Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema

Abstract

Purpose Provide 2-year efficacy, safety and treatment results comparing three anti-vascular endothelial growth factor (anti-VEGF) agents for center-involved diabetic macular edema (DME) utilizing a standardized follow-up and retreatment regimen. Design Randomized clinical trial. Participants 660 participants with DME causing visual acuity (VA) impairment. Methods Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed as frequently as monthly utilizing a protocol-specific follow-up and retreatment regimen. Focal/grid laser was added if DME persisted and was not improving at 6 months or later. Visits occurred every 4 weeks during year 1, and were extended up to every 4 months thereafter when VA and macular thickness were stable and injections were deferred. Main Outcome Measures Change in VA (efficacy), ocular/systemic adverse events (safety), retreatment frequency. Results Median numbers of injections in year 2 were 5, 6, 6 and over 2 years were 15, 16, 15 in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P=0.08). Focal/grid laser was administered in 41%, 64%, and 52%, respectively (aflibercept-bevacizumab: P<0.001, aflibercept-ranibizumab: P=0.04, bevacizumab-ranibizumab: P=0.01). From baseline to 2 years, mean VA letter score improved by 12.8 with aflibercept, 10.0 with bevacizumab, and 12.3 with ranibizumab. Treatment group differences varied by baseline VA (interaction P=0.02). With worse baseline VA (20/50-20/320), mean improvement was 18.3, 13.3, and 16.1 letters, respectively (aflibercept-bevacizumab: P=0.02, aflibercept-ranibizumab: P=0.18, ranibizumab-bevacizumab: P=0.18). With baseline VA 20/32-20/40, mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P>0.10 for pairwise comparisons). Anti-Platelet Trialists’ Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P=0.047: aflibercept-bevacizumab: P=0.34, aflibercept-ranibizumab: P=0.047, ranibizumab-bevacizumab: P=0.20; global P=0.09 adjusted for potential confounders). Conclusion All 3 anti-VEGF groups had visual acuity improvement at 2 years with a decreased number of injections in year 2. VA outcomes were similar among treatment groups for eyes with baseline VA 20/32-20/40. Among eyes with worse baseline VA, aflibercept, on average, had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials.

South Asian diabetic macular oedema treated with ranibizumab (ADMOR)—real-life experience

“…2,3,4,13 It was reported that studies with fixed dosing 4,5 had better visual outcomes than studies with prn or extended treatment intervals. 2,13 However, the recent DRCRNet protocol T study 6 has reported very good results with as Results for other studies are also shown for 6, 12, and 24 months as stated. a Data from 68 weeks.…”

“…1 Several multi-centre randomised trials have demonstrated the efficacy of ranibizumab for DMO. [2][3][4][5][6] Ranibizumab has been introduced as a treatment option within the NHS, for DMO where central retinal thickness exceeds 400 μm (http://guidance.nice.org.uk/TA274/ Guidance/pdf/English).…”

Update on the Management of Diabetic Macular Edema

“…[12][13][14][15][16][17][18] Although a detailed review of the many anti-VEGF studies is beyond the scope of this article, the Diabetic Retinopathy Clinical…”

Aflibercept in diabetic macular edema: evaluating efficacy as a primary and secondary therapeutic option

“…In addition, different patients respond differently to aflibercept, some requiring as little as four to five injections in the first year and a bimonthly fixed dosing regimen would also over treat the early and good responders. 15 Finally, bimonthly dosing can not be maintained indefinetly and it is expected that after 2 years of therapy patients will be shifted to PRN.…”

“…Therefore at least for bevacizumab treated patients, early switching might be worth exploring if the primary aim is achieving better anatomic outcomes. 15,56 …”