An expert clinical research team, based at the University of Bonn, Germany, has reported a short-term real-world outcome study for intravitreal brolucizumab for neovascular AMD. The clinical research study was based in a single European centre to collect functional, anatomical and adverse outcomes to support nAMD patients. According to the researchers, results of the real-world outcome study has indicated that a “switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents”.
The research study has shown that real-world outcomes may often identify slightly different results in the setting of a prospective randomised clinical trial. In addition, in a real-world setting, a range of many factors can impact the actual treatment outcome of a given drug, such as non-adherence issues, or different sub-phenotypes, or other medical conditions. In respect of nAMD patients, brolucizumab (or “RTH258”) was approved by the FDA in October 2019 and on February 13th 2020 by the EMA. This innovation was a humanized single-chain antibody fragment (scFv), a molecule of 26 kDa with inhibition of, and high affinity to, all VEGF-A isoforms. The antibody inhibits activation of VEGF receptors through prevention of the ligand-receptor interaction. Inhibition of the VEGF pathway has been shown to hinder the growth of neovascular lesions and suppress endothelial cell proliferation and vascular permeability.
In the current study, patients that were previously treated with anti-VEGF treatments (such as ranibizumab, aflibercept or bevacizumab) may show recalcitrant fluid accumulations by optical coherence tomography. Following a switch to brolucizumab, the real-world outcome study showed that sixty-three eyes (of 57 patients) with nAMD (52.6% females), with a mean (±SD) age of 79.5±6.7 years, had a mean change of BCVA of 0.03±0.14 logMAR (p=0.115). The researchers additionally found that significant reductions were recorded for FCP (foveal centre point) with a mean (±SD) change of −66.81±72.63 μm, −66.76±60.71 μm for CSRT (central subfield retinal thickness), and −0.27±0.24 mm³ for macular volume (all p<0.001). Finally, intraocular inflammation was observed in seven eyes of seven patients, including one case of retinal vasculitis. While the study was relatively small, with a relatively short duration of study, the authors of the paper have commented that, “[o]ur findings indicate that initiation of intravitreal brolucizumab therapy in previously treated patients with nAMD (switch) may be an option in particular with regard to the morphological effects in recalcitrant cases who previously received multiple anti-VEGF injections without satisfactory resolution of fluid in various anatomical compartments”.