Author: Elisabet Granstam (Sweden)
Co-authors: Kersti Sjövall, Sandra Aurell, Anna Paul, Mats Rosén
Purpose
Wet age-related macular degeneration (wet AMD) is the leading cause of severe visual impairment in the elderly population of the western world. Wet AMD is treated with intravitreal injections of anti-VEGF-agents. Currently, there are three anti-VEGF agents approved for treatment of wet AMD: ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab is used off-label at a much lower cost. At the Department of Ophthalmology at the County Hospital of Vastmanland Sweden, treatment for wet AMD is given according to a treat-and-extend protocol using aflibercept, with the aim at increasing treatment intervals up to 14 weeks. However, there is a subset of eyes with chronic severe and highly active wet AMD in need of intense treatment with 4-weekly injections of anti-VEGF agent over several years. In an attempt to reduce drug-related costs at the department, we decided to switch anti-VEGF agent from aflibercept to bevacizumab in this subset of eyes beginning on January 1, 2020. A re-switch back to aflibercept was allowed in case of reduction in visual acuity, increase in macular edema or both. The aim of the present study was to evaluate the clinical outcomes of the switch of anti-VEGF agents and investigate the frequency of re-switch.
Setting/Venue
Retrospective cohort study using real-world data from the Department of Ophthalmology at the County Hospital of Vastmanland, Sweden. The study was approved by the Swedish Ethical Review Authority (2021-00247) and was performed in adherence with the tenets of the Declaration of Helsinki.
Methods
Data from the Swedish Macular Register (SMR), electronic patient charts and imaging data (optical coherence tomography, OCT) from OCT 2000, Topcon were used. From the SMR, eyes with wet AMD on chronic 4-weekly anti-VEGF treatment for at least 12 months which had been switched from aflibercept to bevacizumab were identified. Follow-up for 12 months after the switch to bevacizumab was required for inclusion in the study. Main outcome measure was frequency of re-switch from bevacizumab to aflibercept over 12 months. The following data were collected: visual acuity (VA; ETDRS letters), central retinal thickness (CRT; µm), presence of intraretinal- (IRF)- subretinal- (SRF) and sub-RPE fluid (proportion of eyes: %) at the time of switch and at 12 months as well as number of anti-VEGF-treatments over 12 months. In case of re-switch to aflibercept, number of bevacizumab injections given at the time of re-switch and reasons for re-switch were collected. Statistical analysis was performed using SPSS (IBM). Mean and standard deviations (SD) are presented
Results
In total, 75 eyes were included. Mean age at the time of switch was 78.8 (SD 7.0) and 59% of patients were female. At inclusion, eyes had been on anti-VEGF-treatment for 4.5 (2.7) years. VA was ETDRS 66 (12) at treatment start and 68 (15) at switch. Proportions of eyes with IRF, SRF and sub-RPE fluid were 81%, 63%, and 32%, respectively and CRT was 221 (38) µm at switch. During the 12 months follow-up, a re-switch from bevacizumab to aflibercept was performed in 46 eyes (62%). The re-switch was due to increased macular edema in 34/46 (74%) eyes, reduced VA in 30/46 (65%) eyes or combination of these in 21/46 (46%) eyes. Three eyes were re-switched due to intraocular inflammation. In 22% of eyes, the re-switch was performed at the follow-up after the first bevacizumab injection and in 69% of eyes after a maximum of four bevacizumab injections. At 12-month follow-up, mean VA was ETDRS 66 (18) for all eyes. IRF, SRF and sub-RPE fluid was detected in 80%, 69%, and 37% of eyes, respectively and CRT was 227 (38) µm. Eyes were treated with a total 12 (2) anti-VEGF-injections over 12 months.
Conlusions
In this study, we found that almost 40% of eyes with chronic, severe, highly active wet AMD on 4-weekly anti-VEGF treatment had stable vision and unchanged macular status on OCT over 12 months following switch from aflibercept to bevacizumab. On the other hand, worsening of the disease occurred in 62% of eyes after the switch to bevacizumab. In a majority of these eyes, the worsening occurred early after switch of anti-VEGF agent. In 2/3 of eyes, the deterioration was detected within four bevacizumab injections. After re-switch to aflibercept, VA and macular edema on OCT recovered. Our findings indicate that a subset of eyes on chronic 4-weekly anti-VEGF-treatment remain stable after switch to bevacizumab. In case of worsening of VA and OCT after switch to bevacizumab, we found that it occurred early after change of anti-VEGF agent. If switch from aflibercept to bevacizumab is considered, close surveillance of VA and OCT is necessary, especially during the first 6 months. Re-switch to aflibercept should be performed promptly if deterioration is detected to avoid irreversible visual loss.
Financial Disclosure
Elisabet Granstam: Novartis (consultant, advisory board), Bayer (advisory board), Allergan (advisory board, lecturing fee) Kersti Sjövall: Novartis (advisory board), Bayer (advisory board) Sandra Aurell: no financial relations Anna Paul: no financial relations Mats Rosén: no financial relations
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