Elsevier

Ophthalmology

Volume 122, Issue 1, January 2015, Pages 146-152
Ophthalmology

Original article
Comparison of Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration According to LUCAS Treat-and-Extend Protocol

Presented at: The American Academy of Ophthalmology Subspecialty Day, New Orleans, Louisiana, November 15–16, 2013.
https://doi.org/10.1016/j.ophtha.2014.07.041Get rights and content

Purpose

To compare the efficacy and safety of bevacizumab versus ranibizumab when administered according to a treat-and-extend protocol for the treatment of neovascular age-related macular degeneration (AMD).

Design

Multicenter, randomized, noninferiority trial with a noninferiority limit of 5 letters.

Participants

Patients aged ≥50 years with previously untreated neovascular AMD in 1 eye and best-corrected visual acuity (BCVA) between 20/25 and 20/320.

Methods

Patients were randomly assigned to receive ranibizumab 0.5 mg or bevacizumab 1.25 mg intravitreal injections. Monthly injections were given until inactive disease was achieved. The patients were then followed with a gradual extension of treatment interval by 2 weeks at a time up to a maximum of 12 weeks. If signs of recurrent disease appeared, the treatment interval was shortened by 2 weeks at a time.

Main Outcome Measures

Change in visual acuity at 1 year.

Results

Between March 2009 and July 2012, 441 patients were randomized at 10 ophthalmological centers in Norway. The 1-year visit was completed by 371 patients. In the per protocol analysis at 1 year, bevacizumab was equivalent to ranibizumab, with 7.9 and 8.2 mean letters gained, respectively (95% confidence interval [CI] of mean difference, −2.4 to 2.9; P = 0.845). The intention-to-treat analysis was concordant. There was no significant difference in measured central retinal thickness (CRT), with a mean decrease of −112 μm for bevacizumab and −120 μm for ranibizumab (95% CI of mean difference, −13 to 28; P = 0.460). There was a statistically significant difference (P = 0.001) between the drugs regarding the number of treatments: 8.9 for bevacizumab and 8.0 for ranibizumab. There were fewer arteriothrombotic events in the bevacizumab group (1.4%) than in the ranibizumab group (4.5%) (P = 0.050) and significantly more cardiac events in the ranibizumab group (P = 0.036). However, patients treated with ranibizumab more often had a history of myocardial infarction (P = 0.021).

Conclusions

Bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year when administered according to a treat-and-extend protocol. The visual acuity results at 1 year were comparable to those of other clinical trials with monthly treatment. The numbers of serious adverse events were small.

Section snippets

Study Patients

Between March 2009 and July 2012, 441 patients with neovascular AMD at 10 ophthalmological centers in Norway were included in a multicenter, double-blind, noninferiority trial. The patients were randomized to receive intravitreal injections of ranibizumab 0.5 mg or bevacizumab 1.25 mg in a 1:1 ratio, following a treat-and-extend protocol. Eligibility criteria included age ≥50 years, previously untreated active neovascular AMD in 1 eye, and best-corrected visual acuity (BCVA) between 20/25 and

Patients and Treatments

In total, 441 randomized patients were included in the safety analysis. All 9 patients from 1 study center were excluded because of serious protocol violations, and 1 patient was excluded after a serious retinal and vitreous hemorrhage a few days after inclusion. The remaining 431 patients were included in the intention-to-treat analysis. The per protocol analyses were performed on 371 patients who completed the 1-year visit (86%). Twenty patients were nonresponders. Of the 40 patients

Discussion

At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to a treat-and-extend protocol. The mean increase in BCVA was 7.9 letters in the bevacizumab group and 8.2 letters in the ranibizumab group. The improvement in visual acuity with the treat-and-extend regimen was comparable to monthly treatment in the CATT, in which the mean increase in BCVA was 8.0 letters in the bevacizumab group and 8.5 letters in the ranibizumab group.10 Thus, excellent

Acknowledgments

The authors thank the participating principal investigators in LUCAS. Norway: Lars Haakon Berger, MD, Department of Ophthalmology, Ostfold Hospital, Fredrikstad; Vegard Forsaa, MD, Department of Ophthalmology, Stavanger University Hospital, Stavanger; Kristian Fossen, Department of Ophthalmology, University Hospital of Northern Norway; Inger Gjertsen, Department of Ophthalmology, Vestre Viken Hospital, Drammen; Emina Hadzalic-Gradas, MD, Department of Ophthalmology, Betanien Hospital, Skien;

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Financial Disclosure(s): The author(s) have made the following disclosure(s): K.B.: participated in one advisory board meeting for aflibercept for Bayer AB, Bayer Pharmaceuticals, in Sweden.

Funded by the Oslo University Hospital, Oslo, Norway. The funding organization had no role in the design of the study but aided in the conduct of the study and data management.

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