Could ranibizumab be more effective for ROP than laser therapy?

Findings from a recent study published in The Lancet’s eClinical Medicine evaluating the use of intravitreal ranibizumab vs laser therapy for treating retinopathy of prematurity (ROP) may point to a potentially groundbreaking new standard of care.

Let’s begin with some background.

While laser therapy has historically been considered a standard of care for ROP, the use of vascular endothelial growth factor (VEGF) inhibitors has also risen as a potential alternative treatment (thanks to findings from the 2011 Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity [BEAT-ROP] trial).

However, investigators of the BEAT-ROP trial noted clinical concerns for the long-term safety of these injections in infants with ROP, citing that “there are relatively few data on infant outcomes from controlled trials and no data describing outcomes into school age.”

Why would this be important?

Such concern has centered around the potential for suppression of systemic VEGF levels following intravitreal treatment may lead to potential long-term implications to somatic (ie: relating to the body) or neurological development.

Even further: There is currently limited data demonstrating longitudinal safety following anti-VEGF therapy.

Which brings us to this new research?

Indeed! These study authors sought to investigate an extension trial of RAnibizumab compared to laser therapy for the treatment of  INfants BOrn prematurely with retinopathy of prematurity (RAINBOW) (NCT02375971).

Here’s a quick refresher:

• The design: open-label multicenter, three-arm, randomized control trial (RCT) to determine  the potential superiority of intravitreal ranibizumab vs. laser ablation therapy
• The participants: very low birth weight infants (less than 1,500 g)
  • Criteria: diagnosed with bilateral ROP (n = 201)
• The dosages for evaluation (1:1:1):
  • Single bilateral intravitreal injection of ranibizumab 0.2 mg (n = 66)
  • Single bilateral intravitreal injection of ranibizumab 0.1 mg (n = 71)
  • Yttrium aluminum garnet (YAG) laser therapy (n = 64)
• Outcomes (measured at Week 24):
  • Primary: absence of active ROP and unfavorable structural outcomes in both eyes
  • Secondary: See here
• The study duration: 2 years

And the results?

The study authors reported that ranibizumab 0.2 mg may be superior to laser therapy, as it resulted in “fewer unfavorable ocular outcomes than laser therapy,“ along with an “acceptable 24-week safety profile.”

Alrighty, I’m up to date. Talk about this extension trial.

The 5-year RAINBOW extension trial enrolled 180 of the 201 eligible participants from the original study, broken down into:

• Ranibizumab 0.2 mg (n = 54)
• Ranibizumab 0.1 mg (n = 55)
• Laser therapy (n = 47)

The outcome measures:

• Primary: visual acuity (VA) in the better-seeing eye at age 5
• Secondary: results of a 5-year ophthalmic assessment, including:
  • Refractive error
  • Vision-related quality of life (QoL)
  • Non-ocular outcomes

Note: This study was the first to assess VA following anti-VEGF treatment.

And these findings?

Out of the 180 infants originally enrolled, 156 (87%) of 5-year-olds underwent 5-year evaluations.

Further, a total of 124 participants completed the visual acuity assessment, with the least square mean (95% Confidence interval [CI]) letter score in the better-seeing eye similar in all three trial arms:

• Following ranibizumab 0.2 mg: 66.8 (62.9 - 70.7)
• Following ranibizumab 0.1 mg: 64.6 (60.6 - 68.5)
• Following laser therapy: 62.1 (57.8 - 66.4)

Any ocular manifestations?

Yes, in fact. High myopia was observed in at least one eye of the following patients:

• Following ranibizumab 0.2 mg: 8% (4/52)
• Following ranibizumab 0.1 mg: 15% (8/55)
• Following laser therapy: 24% (11/45)

Any adverse effects?

Ocular and systemic secondary outcomes along with adverse events (AEs) were noted to be distributed similarly across all three treatment groups.

Further, there were no AEs observed for visual function or non-ocular outcomes that included:

• Neurodevelopment
• Gross motor function
• Growth
• Blood pressure
• Respiratory function

And the overall conclusions?

The study authors concluded that the 5-year data confirmed the original RAINBOW trial’s findings of VA being at least relatively equivocal to those treated with laser therapy in 5-year-old ROP patients following ranibizumab 0.2 mg treatment.

Lastly, the data also identified a lower risk for high myopia at the 5-year point—with no clinician concern for any long-term safety risks.