Abstract:In the real-world setting, there is suboptimal compliance with treatments that require frequent administration and assessment visits. This undertreatment frequently has negative consequences in eye disease and carries a real risk to vision. For example, patients with glaucoma risk progression of visual loss even with a small number of missed doses, and patients with neovascular age-related degeneration (nAMD) who fail to attend a bi-monthly clinic appointment to receive an intravitreal anti-vascular endothelia… Show more
“…However, although found effective, these drugs have limitations, such as poor compliance, frequent dosing injections, and economic burden. Therefore, long-acting anti-VEGF agents that may prolong the dosing interval may help improve the efficacy and adherence [ 9 , 11 ].…”
Background
The current standard treatment for neovascular age-related macular degeneration (nAMD) involves intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. The aim of the present study was to compare the effectiveness and safety of two anti-VEGF drugs: brolucizumab and aflibercept, in treatment-naïve nAMD Indian patients over a period of 48 weeks.
Methods
A prospective, randomized, single-centre, single-blinded, two-arm comparative study was conducted between March 2021 and February 2022. Of the 114 patients, 56 received intravitreal injections of brolucizumab (6 mg/50 µL) while 58 received aflibercept (2 mg/50 µL). The patients received 03 initial loading doses at 4-week intervals of both the agents and then respective therapies were given as individualized pro re nata (PRN) regimen based on the signs of active macular neovascularization. The functional and anatomical outcomes measured were mean change in best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), presence of intraretinal fluid, subretinal fluid or subretinal hyper-reflective material. Furthermore, the average number of additional injections required after the loading doses, the injection-free interval and safety of both the drugs were also assessed.
Results
Brolucizumab was found to be non-inferior to aflibercept in terms of mean change in BCVA (−0.13 ± 0.21 logMAR vs. −0.10 ± 0.15 logMAR) and reduction in CMT (−112.59 ± 81.23 µm vs. −86.38 ± 71.82 µm). The percentage of eyes with IRF and SHRM was comparable between both the groups while fewer eyes treated with brolucizumab indicated SRF presence than aflibercept after the loading doses. These beneficial effects of brolucizumab were observed with significant (p < 0.0001) lesser number of injections (1.8 ± 1.1 vs. 3.8 ± 1.5) from week 12 to week 48. Moreover, the probability of no injections after the loading doses was significantly higher with brolucizumab compared to aflibercept indicating prolonged injection-free intervals. The average ocular side effects were comparable in the two groups. One adverse event of severe vitritis requiring treatment with oral steroids occurred in Brolucizumab group, while no such event occurred in Aflibercept group.
Conclusion
The results of the present study suggest non-inferiority of brolucizumab PRN regimen to aflibercept PRN regimen in treatment naïve nAMD Indian patients while achieving longer inter-injection intervals.
Trial registration Clinical Trial Registration of India (CTRI/2021/06/034415). Registered 03 March, 2021, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=54328&EncHid=&userName =
“…However, although found effective, these drugs have limitations, such as poor compliance, frequent dosing injections, and economic burden. Therefore, long-acting anti-VEGF agents that may prolong the dosing interval may help improve the efficacy and adherence [ 9 , 11 ].…”
Background
The current standard treatment for neovascular age-related macular degeneration (nAMD) involves intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. The aim of the present study was to compare the effectiveness and safety of two anti-VEGF drugs: brolucizumab and aflibercept, in treatment-naïve nAMD Indian patients over a period of 48 weeks.
Methods
A prospective, randomized, single-centre, single-blinded, two-arm comparative study was conducted between March 2021 and February 2022. Of the 114 patients, 56 received intravitreal injections of brolucizumab (6 mg/50 µL) while 58 received aflibercept (2 mg/50 µL). The patients received 03 initial loading doses at 4-week intervals of both the agents and then respective therapies were given as individualized pro re nata (PRN) regimen based on the signs of active macular neovascularization. The functional and anatomical outcomes measured were mean change in best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), presence of intraretinal fluid, subretinal fluid or subretinal hyper-reflective material. Furthermore, the average number of additional injections required after the loading doses, the injection-free interval and safety of both the drugs were also assessed.
Results
Brolucizumab was found to be non-inferior to aflibercept in terms of mean change in BCVA (−0.13 ± 0.21 logMAR vs. −0.10 ± 0.15 logMAR) and reduction in CMT (−112.59 ± 81.23 µm vs. −86.38 ± 71.82 µm). The percentage of eyes with IRF and SHRM was comparable between both the groups while fewer eyes treated with brolucizumab indicated SRF presence than aflibercept after the loading doses. These beneficial effects of brolucizumab were observed with significant (p < 0.0001) lesser number of injections (1.8 ± 1.1 vs. 3.8 ± 1.5) from week 12 to week 48. Moreover, the probability of no injections after the loading doses was significantly higher with brolucizumab compared to aflibercept indicating prolonged injection-free intervals. The average ocular side effects were comparable in the two groups. One adverse event of severe vitritis requiring treatment with oral steroids occurred in Brolucizumab group, while no such event occurred in Aflibercept group.
Conclusion
The results of the present study suggest non-inferiority of brolucizumab PRN regimen to aflibercept PRN regimen in treatment naïve nAMD Indian patients while achieving longer inter-injection intervals.
Trial registration Clinical Trial Registration of India (CTRI/2021/06/034415). Registered 03 March, 2021, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=54328&EncHid=&userName =
“…Several clinical trials are ongoing, such as a study for evaluation of the efficacy and safety study of ENV 515 for the treatment of ocular hypertension (NCT02371746) and glaucoma. AR-13503 (NCT03835884) and AR-1105 (NCT03739593) were designed as intravitreal implants for treating AMD and diabetic macular edema [ 3 , 240 ]. Several other under clinical trial ophthalmic nanomedicines, include Taxol (Paclitaxel albumin-stabilized nanoparticle formulation), which has done phase II clinical trial for treating intraocular melanoma [ 241 ]; GB-102 (Sunitinib malate), in phase I clinical trial for AMD therapy [ 242 ]; KPI-121 (1% and 0.25% loteprednol etabonate), is currently in phase III clinical trial for the treatment of ocular infection, irritation and inflammation [ 243 ] and OCS-01 (dexamethasone cylcodextrin) has done phase II clinical trial for treating eye inflammation and pain [ 244 ] (Table 2 ).…”
Section: Fda Approved and Under Clinical Trial Nanomedicine For Ocula...mentioning
Ocular drug delivery is one of the most challenging endeavors among the various available drug delivery systems. Despite having suitable drugs for the treatment of ophthalmic disease, we have not yet succeeded in achieving a proper drug delivery approach with the least adverse effects. Nanotechnology offers great opportunities to overwhelm the restrictions of common ocular delivery systems, including low therapeutic effects and adverse effects because of invasive surgery or systemic exposure. The present review is dedicated to highlighting and updating the recent achievements of nano-based technologies for ocular disease diagnosis and treatment. While further effort remains, the progress illustrated here might pave the way to new and very useful ocular nanomedicines.
“…Dies kann eine Krankheitsaktivität nach sich ziehen, die durch Neuauftreten oder eine relevante Zunahme der retinalen Flüssigkeiten und Visusverluste gekennzeichnet ist. Auch wenn sich erste Anti-VEGF-Therapien in der nAMD-Behandlung bereits als wirksam erwiesen haben, hat ihre zeitlich begrenzte Wirkdauer bislang häufige Behandlungen und Kontrollen erfordert, was zu einer hohen Behandlungslast der Patient*innen führen kann [15,16]. Dies zeigte sich in einer retrospektiven Studie a aus Frankreich, in der innerhalb des Beobachtungszeitraums von 5 Jahren etwa die Hälfte der Patient*innen ihre Behandlung unter anderem aufgrund von subjektiver Unzufriedenheit mit dem Nutzen der Therapie und der Belastung durch häufige Visiten abbrachen [17].…”
Section: Behandlungslast Trotz Flexiblerer Schemata Weiterhin Hochunclassified
“…Dies zeigte sich in einer retrospektiven Studie a aus Frankreich, in der innerhalb des Beobachtungszeitraums von 5 Jahren etwa die Hälfte der Patient*innen ihre Behandlung unter anderem aufgrund von subjektiver Unzufriedenheit mit dem Nutzen der Therapie und der Belastung durch häufige Visiten abbrachen [17]. Die Ergebnisse verdeutlichen den Bedarf an wirksamen Therapien, die retinale Flüssigkeiten stark und vor allem langanhaltend reduzieren und dadurch potenziell längere Injek tionsintervalle ermöglichen [15,16].…”
Section: Behandlungslast Trotz Flexiblerer Schemata Weiterhin Hochunclassified
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