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Does a treat-and-extend approach with potentially less frequent anti-vascular endothelial growth factor injections and visits provide visual outcomes not worse than monthly ranibizumab injections in patients with neovascular acute macular degeneration?
In this randomized clinical trial of 580 patients with treatment-naive choroidal neovascularization secondary to acute macular degeneration, at month 24, visual acuity outcomes in the treat-and-extend group were not worse than those in the monthly group. This outcome occurred despite a mean of 17.6 injections and visits in the treat-and-extend group compared with 23.5 in the monthly group.
These 2-year outcomes, combined with those of 1-year trials, appear to support the hypothesis that treat-and-extend regimens are not worse than monthly treatment with ranibizumab for patients with neovascular acute macular degeneration similar to patients enrolled and treated in this trial.
Although the Canadian Treat-and-Extend Analysis Trial With Ranibizumab in Patients With Neovascular Age-Related Macular Disease (CANTREAT) reported herein and the Treat and Extend study provided data to show noninferiority of treat-and-extend (T&E) at 12 months, to date there are few data on 24-month T&E trials compared with monthly dosing.
To compare the efficacy of ranibizumab using a T&E regimen to monthly dosing in treatment-naive patients with neovascular age-related macular degeneration (nAMD) after 24 months.
Design, Setting, and Participants
A randomized, open-label, multicenter, noninferiority intention-to-treat trial with a margin of −5 letters in best-corrected visual acuity (BCVA) from baseline to 12 months between groups was conducted at 27 treatment centers in Canada. Participants included 580 patients with treatment-naive choroidal neovascularization secondary to AMD. The study was conducted from May 8, 2013, to August 28, 2018, and data analysis was performed between August 29 and September 12, 2018.
Patients with nAMD were randomized 1:1 to receive intravitreal ranibizumab, 0.5 mg, in either a T&E or monthly dosing regimen.
Main Outcomes and Measures
Mean change in BCVA in Early Treatment of Diabetic Retinopathy Study letters from baseline to month 24.
Of the 580 randomized patients, 350 were women (60.3%) and 547 were white (94.3%). Mean (SD) age was 78.8 (7.8) years. By the end of month 24, 466 of the 580 randomized patients (80.3%) had completed the study and participants in the T&E arm received a mean of 17.6 injections compared with 23.5 injections for the monthly arm, for a difference of 5.9 injections and visits over 2 years (95% CI, 5.4-6.5; P < .001). The mean (SD) BCVA improvement was not worse with the T&E arm, 6.8 (14.1) letters vs 6.0 (12.6) letters, compared with the monthly arm (difference, 0.9; 95% CI, −1.6 to 3.3; P = .21). There was a gain of 15 or more letters in 25.5% of the T&E group and 23.1% of the monthly treatment group (difference, 2.4%; 95% CI, −6.8% to 11.6%; P = .59) and a loss of 15 or more letters in 6.5% of the T&E group and 5.8% of the monthly treatment group (difference, −0.7%; 95% CI, −9.9% to 8.5%; P = .85).
Conclusions and Relevance
These findings suggest that change in vision from baseline is not worse with a T&E compared with a monthly regimen of ranibizumab for nAMD through 24 months, achieving clinically meaningful improvements in BCVA despite fewer injections and visits.
ClinicalTrials.gov identifier: NCT02103738
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Accepted for Publication: November 4, 2019.
Published Online: January 9, 2020. doi:10.1001/jamaophthalmol.2019.5540
Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2020 Kertes PJ et al. JAMA Ophthalmology.
Corresponding Author: Peter J. Kertes, MD, CM, The John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Room M1-202a, Toronto, ON M4N 3M5, Canada (firstname.lastname@example.org).
Author Contributions: Drs Kertes and Sheidow had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Kertes, Galic, Greve, Williams, Sheidow.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Galic.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Baker, Lahaie.
Obtained funding: Kertes.
Administrative, technical, or material support: Galic, Baker.
Supervision: All authors.
Conflict of Interest Disclosures: Dr Kertes reported receiving grants, personal fees, and nonfinancial support from Novartis during the conduct of the study; personal fees and nonfinancial support from Bayer, grants from Allergan, and grants from Roche outside the submitted work; and holds stock in ArcticDx. Dr Greve reported receiving grants from Novartis during the conduct of the study and Shareholder Secure Diagnostic Imaging (tele ophthalmology company, with no direct conflict). Dr Williams reported receiving grants and personal fees from Novartis during the conduct of the study, grants and personal fees from Bayer and Allergan, and grants from Roche and Chengndu Kanghong Biotech outside the submitted work. Drs Baker and Lahaie are employees of Novartis Pharmaceuticals Canada Inc. Dr Sheidow reported serving as an advisory board member for Novartis, Bayer, and Allergan, for which he received honoraria. No other disclosures were reported.
Funding/Support: This study was funded by Novartis Pharmaceuticals Canada Inc.
Role of the Funder/Sponsor: Novartis Pharmaceuticals Canada Inc participated in the study design and the conduct of the study, oversight in the collection and management of the data, analysis and interpretation of the data, and preparation and review of the manuscript.
Meeting Presentation: These study results were presented at the Annual Meeting of the American Academy of Ophthalmology; Chicago, Illinois; October 28, 2018; the Canadian Retina Society Annual Meeting; Whistler, British Columbia, Canada; March 7, 2019; and the Canadian Ophthalmological Society Meeting; Québec City, Québec, Canada; June 15, 2019.
Data Sharing Statement: See Supplement 2.
Additional Contributions: The CANTREAT steering committee and Novartis Pharmaceuticals Canada Inc thank Radmila Day, MSc (SNELL Medical Communication), who prepared a manuscript draft for the authors to edit; this contribution was funded as part of the study by Novartis Pharmaceuticals Canada Inc. We also thank the CANTREAT study investigators.
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