmol. 2022 Apr 1;140(4):337–344.

Published In

JAMA Ophthalmol

DOI

EISSN

2168-6173

Publication Date

April 1, 2022

Volume

140

Issue

4

Start / End Page

337 / 344

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Retinopathy of Prematurity
  • Male
  • Intravitreal Injections
  • Infant, Newborn
  • Infant
  • Humans
  • Gestational Age
  • Female
  • Bevacizumab