Six-month findings from the SCORE2 randomized clinical trial have shown bevacizumab is noninferior to aflibercept for treatment of central retinal vein occlusion (CRVO).
“This head-to-head comparison of two widely used drugs for treatment of macular edema due to central retinal vein occlusion shows that both are effective in improving vision,” said Ingrid U. Scott, MD, MPH, professor of ophthalmology and public health sciences at Penn State University, and chair of the study. “The bottom line is that in patients with CRVO-associated macular edema, Avastin was as effective as Eylea in terms of visual acuity after six months of treatment.”
Study design
The Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) trial was conducted at 66 centers across the United States, and included 362 patients with macular edema due to CRVO or hemiretinal vein occlusion (HRVO). Eyes were randomized 1:1 to receive bevacizumab (1.25 mg; n = 182) or aflibercept (2.0 mg; n = 180) every 4 weeks through month 6. Patients with HRVO represented roughly 15% of the participants in each arm; this inclusion was aimed to enhance generalizability.
Outcomes
With a noninferiority margin of 5 letters in visual acuity letter score (VALS), bevacizumab was found to be noninferior to aflibercept after 6 monthly injections. On average, visual acuity improved from 20/100 to 20/40 in both groups. Anatomy (central subfield thickness (CST) on SD-OCT) was not a primary outcome measure, but bevacizumab was associated with a significant lower proportion of eyes that achieved resolution of macular edema compared to aflibercept (29% vs. 54%)
The rates of adverse events, such as elevated IOP, were low and similar in both groups. One participant in the bevacizumab group had endophthalmitis (culture negative).
Other considerations
The 2 treatment groups were balanced except for the shorter time between diagnosis of macular edema and randomization in the bevacizumab group. As earlier treatment could certainly influence the outcome, a secondary noninferiority analysis was run to analyze the extent to which this could confound the primary results. The authors reported that the adjusted secondary analysis reached the same noninferiority conclusion.
Caution should be taken in extrapolating the result of this short-term clinical trial analysis to clinical practice. Adherence to the fixed-dosing schedule was very high in this trial, whereas compliance is not as high in clinical practice, even with variable dosing regimens such as treat-and-extend.
SCORE2 in context
It's important to note that the participants were equivalent in number when stratified by VA letter score (good, moderate, poor), between each arm. Unlike Protocol T of DRCR.net, which showed a differential in treatment effect on VALS in the poor VA stratum (advantage of aflibercept over bevacizumab among eyes with worse baseline VA at 1 year, an effect that persisted at 2 years), in SCORE2 no such differences were identified in association with baseline VA stratum.
In contrast to COPERNICUS and GALILEO which enrolled only treatment-naive eyes, SCORE2 allowed eyes that had prior treatment with anti-VEGF (with 2-month washout period) or steroid (4-month washout period). Overall, more than 1/3 of patients in each arm were previously treated with either anti-VEGF or steroid. However, SCORE2 did not find any significant differences between treatment-naive and previously-treated eyes.
Study limitations
- Time: Six months is a relatively short follow-up. It also does not match up with the timing of primary outcome assessment in Protocol T, so any comparisons are inherently limited. Since CRVO-associated macular edema is a chronic condition requiring indefinite treatment, the implied economic savings should be revisited as the study continues.
- Anatomy: The study doesn’t answer how the VALS might be impacted with longer follow-up, given the significant difference between bevacizumab and aflibercept to reduce macular edema. The authors note that in this current trial the difference in anatomic response did not translate into poorer VA outcomes, and they point out that this was also true in CATT and at 12 months in participants with better baseline VA in Protocol T. However, RVO is different from AMD or DME, and the cumulative effect of unresolved fluid on VA remains unclear.
- Dosing: SCORE2 reports results at 6 months after fixed monthly treatment. Adherence to the study protocol was high with approximately 90% of participants receiving all 6 monthly injections. After 6 months, some patients will be assigned to a treat-and-extend regimen. Future results will show whether differences arise in participants assigned to treatment groups that are not defined by a fixed-dosing schedule.
- Ranibizumab: Although some assumptions may be made from other trials (e.g., CATT), SCORE2 does not offer direct conclusions regarding ranibizumab.