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

Question  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?

Findings  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.

Meaning  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.

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