Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Finger RP

PROVIDER: S-EPMC9309118 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Finger Robert P RP Dennis Natalie N Freitas Rita R Quenéchdu Arthur A Clemens Andreas A Karcher Helene H Souied Eric H EH

Advances in therapy 20220609 8

<h4>Introduction</h4>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.<h4>Methods</h4>An SLR identifying randomized controlled trials (RCTs) published before June 2021 according to a pre-specified prot ...[more]

PMID: 35678996

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Project description:ImportanceOutcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD).ObjectiveTo report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD.Design, setting, and participantsThis retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020.ExposuresTreatment with brolucizumab IVI, 6 mg.Main outcomes and measuresChange in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety.ResultsA total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, -2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) μm and was 269.8 (66.5) μm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision.Conclusions and relevanceIn this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.

Project description:ObjectiveTo give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD).DesignA systematic review and network meta-analysis.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials, and other clinical trial registries were searched up to 1 October 2019 to identify related randomised controlled trials (RCT) of different regimens of ranibizumab for nAMD. The primary efficacy outcome was the changes of best-corrected visual acuity (BCVA) at 1 year, the primary safety outcome was the incidence of severe ocular adverse events. Secondary outcomes such as changes of central retinal thickness (CRT) were evaluated. We estimated the standardised mean difference (SMD), ORs, 95% CIs, the surface under the cumulative ranking curves and the mean ranks for each outcome using network meta-analyses with random effects by Stata 14.0.ResultsWe identified 26 RCTs involving 10 821 patients with nAMD randomly assigned to 21 different therapeutic regimens of ranibizumab or sham treatment. Ranibizumab 0.5 mg (treat and extend, T&E) is most effective in terms of changes of BCVA (letters, SMD=21.41, 95% CI 19.86 to 22.95) and three or more lines of BCVA improvement (OR=2.83, 95% CI 1.27 to 4.38). However, it could not significantly reduce retreatment times compared with monthly injection (SMD=-0.94, 95% CI -2.26 to 0.39). Ranibizumab 0.5 mg (3+pro re nata)+non-steroidal anti-inflammatory drugs (NSAIDs) is most effective in reducing CRT and port delivery system of ranibizumab (100 mg/mL) could reduce the number of retreatment most significantly. All regimes have no more risk of severe ocular complications (including vitreous haemorrhage, rhegmatogenous retinal detachment, endophthalmitis, retinal tear and retinal pigment epithelium tear) or cardiocerebral vascular complications.ConclusionsRanibizumab 0.5 mg (T&E) is most effective in improving the visual outcome. The administration of topical NSAIDs could achieve additional efficacy in CRT reduction and visual improvement. Both interventions had acceptable risks of adverse events.

Project description:BackgroundAs a debilitating neurodegenerative disease, neovascular age-related macular degeneration (nAMD) accounts for more than 90% of severe visual loss or legal blindness among AMD patients. Anti-vascular endothelial growth factor (VEGF) had been applied widely in nAMD treatment. To date, debate regarding efficacy and safety still exists among different anti-VEGF regimens as management of nAMD. To provide substantial evidence for clinical nAMD treatment, this study ranks the priority of anti-VEGF regimens via Bayesian network meta-analysis (NMA), comparing data collected from randomized controlled trials (RCTs).MethodsWe searched PubMed Central, MEDLINE Ovid, Embase Ovid, ISRCTN, ICTRP and ClinicalTrials. gov from a database established until 1 April 2019 systematically for anti-VEGF regimens. Bayesian NMA with random-effect was conducted to compare efficacy and safety and rank priority of anti-VEGF regimens. The primary efficacy and safety outcomes were the proportion of patients gaining 15 or more letters, and the incidence of arterial thromboembolic (ATC) events. The effect measure is the standard mean difference (SMD), or the odds ratio (OR) with their 95% confidence interval (CI). The study protocol is registered with PROSPERO, number CRD42019132243.ResultsWe obtained 6467 citations and identified 29 RCTs including 13,596 participants; 86% of these trials were low risk or of uncertain risk bias. In NMA, ORs compared with sham injection for the proportion of patients gaining 15 or more letters (12,699 participants from 23 trials) ranged from 4.05 [95% Bayesian credible interval (CrI) 1.62-10.11] for ranibizumab quarterly regimen to 8.57 (95% CrI 4.66-15.73) for a ranibizumab treat-and-extend regimen. No difference was found between sham injection and anti-VEGF regimens for ATC events (11,500 participants from 18 trials). Results for the primary outcome did not substantially change in sensitivity analyses after removing studies at high risk of bias and small sample size (n < 100), respectively.ConclusionThe treat-and-extend regimen of ranibizumab and aflibercept are the preferred anti-VEGF regimens for nAMD. Bevacizumab treat-and-extend regimens need more head-to-head comparisons with other regimens or sham injection for advanced application. The treat-and-extend regimen proved to be the most effective regimen for each anti-VEGF drug in the NMA. Pegaptanib every 6 weeks and Conbercept quarterly are unable to satisfy the best corrected visual acuity (BCVA) improvement requirement of nAMD patients.

Project description:ImportanceLimited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu).ObjectiveTo determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated.Design, setting, and participantsThis cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included.InterventionBrolucizumab injections.Main outcome and measuresIncidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors.ResultsOf 10 654 and 11 161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10 654 [90.9%] and 10 487 of 11 161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10 487 [68.2%]), and most were from women (6105 of 10 654 [57.3%] and 6452 of 11 161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events.Conclusions and relevanceThe incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.

Dataset Information

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

Introduction

Methods

Results

Conclusion

Publications

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

Similar Datasets

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