Ranibizumab Effective in Some With Inadequate Response to Aflibercept

Real-world evidence shows short-term improvements in wet AMD when patients who inadequately responded to aflibercept were treated with ranibizumab.

Patients with neovascular age-related macular degeneration (wet AMD) who had an inadequate response to treatment with aflibercept may have another option, according to research published in Clinical Ophthalmology. Researchers say those patients responded well to 6-month treatments with ranibizumab, with no statistically significant changes to central retinal thickness (CRT).

The research team conducted a prospective, observational study at 8 ophthalmology clinics in Greece to evaluate the functional and anatomic effects of switching to ranibizumab in cases of wet AMD with inadequate response to aflibercept treatment.

The study included patients with active wet AMD who were 50 years of age or older and had initiated ranibizumab at least 28 days and less than 2 months after their last aflibercept injection between September 2015 and November 2017. The primary outcomes were mean change in central retinal thickness (CRT) and pigment epithelial detachment (PED) dimensions, maximal PED height and greatest basal diameter (GBD), from baseline after 6 months of treatment with ranibizumab.

A total of 103 eligible patients ( 56.3% women, 43.7% men; mean age, 74.8±8.6 years) were consecutively enrolled in the study. At AMD diagnosis in the study eye, patients had a mean age of 71.3±8.8 years. Aflibercept, with a median of 5 injections received over 11.3 months, was discontinued for anatomical reasons in 69.9% of patients and functional reasons in 38.8% of patients. 

Ranibizumab improves visual acuity and certain anatomic outcomes after only 6 months of treatment, even when fewer than the recommended injections are administered.

At baseline, which was a median of 24.3 months after wet AMD diagnosis, the researchers found that choroidal neovascularization was occult in 69.1% of evaluable study eyes. They also found PED in 60.2%, cysts in 42.7%, fibrosis in 21.4%, subretinal fluid in 66.0%, and intraretinal fluid in 59.2% of the study eyes. 

After 6 months of ranibizumab treatment, with a median of 3 ranibizumab injections (range, 1-6), the team documents that 81.8% of eyes had a best-corrected visual acuity (BCVA) gain of at least 0 letters (mean increase, 3.2±10.0 letters; median, 0.0 letters; P =.002). They reported that 17.0% of eyes had at least a15 letter gain. They also found that PED and GBD decreased (median decrease, 114.0 μm; P =.019) and that CRT remained unchanged from baseline in the ranibizumab-treated patients. 

The researchers reported that permanent discontinuation of ranibizumab due to an adverse event, found not to be causally related to ranibizumab, was required in 1 patient. They observed no adverse reactions related to ranibizumab.

“Ranibizumab improves visual acuity and certain anatomic outcomes after only 6 months of treatment, even when fewer than the recommended injections are administered,” according to the researchers. 

Limitations of the study included those related to the observational design, namely patient selection bias and information bias, missing data for change in CRT at 6 months for 30% of patients, inter-instrument and inter-rater variability, a relatively small evaluable patient sample size comprising predominantly Greek patients, and no uniform definition for “inadequate response” to aflibercept (based on the physician judgment).

Disclosure: This research was supported by Novartis Hellas, which was involved in the study design. Please see the original reference for a full list of disclosures.


Rouvas A, Datseris I, Androudi S, et al. A real-world, multicenter, 6-month prospective study in Greece of the effectiveness and safety of ranibizumab in patients with age-related macular degeneration who have inadequately responded to aflibercept: The “ELEVATE” study. Clin Ophthalmol. 2022;16(8):2579-2593. doi:10.2147/OPTH.S371036