Ranibizumab for Diabetic Macular Edema: Results from 2 Phase III Randomized Trials: RISE and RIDE

Elsevier, Ophthalmology, Volume 119, Issue 4, April 2012, Pages 789-801
Authors: 
Quan Dong Nguyen, David M. Brown, Dennis M. Marcus, David S. Boyer, Sunil Patel, Leonard Feiner, Andrea Gibson, Judy Sy, Amy Chen Rundle, J. Jill Hopkins, Roman G. Rubio, Jason S.Ehrlich, RISE and RIDE Research Group

Purpose

To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients.

Design

Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection–controlled, randomized studies.

Participants

Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40–20/320 Snellen equivalent) and central subfield thickness ≥275 μm on time-domain optical coherence tomography (OCT).

Intervention

Monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol–specified criteria.

Main Outcome Measures

Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months.

Results

In RISE (NCT00473330), 377 patients were randomized (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained ≥15 letters versus 44.8% of 0.3-mg (P<0.0001; difference vs sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8–34.8) and 39.2% of 0.5-mg ranibizumab patients (P<0.001; adjusted difference, 20.9%; 95% CI, 10.7–31.1). In RIDE (NCT00473382), 382 patients were randomized (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). Significantly more ranibizumab-treated patients gained ≥15 letters: 12.3% of sham patients versus 33.6% of 0.3-mg patients (P<0.0001; adjusted difference, 20.8%; 95% CI, 11.4–30.2) and 45.7% of 0.5-mg ranibizumab patients (P<0.0001; adjusted difference, 33.3%; 95% CI, 23.8–42.8). Significant improvements in macular edema were noted on OCT, and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients. Ranibizumab-treated patients underwent significantly fewer macular laser procedures (mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3–0.8 in ranibizumab groups). Ocular safety was consistent with prior ranibizumab studies; endophthalmitis occurred in 4 ranibizumab patients. The total incidence of deaths from vascular or unknown causes, nonfatal myocardial infarctions, and nonfatal cerebrovascular accidents, which are possible effects from systemic vascular endothelial growth factor inhibition, was 4.9% to 5.5% of sham patients and 2.4% to 8.8% of ranibizumab patients.

Conclusions

Ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular edema in patients with DME, with low rates of ocular and nonocular harm.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.