Systemic Pharmacokinetics and Pharmacodynamics of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab

Avery, Robert L.; Castellarin, Alessandro; Steinle, Nathan; Dhoot, Dilsher S.; Pieramici, Dante J.; See, Robert F.; Couvillion, Stephen; Nasir, Maʼan; Rabena, Melvin D.; Maia, Maurício; Everen, Sherri Van; Le, Kha; Hanley, William D.

doi:10.1097/iae.0000000000001493

Cited by 259 publications

(283 citation statements)

References 57 publications

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“…Zehetner et al [46] showed that IVB reduces serum VEGF levels for at least a month, while ranibizumab does not reduce serum VEGF levels significantly in adult patients treated for diabetic macular edema (DME) and age-related macular degeneration (ARMD). Similarly, Avery et al [47] revealed that bevacizumab decreases serum free VEGF levels more than ranibizumab in adult patients treated for DME, ARMD, and retinal vein occlusion. In a recent study, Wu et al [48] investigated the effects of IVB and IVR on serum VEGF levels in patients with type 1 ROP.…”

Section: Discussionmentioning

confidence: 94%

Comparison of Bevacizumab and Ranibizumab in the Treatment of Type 1 Retinopathy of Prematurity Affecting Zone 1

Kimyon

Mete²

2018

Ophthalmologica

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Purpose: To investigate the effects of bevacizumab and ranibizumab in the treatment of type 1 retinopathy of prematurity (ROP) affecting zone 1. Methods: Files of the patients who received intravitreal bevacizumab (IVB) or ranibizumab (IVR) treatment for ROP affecting zone 1 were evaluated retrospectively. Spherical equivalent (SE) and axial length (AXL) measurements were performed at 1 year of adjusted age. Results: Sixty-eight eyes of 37 patients were included in the study. All patients had initial disease regression but 6 patients (4 in the IVB, 2 in the IVR group) showed reactivation (p = 0.679). The number of eyes with incomplete vascularization were 15 and 12 in the IVB and IVR groups, respectively (p = 0.725). Mean AXL was 20.50 ± 0.99 mm in the IVB group and 19.30 ± 0.48 mm in the IVR group (p < 0.001). Mean SE was –1.49 ± 2.38 dpt in the IVB group and 0.98 ± 2.18 dpt in the IVR group (p < 0.001). Conclusion: Bevacizumab and ranibizumab showed similar effectiveness in the treatment of type 1 ROP affecting zone 1. The AXL was longer and SE was more myopic in eyes treated with IVB. This difference might be caused by the longer intravitreal half-life of bevacizumab than ranibizumab.

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Section: Discussionmentioning

confidence: 94%

Comparison of Bevacizumab and Ranibizumab in the Treatment of Type 1 Retinopathy of Prematurity Affecting Zone 1

Kimyon

Mete²

2018

Ophthalmologica

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“…The systemic effect of anti-VEGF agents has been a concern since these drugs became first-line therapy for several intraocular conditions, even though only small amounts of the anti-VEGF drugs are released from the eye into the systemic circulation [28, 30]. While intraocular VEGF is a critical mediator of angiogenesis involved in the pathogenesis of diseases such as nAMD, DME, and RVO (retinal vein occlusion), systemic VEGF acts as a vascular protective factor essential for maintaining the integrity and antithrombogenic properties of the endothelium [31].…”

Section: Discussionmentioning

confidence: 99%

Same-Day Bilateral Intravitreal Anti-Vascular Endothelial Growth Factor Injections: Experience of a Large Canadian Retina Center

et al. 2019

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Objective: To evaluate the outcomes and complications of bilateral same-day intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Methods: This is a single-center, retrospective study that included 524 eyes of 262 patients who received concomitant bilateral intravitreal anti-VEGF injections in 2016 at St. Michael’s Hospital, Toronto. If any of the patients were receiving simultaneous bilateral injections on a regular basis prior to 2016, data pertaining to previous injections were also reviewed. Everyone received bevacizumab, ranibizumab, or aflibercept in an office setting. Results: A total of 9,798 intravitreal anti-VEGF injections (4,899 bilateral injection sessions) were performed in 524 eyes of 262 patients. The average number of bilateral injection sessions per patient was 18.7 ± 14.1. Ranibizumab was the most commonly used anti-VEGF drug (83.8%). The incidence of endophthalmitis was 0.01%, and there were 2 episodes of acute intraocular inflammation among the 9,798 injections (0.02%). All 3 cases occurred after treatment with ranibizumab. There were 2 deaths (0.76%) due to nonvascular causes but no vascular related systemic adverse events were reported. Conclusions: Same-day bilateral intravitreal anti-VEGF injections present a low rate of complications and are well tolerated by patients. This safe practice may reduce the burden on the health-care system and on the patients.

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“…Interestingly, eyes that had more treatment before the switch were more likely to have greater visual improvement. Possible reasons for the significant anatomical and functional response seen with aflibercept may be due to its differing pharmacokinetic and pharmacodynamics properties and the greater disease activity in these patients . Aflibercept features a higher binding affinity to VEGF‐A and to additional growth factors released during angiogenesis such as VEGF‐B and PIGF, in contrast to inactivation of only VEGF‐A with bevacizumab and ranibizumab .…”

Section: Discussionmentioning

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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Systemic Pharmacokinetics and Pharmacodynamics of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab

Cited by 259 publications

References 57 publications

Comparison of Bevacizumab and Ranibizumab in the Treatment of Type 1 Retinopathy of Prematurity Affecting Zone 1

Comparison of Bevacizumab and Ranibizumab in the Treatment of Type 1 Retinopathy of Prematurity Affecting Zone 1

Same-Day Bilateral Intravitreal Anti-Vascular Endothelial Growth Factor Injections: Experience of a Large Canadian Retina Center

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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