Elsevier

Ophthalmology

Volume 122, Issue 12, December 2015, Pages 2504-2513.e1
Ophthalmology

Original article
Outcomes with As-Needed Ranibizumab after Initial Monthly Therapy: Long-Term Outcomes of the Phase III RIDE and RISE Trials

Presented at: the American Academy of Ophthalmology, November 16–19, 2013, New Orleans, Louisiana; American Society of Retina Specialists, August 9–13, 2014, San Diego, California; American Diabetes Association, July 13–17, 2014, San Francisco, California; Association for Research in Vision and Ophthalmology, May 4–8, 2014, Orlando, Florida; Macula Society, February 19–22, 2014, Key Largo, Florida; European Society of Retina Specialists, September 11–14, 2014, London, United Kingdom.
https://doi.org/10.1016/j.ophtha.2015.08.006Get rights and content
Under a Creative Commons license
open access

Purpose

To determine whether the efficacy and safety achieved with monthly ranibizumab as treatment for diabetic macular edema (DME) can be maintained with less-than-monthly treatment.

Design

Open-label extension (OLE) phase of randomized, sham-controlled phase III trials: RIDE (NCT00473382) and RISE (NCT00473330).

Participants

Five hundred of 582 adults who completed the 36-month randomized core studies elected to enter the OLE.

Methods

All patients participating in the OLE were eligible to receive 0.5 mg ranibizumab according to predefined re-treatment criteria: Treatment was administered when DME was identified by the investigator on optical coherence tomography or when best-corrected visual acuity (BCVA) worsened by ≥5 Early Treatment Diabetic Retinopathy Study letters versus month 36. Patients were observed at 30-, 60-, or 90-day intervals depending on the need for treatment.

Main Outcome Measures

The incidence and severity of ocular and nonocular events, proportion of patients with ≥15-letter best-corrected visual acuity (BCVA) gain from baseline, mean BCVA change from month 36 (final core study visit), mean central foveal thickness (CFT), and mean CFT change from month 36.

Results

A mean of 4.5 injections were administered over a mean follow-up of 14.1 months. Approximately 25% of patients did not require further treatment based on protocol-defined re-treatment criteria. Mean BCVA was sustained or improved in these patients through the end of follow-up. Approximately 75% of patients received ≥1 criteria-based re-treatment; mean time to first re-treatment was approximately 3 months after the last masked-phase visit. Mean BCVA remained stable in re-treated patients; CFT was generally stable with a trend toward slight thickening in all patients when mandatory monthly therapy was relaxed.

Conclusions

Vision gains achieved after 1 or 3 years of monthly ranibizumab therapy were maintained with a marked reduction in treatment frequency; some patients required no additional treatment. These observations are consistent with other studies evaluating induction followed by maintenance ranibizumab therapy for DME. Patients whose treatment was deferred by 2 years (randomized initially to sham) did not ultimately achieve the same BCVA gains as patients who received ranibizumab from baseline. Ranibizumab's safety profile in the OLE appeared similar to that observed in the controlled core studies and other studies.

Abbreviations and Acronyms

AE
adverse event
BCVA
best-corrected visual acuity
CFT
central foveal thickness
DME
diabetic macular edema
DR
diabetic retinopathy
DRSS
diabetic retinopathy severity score
ETDRS
Early Treatment Diabetic Retinopathy Study
FDA
Food and Drug Administration
NPDR
nonproliferative diabetic retinopathy
OCT
optical coherence tomography
OLE
open-label extension
PDR
proliferative diabetic retinopathy
PRN
pro re nata
SAE
serious adverse event
VEGF
vascular endothelial growth factor

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Supplemental material is available at www.aaojournal.org.

Financial Disclosure(s): The author(s) have made the following disclosure(s): D.S.B.: Consultant − Alcon, Allergan, Eyetech, Genentech, Inc., Novartis/QLT, Neurotech, Pfizer, Regeneron, Allegro, Ohr; Speakers Bureau – Alcon, Allergan, Genentech, Inc., Pfizer; Clinical Research Projects: Alcon, Allergan, Genentech, Inc., Pfizer, Regeneron.

Q.D.N.: Research Grants − Genentech, Inc., Regeneron, Pfizer; Advisory boards: Genentech, Inc., AbbVie, Regeneron; Consultant: Santen Pharmaceuticals, Bausch & Lomb.

D.M.B.: Research Grants − Genentech, Inc., Regeneron, Novartis, Alcon, Allergan, Alimera Sciences, Eli Lilly, Molecular Partners, Ophthotech, Abbott, Schering Plough, Othera Pharmaceuticals, Paloma Pharmaceuticals, Neurotech, TargeGen, Sirion Therapeutics, Inc., Jerini AG; Consultant: Genentech, Inc., Regeneron, Allergan, Alcon, Molecular Partners, Novartis, Oraya Therapeutics, Paloma Pharmaceuticals, Steba Biotech; Speakers Bureau – Genentech, Inc.

K.B.: Employee − Genentech, holds Roche stock/stock options.

J.S.E.: Employee − Genentech, holds Roche stock/stock options.

Supported by Genentech, Inc. Support for third-party writing assistance was provided by Genentech, Inc. The sponsor participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation and review of the manuscript.

Author Contributions:

Conception and design: Boyer, Nguyen, Brown, Basu, Ehrlich

Data collection: Boyer, Nguyen, Brown, Basu, Ehrlich

Analysis and interpretation: Boyer, Nguyen, Brown, Basu, Ehrlich

Obtained funding: Not applicable

Overall responsibility: Boyer, Nguyen, Brown, Basu, Ehrlich

The RIDE and RISE Research Group is listed in the Appendix (available at www.aaojournal.org).