Low-dose Avastin for ROP
Smaller dosages of bevacizumab as effective in ROP treatment
Retinopathy of prematurity (ROP) can be treated effectively with a fraction of the dose of bevacizumab used in the currently recommended regimen, greatly reducing systemic exposure and the dangers it may pose to infants’ development, according to the findings of a new study published in JAMA Ophthalmology.
“In the current study, we found that 0.004mg of bevacizumab – a dose that’s merely 0.6% of the dose used in the 2011 study of Avastin for ROP – may be the lower limit to be effective for most infants with ROP,” said the study’s protocol chair, David K. Wallace MD, MPH, Jaeb Centre, chair of ophthalmology at the Indiana University School of Medicine.
The masked, multi-centre, dose de-escalation study involved 59 preterm infants with type 1 ROP that underwent a single intravitreal injection of bevacizumab (Avastin®, Roche) at low dosages ranging from 0.008mg to 0.002mg between April 2017 and May 2019. The patients had a mean birth weight was 664 grams, and a mean gestational age of 24.8 weeks.
The patients were treated in consecutive groups that received progressively lower dosages of bevacizumab than the previous group.
Upon each dosage group’s completion of four weeks’ follow-up, an independent data safety and monitoring committee reviewed the outcomes to determine the bevacizumab dosage to use in the next treatment group.
Short-term success – defined as improvement in ROP within four days after the injection and no recurrence requiring treatment within four weeks – was achieved in 13 of 13 eyes (100%) receiving 0.016mg bevacizumab, nine of nine eyes (100%) receiving 0.008mg, nine (90%) of 10 eyes receiving 0.004mg but only 17 (74%) of 23 eyes receiving 0.002mg.
Previous research has shown that bevacizumab enters systemic circulation following intravitreal injection and decreases the plasma levels of vascular endothelial growth factors (VEGFs) the study’s authors said. That raises concerns about possible adverse effects, since VEGFs are essential for normal development of the brain, lungs, bones, kidneys, and retina.
The authors also note that the strength of the study’s finding was limited by the small number of patients it included and its short follow-up time. However, the researchers will continue in their follow-up of the infants in the study and report recurrences and two-year results.
The study was conducted by the Paediatric Eye Disease Investigator Group (PEDIG) and supported by the National Eye Institute (NEI), part of the National Institutes of Health.