Study: Anti-VEGF Dosing is Varied, Longer Between Than Pivotal Trial Rates

A review of 3 different anti-vascular endothelial growth factor (anti-VEGF) agents for neovascular age-related macular degeneration (nAMD) found that there’s substantial variation in the treatments’ dosing intervals, and successive anti-VEGF injections are longer between than reported in clinical trials.

In a review of bevacizumab (Avastin), ranibizumab (Lucentis), and aflibercept (Eylea) for nAMD, researchers sought real-world clinical understanding of usage patterns for anti-VEGFs. The results were published at the 121^st Annual Meeting of the American Academy of Ophthalmology (AAO 2017) in New Orleans, LA.

The study was lead by Arghavan Almony, MD, from Carolina Eye Associates in Southern Pines, NC. She and colleagues reviewed the Vestrum Electronic Health Record’s (VEHR) databse for US retina specialists in private practices.

The studied patients — those receiving one of the 3 anti-VEGF injection therapies for nAMD between January 1, 2013, and July 31, 2014 —were studied in their treatment frequency based on data from at least 6 months before and 12 months after the initial intravitreal injection (IVI).

The researchers tracked injection frequency inclusive of IVI during a follow-up period of at least 12 months, the frequency of examinations and optical coherence tomography (OCT) procedures during follow-up, and rate of therapy interruption — as defined by the proportion of patient eyes with an interval of more than 12 weeks between injections.

The 51,496 total nAMD patient eyes eligible for the set criteria were not evenly split among anti-VGEF therapies. Researchers reported that 12,635 (24%) were treated with Eylea, 19,397 (38%) with Lucentis, and 19,474 (38%) with Avastin.

The overall mean number of injections in the first 3 and 12 months of treatment was 2.3 and 5.9, respectively. Eyes treated with Eylea — a therapy labeled for administration once every 2 months after 3 initial month injections — averaged 2.3 and 6.2 injections, respectively.

Eyes treated with Lucentis — a once-monthly therapy — averaged 2.3 and 6 injections, respectively. Eyes treated with Avastin — not approved by the US Food and Drug Administration for nAMD, but used as an off-label treatment at a regimen similar to Lucentis — averaged 2.1 and 5.6 injections, respectively.

In average duration between injections, Eylea, Lucentis, and Avastin cohorts reported 63, 66, and 67 days, respectively during the 3-inection dose-loading phases. They then averaged intervals of 51, 54, and 59 days, respectively, for subsequent injections after the loading phase.

The loading dose phase duration between injections was substantially higher than what was practiced in pivotal trials for the anti-VEGF therapies. In the post-loading dose phase duration rates, only Eylea cohorts reported a shorter duration between subsequent injections than its respective pivotal trials, according to the study.

Therapy interruption was prominent among all treatment groups, with at least 50% of each therapy’s patients experiencing interruption. The overall average amount of time it took patients to reach therapy interruption was 212 days.

Researchers wrote that there was “substantial variability in reinjection interval across all treatments,” noting particularly that Eylea’s recommended 8-week administration rate in post-loading phases was seemingly disregarded. A “considerable proportion” (43.8%) of Eylea injections in post-loading phase were administered at intervals of less than 6 weeks, they wrote.

The intervals between successive injections was typically longer than its pivotal trial results, researchers concluded, although a significant proportion of patients reported shorter intervals between injections.

“There remains an unmet need for extended-duration treatments for nAMD,” researchers wrote.