Elsevier

Ophthalmology

Volume 119, Issue 4, April 2012, Pages 789-801
Ophthalmology

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

Presented at: the 34th Annual Macula Society Meeting, March 9–12, 2011, Boca Raton, Florida; The Annual Meeting of the Association for Research in Vision and Ophthalmology, May 1–5, 2011, Fort Lauderdale, Florida; The 11th EURETINA Meeting, May 26–29, 2011, London, England; The American Diabetes Association's 71st Scientific Sessions, June 24–28, 2011, San Diego, California; Annual Meeting of the American Society of Retina Specialists, August 20–24, 2011, Boston, Massachusetts; and the 115th Annual Meeting of the American Academy of Ophthalmology, October 22–25, 2011, Orlando, Florida.
https://doi.org/10.1016/j.ophtha.2011.12.039Get rights and content

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.

Cited by (0)

*Group members listed online (http://aaojournal.org).

Manuscript no. 2011-1287.

Quan Dong Nguyen and David M. Brown contributed equally to this work.

Financial Disclosure(s): The authors have made the following disclosures:

Quan Dong Nguyen – Grants to investigator's institution – Genentech, Inc., Regeneron, Pfizer; Consulting fee or honorarium – Santen Pharmaceutical Co. Ltd., Bausch & Lomb; Board membership – Genentech, Inc.; Consultancy – Santen Pharmaceutical Co. Ltd., Bausch & Lomb.

David M. Brown – Grants to investigator's institution – Genentech, Inc., Regeneron, Novartis, Alcon, Allergan, Alimera, Eli Lilly, Molecular Partners, Ophthotech, Abbott, Schering Plough, Othera Pharmaceuticals, Paloma Pharmaceuticals, Neurotech, TargeGen, Sirion Therapeutics, Inc., Jerini AG; Consulting fee or honorarium – Genentech, Inc; Support for travel to meetings – Genentech, Inc.; Consultant – Genentech, Inc., Regeneron, Allergan, Alcon, Molecular Partners, Novartis, Oraya Therapeutics, Paloma Pharmaceuticals, Steba Biotech; Speakers bureau – Genentech, Inc.

Dennis M. Marcus – Grants to investigator's institution – Allergan, Eli Lilly, Genentech, Inc., Neovista, Pfizer, Regeneron, ThromboGenics; Steering committee member – Genentech, Inc., Regeneron; Advisory board – Genentech, Inc., Regeneron; Consultant – Genentech, Inc.

David S. Boyer – Consultant – Alcon, Allergan, Eyetech, Genentech, Inc., Novartis/QLT, Neurotech, Pfizer, Regeneron; Speakers bureau – Alcon, Allergan, Genentech, Inc., Pfizer; Clinical research projects – Alcon, Allergan, Genentech, Inc., Pfizer, Regeneron.

Sunil Patel – Grants to investigator's institution – Alcon, Allergan, Alimera, Genentech, Inc., Pfizer, Ophthotech, Regeneron; Consulting fee and fees for participation in review activities or honorarium – Genentech, Inc.; Consultant – Allergan, Ophthotech; Speakers bureau – Alcon; Stock/stock options – Ophthotech.

Leonard Feiner – Consultant – Genentech, Inc.; Speakers bureau – Genentech, Inc.

Andrea Gibson – Employee – Genentech, Inc., a member of the Roche Group, and holds equity and/or options in Roche.

Judy Sy – Employee – Genentech, Inc., a member of the Roche Group, and holds equity and/or options in Roche.

Amy Chen Rundle – Employee – Genentech, Inc., a member of the Roche Group, and holds equity and/or options in Roche.

J. Jill Hopkins – Employee – Genentech, Inc., a member of the Roche Group, and holds equity and/or options in Roche.

Roman G. Rubio – Employee – Genentech, Inc., a member of the Roche Group, and holds equity and/or options in Roche.

Jason S. Ehrlich – Employee – Genentech, Inc., a member of the Roche Group, and holds equity and/or options in Roche.

Sponsored by Genentech, Inc. The sponsor worked closely with an investigator steering committee to address matters such as study design and patient recruitment and retention. The sponsor participated in design and conduct of the studies, data collection, analysis, and interpretation of results, and preparation, review, and approval of the manuscript. Support for third-party writing assistance by Ivo Stoilov, MD, CMPP of Envision Scientific Solutions was provided by Genentech, Inc.

A list of members of the RISE and RIDE Research Group is available at http://aaojournal.org.

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