Brolucizumab Therapy Extends Intervals Between Anti-VEGF Injections

Patients who underwent more frequent anti-VEGF injections for neovascular AMD treatment before switching to brolucizumab experienced the greatest extension in intervals after switching.

Brolucizumab therapy extends intervals necessary between anti-vascular endothelial growth factor (anti-VEGF) treatments in patients with neovascular age-related macular degeneration (nAMD), according to research published in Ophthalmology. The extensions are most notable in treatment-experienced patients who previously required more frequent intravitreal injections, the study shows.

Initial studies show brolucizumab therapy extends intervals between treatments after prior therapy with other anti-VEGF agents — now an analysis drawing on a database of more than 850,000 US patients with nAMD reveals close to 59% of eyes in a cohort of 1890 participants who switched to the new drug achieved extension with stable or gained visual acuity (VA).

Researchers reviewed records from individuals from the Intelligent Research in Sight (IRIS®) Registry to evaluate how switching to brolucizumab therapy extends intervals of treatment. The study excluded patients receiving other anti-VEGF drugs after the first, index brolucizumab injection, as well as not having a treatment with the new biologic once during months 0 to 6 and again in months 6 to 12.

Extension was defined as reaching a treatment interval extension of 2 weeks or longer at 12 months compared with time between injections of the previous regimen, while maintaining or improving VA. Of the population, 2015 eyes of the 1890 patients met all study requirements, and for these, 1186 eyes (58.9%) were extenders, and 829 (41.1%) nonextenders. 

Demographic variables such as age, gender, and comorbid conditions had only limited bearing on the likelihood of extending a patient’s injection interval.

The chief factor in achieving extension proved to be a shorter average pre-switch duration of 5.9(±2.1) weeks, compared with 10.1(±7.6) weeks for non-extenders. In a statistical model with non-normalized variables, pre-switch period of fewer than 8 weeks significantly raised the chance for extension; the adjusted odds ratio was 5.6 (95% CI 4.5, 6.9) vs those having 8 weeks or longer (P <.001). Although previous reports concluded that longer intervals did not depend on BCVA at index dose of brolucizumab, the present larger cohort demonstrates that individuals with the highest VA at index have 1.72-fold greater odds for extension than those with 40 to 65 letters. 

The most treatment-experienced patients (those who required more frequent injections before switching) had the greatest brolucizumab therapy extended intervals, according to the report. 

“Demographic variables such as age, gender, and comorbid conditions had only limited bearing on the likelihood of extending a patient’s injection interval,” report the researchers. “A complicated or extensive medical history therefore does not appear to preclude a positive clinical outcome after switching to brolucizumab therapy.”

Reports indicate brolucizumab may be connected to a 2.4% or 4.6% incidence of intraocular inflammation (IOI); retinal vasculitis or retinal vascular occlusion. Novartis Pharma AG released a label update in May 2021 advising brolucizumab should not be administered less than 8 weeks apart after 3 (1 per month) loading doses, the investigators noted. In the current analysis, ocular adverse events occurred for 1.4% of eyes losing letters, 1.0% of those maintaining VA, and 1.0% of eyes with vision improvement.

Limitations of this study included no imaging to support positive outcome data, and lack of cause noted for the jump to brolucizumab. In real-world practice, patients may benefit from this drug even when an extension of 2 weeks or more is not reached or there is no VA improvement, because of the potential for greater retinal drying.

Disclosures: This trial was supported with funds from Novartis Pharma AG, also involved in conduct of the study. Several investigators have disclosed affiliations with Novartis and/or the biotech, medical device, or pharmaceutical industries. Please see the original reference for complete disclosures. 


MacCumber MW, Wykoff CC, Karcher H, et al. Factors linked to injection interval extension in eyes with wet age-related macular degeneration switched to brolucizumab. Ophthalmol. Published online March 27, 2023. doi:10.1016/j.ophtha.2023.03.017