Elsevier

Ophthalmology

Volume 120, Issue 5, May 2013, Pages 1046-1056
Ophthalmology

Original article
Twelve-Month Efficacy and Safety of 0.5 mg or 2.0 mg Ranibizumab in Patients with Subfoveal Neovascular Age-related Macular Degeneration

Portions of these data were presented at the American Academy of Ophthalmology Subspecialty Day and Annual Meeting, October 22–25, 2011, Orlando, Florida; Macula 2012, January 20–21, 2012, New York, New York; the World Ophthalmology Congress, February 16–20, 2012, Abu Dhabi, United Arab Emirates; the Association for Research in Vision and Ophthalmology Annual Meeting, May 6–10, 2012, Fort Lauderdale, Florida; the 35th Annual Macula Society Meeting, June 11–15, 2012, Jerusalem, Israel; and the 12th EURETINA Congress, September 6–9, 2012, Milan, Italy.
https://doi.org/10.1016/j.ophtha.2012.10.014Get rights and content
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Objective

To evaluate the 12-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly and on an as-needed (PRN) basis in treatment-naïve patients with subfoveal neovascular age-related macular degeneration (wet AMD).

Design

A 24-month, phase III, randomized, multicenter, double-masked, dose-response study.

Participants

Patients aged ≥50 years with subfoveal wet AMD.

Methods

Patients (n = 1098) were randomized to receive ranibizumab 0.5 mg or 2.0 mg intravitreal injections administered monthly or on a PRN basis after 3 monthly loading doses.

Main Outcome Measures

The primary efficacy end point was the mean change from baseline in best-corrected visual acuity (BCVA) at month 12. Key secondary end points included the mean number of ranibizumab injections, the mean change from baseline in central foveal thickness (CFT) over time, and the proportion of patients who gained ≥15 letters of BCVA. Unless otherwise specified, end point analyses were performed using the last-observation-carried-forward method to impute missing data.

Results

At month 12, the mean change from baseline in BCVA for the 4 groups was +10.1 letters (0.5 mg monthly), +8.2 letters (0.5 mg PRN), +9.2 letters (2.0 mg monthly), and +8.6 letters (2.0 mg PRN). The proportion of patients who gained ≥15 letters from baseline at month 12 in the 4 groups was 34.5%, 30.2%, 36.1%, and 33.0%, respectively. The mean change from baseline in CFT at month 12 in the 4 groups was −172.0 μm, −161.2 μm, −163.3 μm, and −172.4 μm, respectively. The mean number of injections was 7.7 and 6.9 for the 0.5-mg PRN and 2.0-mg PRN groups, respectively. Ocular and systemic safety profiles were consistent with previous ranibizumab trials in AMD and comparable between groups.

Conclusions

At month 12, the ranibizumab 2.0 mg monthly group did not meet the prespecified superiority comparison and the ranibizumab 0.5 mg and 2.0 mg PRN groups did not meet the prespecified noninferiority (NI) comparison. However, all treatment groups demonstrated clinically meaningful visual improvement (+8.2 to +10.1 letters) and improved anatomic outcomes, with the PRN groups requiring approximately 4 fewer injections (6.9–7.7) than the monthly groups (11.2–11.3). No new safety events were observed despite a 4-fold dose escalation in the study. The pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) study confirmed that ranibizumab 0.5 mg dosed monthly provides optimum results in patients with wet AMD.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Cited by (0)

Manuscript no. 2012-465.

Financial Disclosure(s): The author(s) have made the following disclosure(s): B.G.B. has served as a consultant for Alimera, Elan, Genentech, Synergetics, and Thrombogenics; has received research funding from Genentech; is a member of the speakers bureau for Genentech and Regeneron; and has received royalties from AKORN. A.C.H. has served as a consultant for Alcon, Allergan, Centocor/Johnson & Johnson, Genentech, Merck, NeoVista, Ophthotech, Oraya, Paloma, PRN, QLT, Regeneron, and Thrombogenics; has received research funding from Alcon, Allergan, Genentech, National Eye Institute/National Institutes of Health, NeoVista, Ophthotech, Oraya, PRN, QLT, Regeneron, and Second Sight; and is a member of the speakers bureau for Alcon, Genentech, and Regeneron. D.M.B. has served as a consultant for Alcon, Alimera, Allergan, Genentech, Novartis, Regeneron, and Thrombogenics; has received research funding from Abbott, Alcon, Alimera, Allergan, Eli Lilly, Genentech, GlaxoSmithKline, Ophthotech, Novartis, Regeneron, and Thrombogenics; and is a member of the speakers bureau for Genentech and Regeneron. J.S.H. has served as a consultant for Acucela, Allergan, Bayer, Forsight, Fovea, Genentech, Genzyme, GlaxoSmithKline, LPath, Neovista, Oraya, Paloma, QLT, Quark, and Regeneron; and has received research funding from Alcon, Alimera, Allergan, Fovea, Genentech, Genzyme, GlaxoSmithKline, Neovista, Neurotech, Novartis, Ophthalmic Consultants of Boston, Ophthotech, Paloma, and Regeneron. I.J.S. has served as a consultant for Genentech, Eyetech, Regeneron, and Thrombogenics; has received research funding from Genentech; is a member of the speakers bureau for Genentech, Optos, and Regeneron; and is a board member of Optos. Z.L., R.G.R., and P.L. are employees of Genentech. Support for third-party writing assistance for this manuscript provided by Linda Merkel, PhD, and Michelle Kelly, PhD, of UBC-Envision Group, and was provided by Genentech, Inc.

Funding: Genentech, Inc. (South San Francisco, CA) provided support for the study and participated in the study design; conducting the study; and data collection, management, and interpretation.

*Group members listed online in Appendix 1 (available at http://aaojournal.org).

Group members of the HARBOR Study Group are listed online (available at http://www.aaojournal.org).