Treatment with ranibizumab in aflibercept inadequate AMD responders led to visual acuity improvement: The "ELEVATE" Study

Rouvas et al carried a non-interventional, prospective study mainly aimed to provide real-world data on the six month effects of ranibizumab on anatomical and visual acuity outcomes in eyes with active neovascular AMD, that were previously treated with aflibercept and showed inadequate response, in a representative sample of patients treated in the routine care of Greece.Prospective, observational study performed in eight ophthalmology hospital/private clinics in Greece, enrolling consented patients with active wAMD, ≥50 years-old, who had initiated ranibizumab ≥28 days and < 2 months after their last aflibercept injection. Data were collected at enrollment, and at 1, 3 and 6 months post-treatment onset (post-baseline).

Between September-2015 and November-2017, 103 eligible patients were consecutively enrolled. The age at AMD diagnosis in the study eye was 71.3±8.8 years.

Aflibercept (median of 5 injections received over 11.3 months) had been discontinued for anatomical (in 69.9%) and/or functional (38.8%) reasons.

At baseline (median: 24.3 months after wAMD diagnosis), choroidal neovascularization was occult in 69.1% of evaluable study eyes; 60.2% of the study eyes had pigment epithelial detachment (PED); 42.7% cysts; 21.4% fibrosis; 66.0% subretinal, and 59.2% intraretinal fluid.

At 6 months post-baseline: a median of 3 ranibizumab injections (range: 1–6) had been received; the best-corrected visual acuity (BCVA)≥0 letter gain rate was 81.8%; the BCVA ≥15 letter gain rate was 17.0%; BCVA gain was 3.2 letters [mean increase: 3.2±10.0 letters; median: 0.0; p = 0.002]; PED greatest basal diameter (GBD; median: 1470.5 μm) also decreased (median decrease: 114.0 μm; p = 0.019). Baseline central retinal thickness (CRT; median: 312.0 μm) remained unchanged.

One patient permanently discontinued ranibizumab due to adverse event occurrence, assessed as not causally related to ranibizumab. There were no ranibizumab-related adverse reactions.

The study indicates that ranibizumab improves visual acuity and certain anatomic outcomes after only 6 months of treatment, even when fewer than the recommended injections are administered. Additionally, physicians ranked the ease of administration of ranibizumab as better (58%) or the same (39%) as that of aflibercept in the vast majority of the patients.

Regarding anatomic outcomes, CRT remained stable throughout the observation period, whereas a statistically significant mean decrease of 46.5 μm in PED height from baseline to 6 months (using LOCF imputation) was noted (matching the 46-μm mean change assumed for sample size estimation), while significant mean decreases were also observed in PED GBD of 114.0 μm based on as-observed data and of 143.0 μm using LOCF imputation.

Overall, the study demonstrated that in the routine care of Greece, patients with wAMD receive fewer ranibizumab injections than those that would be administered under the approved dosage schedule. Under these conditions, after approximately 6 months of treatment, the patients' visual acuity improved, modest improvements in PED dimensions were noted, and CRT remained stable Further real-world evidence is needed from studies more closely matching the approved dosage scheme, in order to identify predictors of early response, aiming to enhance outcomes in patients with wAMD who have inadequately responded to prior aflibercept treatment and to further delay the progression of the disease.

Source: Rouvas et al; Clinical Ophthalmology 2022:16