Clinical Studies:
DRCR.NET PROTOCOL T-2 YEAR
Citation: Wells JA, Glassman AR, Ayala AR, et al. Two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology 2016; 123: 1351-1359.
Key Points
- DRCR.net Protocol T is a randomized, controlled clinical trial that compared aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME)
- From months 0 through 6, eyes were treated at baseline and then monthly thereafter unless criteria to hold treatment were met. From months 6 – 12, eyes were evaluated monthly and treated unless there had been no improvement nor worsening in vision and imaging in response to the past 2 injections, and treatment was re-initiated if there was worsening. From months 12 through 24, eyes were evaluated and treated q4-16 weeks based on protocol criteria.
- At 2 years, there was no difference between aflibercept, ranibizumab, and bevacizumab for DME in eyes with baseline vision 20/32-20/40 (similar to one year results). In eyes with baseline vision worse than 20/50, visual outcomes at 2 years were better for aflibercept relative to bevacizumab (similar to one-year results), but there was no significant difference in visual outcomes for aflibercept versus ranibizumab.
- At 2 years, APTC rates were higher for ranibizumab (12%) as compared to aflibercept (5%) or bevacizumab (8%)
-
Objective
To compare outcomes for aflibercept versus bevacizumab versus ranibizumab for diabetic macular edema
-
STUDY DESIGN
Multicenter, randomized, controlled clinical trial
-
DURATION
24 Months
STUDY SUBJECTS
- DM1/DM2 with center-involving DME
- no anti-VEGF therapy in the preceding 12 months
Major inclusion criteria:
STUDY INTERVENTIONS
- aflibercept 2mg
- ranibizumab 0.3mg
- bevacizumab 1.25mg
(if the non-study eye needed treatment during the study period, the same medication was used)
Treatment schedule
- Injection at baseline
Then:
- From month 0 through week 24 (month 6), monthly evaluation and treatment q4w unless all 3 criteria below met
- VA ≥20/20
- CRT below eligibility threshold
- No improvement nor worsening in response to the past 2 injections
- (improvement = increase in VA of ≥ 5 letters or CRT decrease by ≥ 10%; worsening = decrease in VA of ≥ 5 letters or CRT increase by ≥ 10%)
- From week 24 (month 6) through 12 months, monthly evaluation and treatment unless no improvement nor worsening in response to the past 2 injections (improvement = increase in VA of ≥ 5 letters or CRT decrease by ≥ 10%; worsening = decrease in VA of ≥ 5 letters or CRT increase by ≥ 10%). Treatment re-initiated if VA or CRT worsened, however.
- From 12 months through 24 months (2nd year), evaluation every 4-16 weeks
Laser (focal, grid, or both) performed at or after 24 months based on protocol-defined criteria. Other treatment for DME allowed if the study eye met criteria for treatment failure.
VA/OCT technicians were masked; study coordinators/investigators were not masked; participants masked until 1-year results were published, and at that point, the participant could be switched therapies per investigator/protocol chair decision
RESULTS
Study population
- 660 participants
- Study completion 85-90%, similar in all groups
Treatment
- Median number of injections 15-16 over 2 years (similar in all 3 groups)
- Fewer aflibercept eyes (41%) underwent at least 1 macular laser session than bevacizumab (64%) or ranibizumab (52%)
Visual acuity end-points
- Overall, mean VA improvement was better for aflibercept (+12.8 letters) than for bevacizumab (+10). There was no statistically significant difference between aflibercept and ranibizumab (+12.3), nor bevacizumab and ranibizumab
- For VA 20/32 – 20/40, mean VA improvement was similar in all groups
- For VA ≤20/50, mean VA improvement was better for aflibercept (+18.1 letters) than bevacizumab (+13.3). There was no statistically significant difference between aflibercept and ranibizumab (+16.1), nor ranibizumab and bevacizumab
Anatomic outcomes
- Overall, reduction in CST: aflibercept > bevacizumab and ranibizumab > bevacizumab. No significant difference between aflibercept and ranibizumab
- Similar anatomic outcomes were found when looking at those with VA 20/32-20/40 and those with VA ≤20/50
Systemic adverse events
- APTC rates were aflibercept 5%, bevacizumab 8%, and ranibizumab 12% (statistically significant higher rates for ranibizumab vs. aflibercept or bevacizumab)
CONCLUSIONS
- There was no difference between aflibercept, ranibizumab, and bevacizumab for DME in eyes with baseline vision 20/32-20/40 at two years (similar to one-year results), but better visual outcomes at one year for aflibercept relative to bevacizumab (similar to one-year results) in eyes with baseline vision ≤20/50. The superior visual outcomes of aflibercept relative to ranibizumab at one year in eyes with vision ≤20/50 were not maintained in the second year.