Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration

Li, Emily; Donati, Simone; Lindsley, Kristina; Krzystolik, Magdalena G.; Virgili, Gianni

doi:10.1002/14651858.cd012208.pub2

Cited by 75 publications

(73 citation statements)

References 112 publications

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“…The management of these disorders over the past 16 years has been revolutionized by the rapid, widespread adoption of intravitreal antivascular endothelial growth factor (anti-VEGF) therapy [8]. Four drugs (pegaptanib sodium (Macugen Ò , Eyetech/OSI Pharmaceuticals, New York, NY, USA), ranibizumab (Lucentis Ò ; Genentech, South San Francisco, CA/Roche, Basel, Switzerland), aflibercept (Eylea Ò , Regeneron, Tarrytown, NY), and brolucizumab (Beovu Ò ; Novartis, Basel, Switzerland)) [9][10][11] have been approved by the US Food and Drug Administration (FDA) for intraocular use while bevacizumab (Avastin Ò ; Genentech, South San Francisco, CA/Roche, Basel, Switzerland) is used off-label [12].…”

Section: Introductionmentioning

confidence: 99%

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases

Chakraborty¹,

Stewart

Sheth

et al. 2021

Ophthalmol Ther

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Introduction To assess the safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab ® (Intas Pharmaceuticals, Ahmedabad, India) in chorioretinal disorders under real-world conditions. Methods This was a multicenter, retrospective chart review which included patients from 15 centers receiving intravitreal Razumab (IVRz) injections from 2016 to 2020. Patient demographics, ocular examination data, and detailed safety information regarding serious adverse events (SAE) or serious adverse drug reactions (sADR), and non-serious AEs (nsAE) or non-serious ADRs (nsADR) occurring within 1 month of IVRz injections were compiled. Results A total of 6404 eyes of 6404 patients received 9406 IVRz injections [mean (± SD) = 1.49 (± 0.63)] during 4.25 years. Adverse events were reported after 1978 injections (21.03%): 64.16% nsAE, 32.96% nsADR, 2.37% sADR, and 0.51% SAE. The most frequent adverse events were subconjunctival hemorrhage (8.2% of total injections), transient blurring of vision (6.5% of total injections), and mild ocular pain (5.27% of total injections). Serious ocular (31 cases with retinal pigment epithelial tears [0.33%], two cases of non-infectious vitritis [0.02%], and one case of endophthalmitis [0.01%]) and systemic (seven patients with non-fatal myocardial infarction [0.12%] and six patients with non-fatal cerebrovascular accident [0.09%]) adverse events were infrequent. Conclusion The study reports the largest pooled safety data on IVRz use in a real-world scenario. The results did not raise any new ocular or systemic safety concerns for the biosimilar agent, with the incidence and spectrum of adverse reactions similar to those reported with other anti-vascular endothelial growth factor (anti-VEGF) drugs. The real-world evidence suggests that IVRz is a safe anti-VEGF agent in the management of chorioretinal disorders. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00345-2.

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Section: Introductionmentioning

confidence: 99%

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases

Chakraborty¹,

Stewart

Sheth

et al. 2021

Ophthalmol Ther

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“…Reaching the drug targets in the retina requires effective drug delivery techniques ( 2 , 3 ), and in the case of AMD, therapeutic levels of anti-VEGF proteins such as bevacizumab, ranibizumab, and aflibercept in the retina can only be achieved via intravitreal (IVT) injection ( 4 – 7 ). However, IVT injections are invasive, costly and need to be repeated monthly or bimonthly ( 6 , 8 ). Longer acting and retina-targeting dosage forms are an important goal in current retinal drug development ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Extended Pharmacokinetic Model of the Intravitreal Injections of Macromolecules in Rabbits. Part 2: Parameter Estimation Based on Concentration Dynamics in the Vitreous, Retina, and Aqueous Humor

et al. 2020

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Purpose To estimate the diffusion coefficients of an IgG antibody (150 kDa) and its antigen-binding fragment (Fab; 50 kDa) in the neural retina (Dret) and the combined retinal pigment epithelium-choroid (DRPE-cho) with a 3-dimensional (3D) ocular pharmacokinetic (PK) model of the rabbit eye. Methods Vitreous, retina, and aqueous humor concentrations of IgG and Fab after intravitreal injection in rabbits were taken from Gadkar et al. (2015). A least-squares method was used to estimate Dret and DRPE-cho with the 3D finite element model where mass transport was defined with diffusion and convection. Different intraocular pressures (IOP), initial distribution volumes (Vinit), and neural retina/vitreous partition coefficients (Kret/vit) were tested. Sensitivity analysis was performed for the final model. Results With the final IgG model (IOP 10.1 Torr, Vinit 400 μl, Kret/vit 0.5), the estimated Dret and DRPE-cho were 36.8 × 10−9 cm2s−1 and 4.11 × 10−9 cm2s−1, respectively, and 76% of the dose was eliminated via the anterior chamber. Modeling of Fab revealed that a physiological model parameter “aqueous humor formation rate” sets constraints that need to be considered in the parameter estimation. Conclusions This study extends the use of 3D ocular PK models for parameter estimation using simultaneously macromolecule concentrations in three ocular tissues.

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“…[ 3 ] The recombinant anti-VEGF drugs bevacizumab (Avastin®; Genentech, S. San Francisco, CA/Roche, Basel, Switzerland), ranibizumab (Lucentis®; Genentech, S. San Francisco, CA/Roche, Basel, Switzerland), aflibercept (Eylea®, Regeneron, Tarrytown, NY), and brolucizumab (Beovu®; Novartis, Basel, Switzerland) are used widely throughout the world for management of various chorioretinal disorders. [ 4 5 6 ] Ranibizumab, aflibercept, and brolucizumab are approved by the US Food and Drug Administration (FDA) for the management of retinal conditions,[ 4 5 6 ] while bevacizumab, which is approved for the treatment of several advanced solid malignancies, is used off-label by ophthalmologists. [ 7 ]…”

mentioning

confidence: 99%

Visual outcomes, safety profile and morphometric response of optical coherence tomography biomarkers to ranibizumab biosimilar treatment in neovascular age-related macular degeneration: Real-world evidence

Kelkar

Bolisetty

et al. 2021

Indian J Ophthalmol

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Purpose: The aim of this study was to evaluate the safety, efficacy, and morphological response of intravitreal ranibizumab biosimilar (Razumab) in neovascular age-related macular degeneration (n-AMD) up to 12 weeks. Methods: Retrospective analysis of 20 eyes of n-AMD receiving 4 weekly intravitreal Razumab. Main outcome measures were mean change in best-corrected visual acuity (BCVA), intraretinal-fluid (IRF), subretinal-fluid (SRF), central-subfield thickness (CSFT), maximum central-retinal thickness (CRT), and dimensions of pigment epithelial detachment (PED) from baseline to weeks 4, 8 and 12. Results: Improvement in BCVA was seen at all visits, although not significantly (4 weeks: P = 0.18; 8 weeks: P = 0.4; 12 weeks: P = 0. 06). At 12 weeks, 90% of eyes either maintained or had an improvement in BCVA, with 40% of them showing an improvement of ≥3-lines and only 5% of them losing ≥3-lines of visual acuity. The median PED height and PED width reduced by 20.5 µm ( P = 0.03) and 557.5 µm ( P = 0.14), respectively, along with a mean reduction of 57.26 µmin CSFT ( P < 0.001) and 44.15 µm in CRT ( P = 0.004), respectively, at 12 weeks. On qualitative analysis, resolution of SRF and IRF was observed in 45% and 25% of eyes ‘ at 12 weeks. There were no serious ocular or systemic side effects identified. Conclusion: In real-world scenario, Razumab is an efficacious and economical anti-vascular endothelial growth factor (anti-VEGF) agent for optimal management of n-AMD. The therapeutic outcomes demonstrated reasonable stabilization and improvement in visual acuity, favorable anatomical outcomes pertaining to OCT-biomarkers with an acceptable safety profile.

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Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration

Abstract: Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration.

Cited by 75 publications

References 112 publications

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases

Extended Pharmacokinetic Model of the Intravitreal Injections of Macromolecules in Rabbits. Part 2: Parameter Estimation Based on Concentration Dynamics in the Vitreous, Retina, and Aqueous Humor

Visual outcomes, safety profile and morphometric response of optical coherence tomography biomarkers to ranibizumab biosimilar treatment in neovascular age-related macular degeneration: Real-world evidence

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