In this randomized, multicenter phase 3b trial, investigators analyzed the efficacy of treat-and-extend (TREX) ranibizumab for neovascular AMD.
Study design
After receiving 3 initial monthly doses of 0.5-mg ranibizumab, 60 patients with treatment-naïve neovascular AMD were randomized 1:2 to continue monthly ranibizumab or begin a TREX protocol allowing for rechallenges of the maximum treatment interval.
Upon achieving a dry macula, TREX patients had their injection interval increased by 2 week increments until fluid recurrence was noted, at which point the interval would be decreased by 2 week increments until the macula was dry again. At that point, the interval was challenged again by 1 week increments. The minimum and maximum injection intervals were preset at 4 and 12 weeks, respectively.
Outcomes
Of the 50 patients that completed 2 years of follow-up, BCVA letter gains were similar between groups: 10.5 for the monthly arm and 8.7 for the TREX arm (P=0.64). Anatomic improvements were also similar (P=0.99).
There was no difference in the proportion of patients who gained at least 15 letters. No patient in the monthly cohort lost more than 2 letters, whereas 5 TREX patients (13%) lost at least 15 letters. The cause of significant vision loss in these 5 patients was due predominantly to progressive macular atrophy rather than increased exudation from the TREX regimen.
Nearly half (47%) of TREX patients achieved stable fluid resolution at an extension interval of 8 weeks or more, and the mean maximum tolerated extension was 8.5 weeks. Most were unable to tolerate an interval longer than their initial maximum extension without experiencing fluid recurrence.
Through 2 years, the monthly cohort received an average of 25.5 injections, which was significantly higher than the 18.6 injections in the TREX cohort (P<0.001).
Limitations
The study was limited by its relatively small sample size. Additionally, outcomes could vary depending on the anti-VEGF agent.
Clinical significance
This is the first prospective, randomized study to demonstrate that a TREX regimen for AMD does not result in worse visual or anatomic outcomes through 2 years. The regimen was also effective in reducing treatment and visit burden for patients. Evidence of these benefits are especially important because TREX is the most commonly used treatment strategy in the United States according to the America Society of Retina Specialists’ Preferences and Trends (PAT) Survey.