Elsevier

Ophthalmology

Volume 120, Issue 10, October 2013, Pages 2013-2022
Ophthalmology

Original article
Long-term Outcomes of Ranibizumab Therapy for Diabetic Macular Edema: The 36-Month Results from Two Phase III Trials: RISE and RIDE

Presented at: the 35th Annual Macula Society Meeting, June 11–15, 2012, Jerusalem, Israel; the US Food and Drug Administration Dermatologic and Ophthalmic Drugs Advisory Committee Meeting, July 26, 2012, Silver Spring, Maryland; the 30th Annual Meeting of the American Society of Retina Specialists, August 25–29, 2012, Las Vegas, Nevada; the 12th EURETINA Meeting, September 6–9, 2012, Milan, Italy; the 45th Annual Retina Society, October 5–7, 2012, Washington, DC; and the Joint Meeting of the American Academy of Ophthalmology and the Asia-Pacific Academy of Ophthalmology, November 9–13, 2012, Chicago, Illinois.
https://doi.org/10.1016/j.ophtha.2013.02.034Get rights and content
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Purpose

To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME).

Design

Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection–controlled for 2 years.

Participants

Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥275 μm on optical coherence tomography.

Methods

Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary.

Main Outcome Measures

The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24.

Results

Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group.

Conclusions

The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Cited by (0)

Financial Disclosure(s): The author(s) have made the following disclosure(s): D.M.B.: grants to investigator's institution (Genentech, Inc., Regeneron/Bayer, Allergan, Alimera, GSK, Pfizer, ThromboGenics, Quark), consultancy (Regeneron/Bayer, Alimera, ThromboGenics, Novartis), Speakers' Bureau (Regeneron/Bayer); Q.D.N.: grants to investigator's institution (Genentech, Inc., Regeneron, Pfizer, Abbott, Lux, GSK, Optos, Heidelberg Engineering), consultancy (Santen Pharmaceutical Co. Ltd., Bausch & Lomb); D.M.M.: grants to investigator's institution (Allergan, Genentech, Inc., Pfizer, Regeneron, ThromboGenics, Quark, Lpath), Speakers' Bureau (Genentech, Inc., Regeneron), advisory board (Genentech, Inc., Regeneron, ThromboGenics), consultancy (Genentech, Inc., Regeneron, ThromboGenics); D.S.B.: consultancy (Alcon, Allergan, Bausch & Lomb, Bayer, Genentech, Inc., Merck, Regeneron), Speakers' Bureau (Alcon, Allergan, Regeneron); S.P.: consulting fee (Genentech, Inc.), stock/stock options (Ophthotech); L.F.: consultancy (Roche), Speakers' Bureau (Roche, Regeneron, ThromboGenics, Bayer); G.S. has no potential conflicts of interest; A.C.R., J.Z., J.J.H., R.G.R., A.P.A., and J.S.E. are employees of Genentech, Inc., are members of the Roche Group, and hold equity or options in Roche.

Sponsored by Genentech, Inc. 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.

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

A full listing of the RIDE and RISE Research Group is available as an online supplement to Nguyen et al. Ophthalmology 2012;119:789–801.

§

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