Brolucizumab Anti-Drug Antibodies May Increase Inflammation Risk

Eye Injection
The study also found an association between the anti-VEGF drug and retinal occlusive vasculitis.

Brolucizumab anti-drug antibodies (ADAs) may be a risk factor for intraocular inflammation (IOI) and retinal occlusive vasculitis, according to new research from Acta Ophthalmologica.

Case series have recently reported intravitreal injections of the anti vascular endothelial growth factor (VEGF) drug brolucizumab may increase risk of IOI and occlusive retinal vasculitis. 

Researchers collected and analyzed samples (192 serum 54 vitreous) of 54 patients to compare occurrence of brolucizumab ADAs and ranibizumab ADAs among patients with ocular diseases. The investigators utilized indirect enzyme-linked immunosorbent assay (ELISA) to analyze the samples for immune globulin (Ig) G ADAs.

Optical density (OD) was read at 450 nm (wavelength correction at 550 nm) and defined as a notable ADA if it exceeded 0.1.

Serum samples had higher frequency of notable ADA signals and greater mean ADA signals for brolucizumab compared with ranibizumab. Mean OD of the serum samples was very low for ranibizumab ADAs (5 notable ODs).

A pair of the patients experienced severe IOI and occlusive retinal vasculitis after intravitreal brolucizumab. They had high ODs in the anti-brolucizumab antibody ELISA. One of the 2 patients had high brolucizumab ADA levels in both serum and vitreous samples. One patient with low brolucizumab ADA serum levels developed moderate IOI without retinal vasculitis.

The notable ADA signals were less frequent in vitreous samples (13.0%) compared with corresponding serum samples (20.4% McNemar’s test P =.289). Notable brolucizumab ADA levels were higher among vitreous samples from patients with diabetic retinopathy (DR). In 6 of 7 cases, patients whose vitreous samples had notable brolucizumab ADA levels had not previously received brolucizumab.

“Taken together, in our cross-sectional study population including both brolucizumab-treated and treatment-naive patients, we detected ADAs to brolucizumab or pre-existing antibodies cross-reacting with brolucizumab,” the researchers explain. “The ADA signal was stronger and more frequent for brolucizumab than for ranibizumab. Taking previous observations and our data into consideration, anti-brolucizumab ADAs may represent a risk factor for IOI and retinal occlusive vasculitis in patients treated with brolucizumab.”

Limitations of the study included the small number of cases with IOI or retinal vasculitis after receiving brolucizumab.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Busch M, Pfeil JM, Dähmcke M, et al. Anti-drug antibodies to brolucizumab andranibizumab in serum and vitreous of patients with ocular disease. Acta Ophthalmol. Published online February 28, 2022. doi:10.1111/aos.15124