Comparative efficacy and safety of anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: systematic review and Bayesian network meta-analysis

Lu, Yao; Zhao, Jiaqi; Wang, Jianchao; Feng, Zhong‐Ping; Yao, Liang; Zhang, Xiaohui

doi:10.1177/2040622320953349

Cited by 13 publications

(9 citation statements)

References 67 publications

(87 reference statements)

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“…Changes in the strategy of anti-VEGF regimen in real-life settings have conducted to the application of treat-and-extend approaches rather than pro re nata (PRN) with subsequent reduced burden and similar outcomes to the monthly administration regimens applied in registrative trials [ 27 , 28 ]. Recently, a Bayesian network meta-analysis on neovascular AMD concluded that the treat-and-extend regimen proved to be the most effective approach for each anti-VEGF drug available [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-VEGF therapies for age-related macular degeneration: a powerful tactical gear or a blunt weapon? The choice is ours

Lanzetta

2021

Graefes Arch Clin Exp Ophthalmol

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Purpose Blindness and vision loss are still frequent disabilities associated with a relevant impact on health care and quality of life, and a high economic burden. Supranational programs established by the World Health Organization (WHO), International Agency for the Prevention of Blindness (IAPB), and World Health Assembly (WHA) aim at reducing avoidable visual impairment. Age-related macular degeneration (AMD), diabetic retinopathy (DR), and other retinal diseases are well known causes of visual disability. Since more than a decade, intravitreal agents are available for the treatment of these diseases. The aim of this study is to review whether pharmacotherapy with anti-vascular endothelial growth factor (VEGF) drugs has led to a decrease in the prevalence of blindness with emphasis on AMD and different countries. A brief analysis of other factors correlated to changes in the rate of blindness is also presented. Methods PubMed and Scopus web platforms were used to identify relevant studies on epidemiology of blindness and vision impairment, the influence of intravitreal therapies, and the existence of different vision care models. Additional data and material was searched in web internet accessed by the web browser Firefox. Results Age-standardized prevalence of blindness secondary to AMD has started to decline as testified by a number of studies in different countries. This is due to the adoption of anti-VEGF therapy and its adequate management. The frequency of treatment and regimens applied are indirect signs of successful treatment. Local rules and regulations may represent an obstacle. Conclusions This review shows that by implementing existing health care systems and dispensing adequate therapies in the field of retinal diseases, the prevalence of blindness due to these conditions can decline.

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Section: Discussionmentioning

confidence: 99%

Anti-VEGF therapies for age-related macular degeneration: a powerful tactical gear or a blunt weapon? The choice is ours

Lanzetta

2021

Graefes Arch Clin Exp Ophthalmol

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“…Pegaptanib, ranibizumab 0.3 mg, and aflibercept 0.5 mg have been proven to have poor efficacy and are not recommended. Therefore, it was unnecessary to include drugs and dosagesthat are not recommended, and it was erroneous to merge different dosages into one group, such as merging 0.3 and 0.5 mg ranibizumab and merging 0.5 and 2 mg aflibercept, which might lead to inaccurate data and high heterogeneity (Ye et al, 2020). Similarly, the indiscriminate and non-standard merger of different therapeutic frequencies caused inaccurate results, such as combining different PRN regimens (Ye et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…The errors of study selection and data collection would cause a serious mistake. Conbercept was included in the previous study (Ye et al, 2020), which actually could not be included due to the lack of RCTs available to connect to the node graph of the network due to the lack of true placebo groups in the PHOENIX and AURORA studies to form closed loops for the network and the reassigned regimen (Li et al, 2014;Liu et al, 2019). Similarly, Dugel's study (2017) of brolucizumab was included in the previous study non-standardly due to different therapeutic frequencies and week 40 available data only (Dugel et al, 2017;Ye et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Conbercept was included in the previous study (Ye et al, 2020), which actually could not be included due to the lack of RCTs available to connect to the node graph of the network due to the lack of true placebo groups in the PHOENIX and AURORA studies to form closed loops for the network and the reassigned regimen (Li et al, 2014;Liu et al, 2019). Similarly, Dugel's study (2017) of brolucizumab was included in the previous study non-standardly due to different therapeutic frequencies and week 40 available data only (Dugel et al, 2017;Ye et al, 2020). Third, to maximize the clinical significance and acquire evidence with as high quality as possible for our study, we included anti-VEGF monotherapies that were recommended by current guidelines only, without various combination treatments, such as NSAIDs, triamcinolone, and radiation therapy, which might have no value for the current clinical applications (Zhao et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…However, it is difficult to acquire comparative efficacy and safety profiles from current trials due to the lack of head-to-head trials. Meanwhile, several problems in published meta-analyses, such as indiscriminate merger, inaccurate dosage distinction, and redundancy inclusion, remain to be resolved with more precise analysis (Ye et al, 2020;Zhao et al, 2021). Here, we report comprehensive monotherapy-based mixed treatment comparisons (Bayesian network meta-analysis) of efficacy (visual acuity and anatomical structure), safety, and therapeutic frequency in patients receiving anti-VEGF monotherapy, which can overcome the shortage of direct comparison trials and combine direct and indirect data to compare two or more interventions simultaneously to identify the utilization and prioritization of anti-VEGF monotherapies in nAMD patients.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Anti–Vascular Endothelial Growth Factor Monotherapies for Neovascular Age-Related Macular Degeneration: A Mixed Treatment Comparison

Zhang¹,

Gao²,

Li³

et al. 2021

Front. Pharmacol.

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Background: We aimed to evaluate the comparative efficacy and safety of anti–vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD).Methods: Eligible studies included randomized controlled trials comparing the recommended anti-VEGF agents (ranibizumab, bevacizumab, aflibercept, brolucizumab, and conbercept) under various therapeutic regimens. Outcomes of interest included the mean change in best-corrected visual acuity (BCVA), serious adverse events, the proportion of patients who gained ≥15 letters or lost <15 letters in BCVA, the mean change in central retinal thickness, and the number of injections within 12 months.Results: Twenty-seven trials including 10,484 participants and eighteen treatments were identified in the network meta-analysis. The aflibercept 2 mg bimonthly, ranibizumab 0.5 mg T&E, and brolucizumab 6 mg q12w/q8w regimens had better visual efficacy. Brolucizumab had absolute superiority in anatomical outcomes and a relative advantage of safety, as well as good performance of aflibercept 2 mg T&E. The proactive regimens had slightly better efficacy but a slightly increased number of injections versus the reactive regimen. Bevacizumab had a statistically non-significant trend toward a lower degree of efficacy and safety.Conclusion: The visual efficacy of four individual anti-VEGF drugs is comparable. Several statistically significant differences were observed considering special anti-VEGF regimens, suggesting that brolucizumab 6 mg q12w/q8w, aflibercept 2 mg bimonthly or T&E, and ranibizumab 0.5 mg T&E are the ideal anti-VEGF regimens for nAMD patients. In the current landscape, based on the premise of equivalent efficacy and safety, the optimal choice of anti-VEGF monotherapies seems mandatory to obtain maximal benefit.

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Comparative Efficacy of Brolucizumab in the Treatment of Neovascular Age-Related Macular Degeneration: A Systematic Literature Review and Network Meta-Analysis

Finger

Dennis²,

Freitas

et al. 2022

Adv Ther

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Introduction A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) at 1 and 2 years, and overall safety and injection frequency of each treatment. Methods An SLR identifying randomized controlled trials (RCTs) published before June 2021 according to a pre-specified protocol was followed by a Bayesian NMA to compare brolucizumab (6 mg q12w/q8w) against sham and all relevant anti-VEGF regimens. Pooled mean injection frequency, serious adverse ocular events, and discontinuation rates were estimated for each treatment regimen. Results Nineteen RCTs were included in NMA base-case analysis. Brolucizumab (6 mg q12w/q8w) with loading-phase (LP) demonstrated superior best-corrected visual acuity (BCVA) gains to sham both at year 1 (mean difference 16.8 [95%CrI 13.3, 20.4]) and year 2 (mean difference 21.2 [95%CrI 17.4, 25.0]) and was comparable to other anti-VEGFs. Brolucizumab (6 mg q12w/q8w) also showed superior retinal thickness reduction to most comparators including ranibizumab (0.5 mg q4w; year 1 mean difference − 50.1 [95%CrI − 70.3, − 29.8]; year 2 mean difference − 49.5 [95%CrI − 70.8, − 28.6]), aflibercept (2 mg q8w; year 1 mean difference − 39.7 [95%CrI − 52.9, − 26.4]; year 2 mean difference − 35.0 [95%CrI − 49.1, − 21.4]), and faricimab (6 mg q16w/q8w; year 1 mean difference − 27.6 [95%CrI − 42.3, − 12.8]). Brolucizumab (6 mg q12w/q8w) showed similar rates of treatment discontinuation and serious and overall adverse events (both years). At year 2, pooled annualized injection frequency was lowest for brolucizumab (6 mg q12w/q8w) and highest for ranibizumab (0.5 mg q4w) at 5.7 and 11.5 injections annually, respectively. Conclusion Among all licensed anti-VEGF treatments, brolucizumab showed superior reduction in retinal thickness and comparable BCVA gains and discontinuation rates, despite having the lowest injection frequency. The current study provides the most up-to-date, robust comparison of treatments for nAMD. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02193-3.

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Comparative efficacy and safety of anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: systematic review and Bayesian network meta-analysis

Cited by 13 publications

References 67 publications

Anti-VEGF therapies for age-related macular degeneration: a powerful tactical gear or a blunt weapon? The choice is ours

Anti-VEGF therapies for age-related macular degeneration: a powerful tactical gear or a blunt weapon? The choice is ours

Efficacy and Safety of Anti–Vascular Endothelial Growth Factor Monotherapies for Neovascular Age-Related Macular Degeneration: A Mixed Treatment Comparison

Comparative Efficacy of Brolucizumab in the Treatment of Neovascular Age-Related Macular Degeneration: A Systematic Literature Review and Network Meta-Analysis

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