Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

Spooner, Kimberly; Hong, Thomas; Wijeyakumar, Wijeyanthy; Chang, Andrew

doi:10.2147/opth.s125676

Cited by 53 publications

(40 citation statements)

References 62 publications

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“…The findings reported here are remarkably similar to the overall results of uncontrolled switching trials summarized in 2 meta-analyses. 9,13 Spooner et al 13 reported mean 1.11-and 0.63-letter gains at months 6 and 12, respectively, after switching from ranibizumab or bevacizumab to aflibercept. Neither change was significantly different from a 0-letter gain.…”

Section: Discussionmentioning

confidence: 99%

“…Meta-analyses examining numerous anti-VEGF switching studies have shown that most patients with nAMD who switch treatment from either ranibizumab or off-label bevacizumab to aflibercept demonstrate continued anatomic improvement with vision stabilization or limited visual improvement. 9,13 Although these benefits generally are attributed to the new anti-VEGF agent, limitations in study design preclude definitive conclusions regarding the cause of the improvement. Most of these studies do not include a comparator arm, and as a result, it is unclear if the benefits achieved are the result of the new anti-VEGF drug, the result of continuing anti-VEGF treatment for a longer duration, or something else.…”

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confidence: 99%

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Simulating an Anti–Vascular Endothelial Growth Factor Switch in Neovascular Age-Related Macular Degeneration

Zarbin

Tsuboi²,

Hill³

et al. 2019

Ophthalmology

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Purpose: A simulated switching study assessed the effects of continuing the same antievascular endothelial growth factor (VEGF) treatment among patients who typically are considered for a therapy switch. Post hoc analysis of data from HARBOR was undertaken. Patients with neovascular age-related macular degeneration who demonstrated a suboptimal response after 3 or 6 months of ranibizumab treatment were identified as switching candidates. Rather than switching, however, patients continued on ranibizumab treatment, and visual and anatomic outcomes from the point of the hypothetical switch were examined. Design: Post hoc analysis of the phase 3 HARBOR clinical trial. Participants: Patients were included in 3-and 6-month switcher analyses if they received 3 of 3 initial monthly ranibizumab doses and 5 of 6 initial monthly ranibizumab doses, respectively, and met all the following: 5-letter or fewer gain from baseline, best-corrected visual acuity (BCVA) 20/40 or worse, and intraretinal or subretinal fluid with central foveal thickness (CFT) equal to or greater than central subfield thickness. Methods: Patient data were examined at months 3 and 6 to identify those who met predetermined switching criteria. Best-corrected visual acuity and CFT were examined from the point at which switching criteria were met through months 6, 12, 18, and 24 of HARBOR and compared with those who did not meet the criteria. Main Outcome Measures: Outcome measures included mean BCVA and CFT change over time from the point (month 3 or 6) at which switching criteria were met. Results: By months 3 and 6, only 44 of 1059 patients (4.2%) and 37 of 769 patients (4.8%), respectively, met the inclusion criteria for hypothetical switching. Patients who met switching criteria at month 3 gained, on average, 5.3 letters from months 3 to 12 and 2.7 letters from months 3 to 24. Month 6 switchers gained, on average, 1.6 letters from months 6 to 12 and 1.8 letters from months 6 to 24. Both groups experienced significant CFT reductions over 24 months. Conclusions: Month 3 hypothetical switchers achieved vision and anatomic improvement while continuing their original ranibizumab treatment. Month 6 switcher outcomes replicated those commonly reported in published anti-VEGF switching studies: stable vision or nominal improvements in vision with continued substantial anatomic improvement.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Simulating an Anti–Vascular Endothelial Growth Factor Switch in Neovascular Age-Related Macular Degeneration

Zarbin

Tsuboi²,

Hill³

et al. 2019

Ophthalmology

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“…; Spooner et al. ). Few have assessed the efficacy for refractory cases of macular oedema in RVO (Konidaris et al.…”

Section: Introductionmentioning

confidence: 97%

A meta‐analysis of patients with treatment‐resistant macular oedema secondary to retinal vein occlusions following switching to aflibercept

Spooner

Hong²,

Bahrami

et al. 2018

Acta Ophthalmologica

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To systematically review anatomical and functional outcomes of switching therapy from bevacizumab and/or ranibizumab to aflibercept in patients with persistent macular oedema secondary to retinal vein occlusions (RVO). A systematic search of aflibercept for the treatment of persistent macular oedema secondary to branch and central RVO was performed in EMBASE, PubMed and Cochrane databases prior to June 2017. The main outcome variables described were best-corrected visual acuity (BCVA) and central macular thickness (CMT). All results were analysed and pooled using random-effects models with 95% confidence intervals (CI). Eight studies met the inclusion criteria with a total of 137 eyes, incorporating both branch and central RVO. Meta-analysis demonstrated a nonsignificant change in BCVA at 6 and 12 months following switch to aflibercept (4.40 letters, 95% CI: À3.10 to 11.90, p = 0.25 and 3.10 letters, 95% CI: À1.74 to 7.94, p = 0.21, respectively). Significant improvement in mean CMT was observed after switch to aflibercept at 6 (À256.00 lm, 95% CI: À318.00 to À194.00, p < 0.001) but not 12 months (À118.00 lm, 95% CI: À261.00 to 25.00, p = 0.11). Switching from bevacizumab/ranibizumab to aflibercept may improve persistent macular oedema secondary to RVO. However, there may be a limitation in the potential of visual recovery.

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“…It is possible that some eyes may respond better to one VEGF inhibitor than another, however few prospective studies have evaluated the effects of switching VEGF inhibitors in eyes with RVO . Switching studies have been reported in age related macular degeneration and diabetic macular oedema . However, there are few published prospective studies which examine the efficacy of switching anti‐VEGF agents in eyes with RVO …”

Section: Introductionmentioning

confidence: 99%

Prospective study of aflibercept for the treatment of persistent macular oedema secondary to retinal vein occlusions in eyes not responsive to long‐term treatment with bevacizumab or ranibizumab

Spooner

Fraser‐Bell

Hong³

et al. 2019

Clinical Exper Ophthalmology

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Importance: To examine the effect of switching from intravitreal bevacizumab or ranibizumab to aflibercept in eyes with persistent macular oedema due to retinal vein occlusion (RVO). Background: We report the results of a prospective interventional study on the effect of aflibercept 2 mg in eyes with persistent macular oedema after long-term treatment with bevacizumab or ranibizumab. Design: Non-randomized, prospective clinical trial. Participants: Eighteen eyes of eighteen patients were included.Methods: Eyes with persistent macular oedema despite a minimum of four previous intravitreal bevacizumab/ranibizumab injections were recruited into this 48-week trial. Three loading doses of intravitreal aflibercept were administered every 4-weeks, thereafter every 8-weeks until week 48. Main Outcome Measures: Mean change from baseline in best corrected visual acuity (BCVA) as measured by early treatment diabetic retinopathy score (ETDRS) and central macular thickness (CMT) as measured by spectral domain optical coherence tomography (SD-OCT) at 48 weeks. Results: Patients had received a mean of 40.0 ± 17.8 bevacizumab/ranibizumab intravitreal injections prior to switching to aflibercept. The mean number of previous injections administered in the 12-months preceding entry into the study was 10.2 ± 2.4. Mean vision change at week 48 was +21.1 ± 5.1 ETDRS letters in the BRVO group and +18.8 ± 5.9 letters at in the CRVO group (P < .001 for both groups). Mean decrease in CMT was 87.6 ± 48.8 μm and 191.0 ± 128.3 μm, in the BRVO and CRVO groups, respectively (P < .001). Using linear regression

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Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

Cited by 53 publications

References 62 publications

Simulating an Anti–Vascular Endothelial Growth Factor Switch in Neovascular Age-Related Macular Degeneration

Simulating an Anti–Vascular Endothelial Growth Factor Switch in Neovascular Age-Related Macular Degeneration

A meta‐analysis of patients with treatment‐resistant macular oedema secondary to retinal vein occlusions following switching to aflibercept

Prospective study of aflibercept for the treatment of persistent macular oedema secondary to retinal vein occlusions in eyes not responsive to long‐term treatment with bevacizumab or ranibizumab

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