Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study*)
A 12-month, randomized, controlled, double-masked, multicenter phase II study
- Pascale Massin, MD, PHD1,
- Francesco Bandello, MD, FEBO2,
- Justus G. Garweg, MD3,
- Lutz L. Hansen, MD4,
- Simon P. Harding, FRCOPHTH, MD5,
- Michael Larsen, MD, DMSC6,
- Paul Mitchell, MD, PHD7,
- Dianne Sharp, FRANZCO8,
- U.E.K. Wolf-Schnurrbusch, MD9,
- Margarita Gekkieva, MD10,
- Andreas Weichselberger, PHD10 and
- Sebastian Wolf, MD, PHD11
- 1Assistance Publique des Hôpitaux de Paris, Ophthalmology Department, Hôpital Lariboisière, Paris, France;
- 2Department of Ophthalmology, University of Udine, Udine, Italy;
- 3Clinic for Vitreoretinal Disease, Swiss Eye Institute and University of Bern, Bern, Switzerland;
- 4University Hospital Freiburg, Freiburg, Germany;
- 5Ophthalmology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, U.K.;
- 6Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark;
- 7Centre for Vision Research, University of Sydney, Sydney, New South Wales, Australia;
- 8Department of Ophthalmology, University of Auckland, Auckland, New Zealand;
- 9Bern Photographic Reading Center, Department of Ophthalmology, Inselspital, University Bern, Bern, Switzerland;
- 10Novartis Pharma, Basel, Switzerland;
- 11Department of Ophthalmology, Inselspital, University Bern, Bern, Switzerland.
- Corresponding author: Sebastian Wolf, .
OBJECTIVE The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.
RESEARCH DESIGN AND METHODS This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age >18 years, type 1 or 2 diabetes, central retinal thickness [CRT] ≥300 μm, and best corrected visual acuity [BCVA] of 73–39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n = 51 each) or sham (n = 49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n = 151, patients receiving ≥1 injection).
RESULTS At month 12, mean ± SD BCVA improved from baseline by 10.3 ± 9.1 letters with ranibizumab and declined by 1.4 ± 14.2 letters with sham (P < 0.0001). Mean CRT reduction was 194.2 ± 135.1 μm with ranibizumab and 48.4 ± 153.4 μm with sham (P < 0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P < 0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab.
CONCLUSIONS Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.
↵*A complete list of the RESOLVE investigators can be found in the online appendix, available at http://care.diabetesjournals.org/cgi/content/full/dc10-0493/DC1.
Clinical trial reg. no. NCT00284050, clinicaltrials.gov.
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See accompanying editorial, p. 2484.
- Received March 15, 2010.
- Accepted August 8, 2010.
- © 2010 by the American Diabetes Association.
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