Brolucizumab Versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized Trial

Dugel, Pravin U.; Jaffe, Glenn J.; Sallstig, Peter; Warburton, James; Weichselberger, Andreas; Wieland, Mark R.; Singerman, Lawrence J.

doi:10.1016/j.ophtha.2017.03.057

Cited by 199 publications

(177 citation statements)

References 6 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…By binding free circulating VEGF or its receptors, these inhibitors prevent neovascularization. New anti-VEGF agents including brolucizumab [75], conbercept [76], designed ankyrin repeat protein (DARPin) [77] and sFLT01 [78] are currently under investigation. Despite significant visual improvements in patients with AMD since the availability of new drugs, challenges in AMD treatment are still present.…”

Section: Discussionmentioning

confidence: 99%

Exploring the cross talk between ER stress and inflammation in age-related macular degeneration

2017

View full text Add to dashboard Cite

Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER) stress is implicated in the development and progression of age-related macular degeneration (AMD), a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploring the cross talk between ER stress and inflammation in age-related macular degeneration

2017

View full text Add to dashboard Cite

show abstract

“…This interpretation could also explain the brolucizumab trial result that about 50% of neovascular AMD eyes were maintained on q12 week dosing with 6 mg brolucizumab throughout the study period. 29 There were several limitations to our study. First, it was an experiment on animals involving rabbit eyes.…”

Section: Discussionmentioning

confidence: 93%

“…It is estimated that 6 mg of brolucizumab equals about 12 times of the condensed concentration of 2.0 mg of aflibercept, and 22 times of 0.5 mg of ranibizumab. Recent clinical studies by Holz et al 28 and Dugel et al 29 pointed out that anatomic and visual improvements after administration of 6 mg of brolucizumab were comparable with those after administration of 2 mg of aflibercept, and a lesser number of injections could be administered in the 12-week treatment cycle. Overall, if ranibizumab is more concentrated as a 10-fold dose, like in our present experiment rather than just a four-fold dose as used in previous studies, we could argue that injecting a higher dose of ranibizumab might be beneficial for a longer duration.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Intraocular Pharmacokinetics of 10-fold Intravitreal Ranibizumab Injection Dose in Rabbits

Kim

Park

Lee

et al. 2020

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

Purpose:To investigate intraocular pharmacokinetics of 10-fold dose of intravitreally injected ranibizumab compared with the conventional dose in an experimental model. Methods:Ranibizumab 30 μL at 10 mg/mL (conventional) and 100 mg/mL (10-fold) doses was injected separately into each eye of 28 rabbits. Ranibizumab concentrations in the aqueous humor, vitreous, and retina were estimated at each time period after injection, using enzyme-linked immunosorbent assay. The pharmacokinetic properties of ranibizumab were determined using a one-compartment model in all three ocular tissues. The time-concentration profile and predictive trends were plotted to determine drug efficacy in the retina.Results: Maximum concentrations after conventional and 10-fold dosing were observed in the retina at 1 and 4 days after injection, respectively. The half-life of ranibizumab after conventional and 10-fold dosing did not differ in the anterior chamber and vitreous, whereas the half-life was prolonged approximately twice with the 10-fold dose in the retina (36.74 h vs. 76.85 h) and serum (91.93 h vs. 179.01 h). Similarly, the estimated time for ranibizumab concentration in the retina over 27 ng/mL (minimum effective concentration of ranibizumab) was prolonged approximately twice with the 10-fold dose (1315 h [55 days] vs. 2393 h [100 days]). No adverse effects were observed in either group. Conclusions:The retinal half-life and concentration of ranibizumab in rabbit eyes were increased approximately twice after a 10-fold dose compared with the conventional dose. This finding indicates a possibility to lengthen the injection interval to improve the efficacy of ranibizumab in human eyes.Translational Relevance: Our results highlight the potential for clinical application of a high-dose (10-fold) of anti-VEGF agents to prolong the intravitreal injection intervals, simultaneously improving the drug efficacy.

show abstract

“…Brolucizumab was found as good as if not better than aflibercept in a phase III clinical trial. 327 Cryopyrin-associated periodic syndromes (including familial cold auto-inflammatory syndrome and Muckle-Wells syndrome); tumor necrosis factor receptor-associated periodic syndrome (TRAPS); hyperimmunoglobulin D Syndrome (HIDS)/mevalonate kinase deficiency and familial Mediterranean fever (FMF) may also respond to canakinumab. 328…”

Section: Other Clinical Disordersmentioning

confidence: 99%

Passive Monoclonal and Polyclonal Antibody Therapies

Pelletier¹,

Mukhtar²

2020

Immunologic Concepts in Transfusion Medicine

View full text Add to dashboard Cite

Brolucizumab Versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized Trial

Cited by 199 publications

References 6 publications

Exploring the cross talk between ER stress and inflammation in age-related macular degeneration

Exploring the cross talk between ER stress and inflammation in age-related macular degeneration

Intraocular Pharmacokinetics of 10-fold Intravitreal Ranibizumab Injection Dose in Rabbits

Passive Monoclonal and Polyclonal Antibody Therapies

Contact Info

Product

Resources

About