Efficacy of a Treat-and-Extend Regimen With Ranibizumab in Patients With Neovascular Age-Related Macular Disease: A Randomized Clinical Trial

Abstract

Importance: 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.

Objective: 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.

Interventions: 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.

Results: 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.

Trial registration: ClinicalTrials.gov identifier: NCT02103738.

Conflict of interest statement

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.

Figures

Figure 1.. Flow of Study Participants

Figure 2.. Change in Best-Corrected Visual Acuity (BCVA) Letters at 12- and 24-Month Follow-up

ETDRS indicates Early Treatment Diabetic Retinopathy Study; OM, once monthly; T&E, treat-and-extend.