Evidence map›Paper›PMID 32855889›Full record

ArticleTranslational vision science & technology2020

Ranibizumab Population Pharmacokinetics and Free VEGF Pharmacodynamics in Preterm Infants With Retinopathy of Prematurity in the RAINBOW Trial.

Matthew Fidler, Brian W Fleck, Andreas Stahl, Neil Marlow, James E Chastain, Jun Li, Domenico Lepore, James D Reynolds, Michael F Chiang, Alistair R Fielder and 1 more

Open access · goldAbstract read
In one paragraph

Article in Translational vision science & technology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Mathematical Models of Ocular Drug Delivery.Investigative ophthalmology & visual science · 2024
    Review
  9. Article
  10. Review
  11. Review
  12. Pathophysiology of Retinopathy of Prematurity.Annual review of vision science · 2023
    Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 9 institutions in 5 countries.

Matthew FidlerPharmacometrics Ophthalmology, Novartis Pharmaceuticals Corporation, Fort Worth, TX, USA.
Brian W FleckDepartment of Ophthalmology, Princess Alexandra Eye Pavilion, Edinburgh, UK.
Andreas StahlDepartment of Ophthalmology, University Medical Center, Greifswald, Germany.
Neil MarlowAcademic Neonatology, UCL Elizabeth Garrett Anderson Institute for Women's Health, London, UK.
James E ChastainNovartis Institutes for BioMedical Research, Inc., Cambridge, MA, USA.
Jun LiNovartis Pharma, Basel, Switzerland.
Domenico LeporeDepartment of Ophthalmology, Gemelli Foundation IRCSS, Catholic University of the Sacred Heart, Rome, Italy.
James D ReynoldsRoss Eye Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
Michael F ChiangCasey Eye Institute, Oregon Health & Science University, Portland, OR, USA.
Alistair R FielderDepartment of Optometry and Visual Science, City, University of London, London, UK.
RAINBOW study group†
City, University of London · GBJacobs Institute · USNovartis (Switzerland) · CHNovartis (United States) · USOregon Health & Science University · USPrincess Alexandra Eye Pavilion · GBUniversità Cattolica del Sacro Cuore · ITUniversitätsmedizin Greifswald · DEUniversity College Hospital · GB

Funding

Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
NEI NIH HHS P30 EY010572
6 · The paper itself

Abstract

Purpose: To develop a population pharmacokinetic (PK) model for intravitreal ranibizumab in infants with retinopathy of prematurity (ROP) and assess plasma free vascular endothelial growth factor (VEGF) pharmacodynamics (PD). Methods: The RAnibizumab compared with laser therapy for the treatment of INfants BOrn prematurely With retinopathy of prematurity (RAINBOW) trial enrolled 225 infants to receive a bilateral intravitreal injection of ranibizumab 0.1 mg, ranibizumab 0.2 mg, or laser in a 1:1:1 ratio and included sparse sampling of blood for population PK and PD analysis. An adult PK model using infant body weight as a fixed allometric covariate was re-estimated using the ranibizumab concentrations in the preterm population. Different variability, assumptions, and covariate relationships were explored. Model-based individual predicted concentrations of ranibizumab were plotted against observed free VEGF concentrations. Results: Elimination of ranibizumab had a median half-life of 5.6 days from the eye and 0.3 days from serum, resulting in an apparent serum half-life of 5.6 days. Time to reach maximum concentration was rapid (median: 1.3 days). Maximum concentration (median 24.3 ng/mL with ranibizumab 0.2 mg) was higher than that reported in adults. No differences in plasma free VEGF concentrations were apparent between the groups or over time. Plotted individual predicted concentrations of ranibizumab against observed free VEGF concentrations showed no relationship. Conclusions: In preterm infants with ROP, elimination of ranibizumab from the eye was the rate-limiting step and was faster compared with adults. No reduction in plasma free VEGF was observed. The five-year clinical safety follow-up from RAINBOW is ongoing. Translational Relevance: Our population PK and VEGF PD findings suggest a favorable ocular efficacy: systemic safety profile for ranibizumab in preterm infants.

Indexed as

RanibizumabRetinopathy of PrematurityAngiogenesis InhibitorsHumansInfantInfant, NewbornInfant, PrematureVascular Endothelial Growth Factor AAngiogenesis InhibitorsRanibizumabVascular Endothelial Growth Factor ApharmacokineticsranibizumabROPVEGF

Identifiers

PMID32855889
PMCPMC7422765
OpenAlexW3045720070

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.