Article Text
Abstract
Objectives To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV).
Design Systematic review and random-effects meta-analysis.
Methods Multiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias.
Results 19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6–9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients.
Conclusions Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen.
PROSPERO registration number CRD42015022041.
- ranibizumab
- bevacizumab
- aflibercept
- anti-vascular endothelial growth factor
- age-related macular degeneration
- diabetic macular edema
- retinal vein occlusion
- myopic choroidal neovascularization
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Footnotes
Contributors BP screened titles, abstracts and full-text articles; abstracted and cleaned data, conducted quality assessment and drafted the manuscript. SMT led the coordination of the systematic review; drafted the protocol; screened titles, abstracts and full-text articles; abstracted and cleaned data; conducted quality assessment; and helped draft and revise the manuscript. TL screened titles, abstracts and full-text articles; abstracted and cleaned data; conducted quality assessment; helped conduct meta-analysis and reviewed the manuscript. EL screened titles, abstracts and full-text articles; abstracted and cleaned data; conducted quality assessment and reviewed the manuscript. JH conducted the analysis and interpretation of data; and reviewed the manuscript. TR helped with conceptualising the research design, drafting and revising the protocol, interpretation of data and reviewed the manuscript. GJ helped draft and revise the protocol; screened titles, abstracts and full-text articles; abstracted data; conducted quality assessment; helped interpret the data and reviewed the manuscript. AA screened titles, abstracts and full-text articles; abstracted and cleaned data; conducted quality assessment and reviewed the manuscript. JPS screened titles, abstracts and full-text articles; abstracted and cleaned data; conducted quality assessment and reviewed the manuscript. AS screened titles, abstracts and full-text articles; abstracted and cleaned data, conducted quality assessment and reviewed the manuscript. RW screened titles, abstracts and full-text articles; abstracted and cleaned data, conducted quality assessment and reviewed the manuscript. RB abstracted and cleaned data, conducted quality assessment and reviewed the manuscript. EM screened titles, abstracts and full-text articles; abstracted and cleaned data; and reviewed the manuscript. SES helped with conceptualising the research and design; interpretation of data and reviewed the manuscript. ACT conceptualised the research and design; drafted the protocol; obtained funding; assisted with data acquisition and interpretation; and drafted and revised the manuscript. ACT and BP had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.
Funding This work was supported by the Canadian Institutes of Health Research/Drug Safety and Effectiveness Network (CIHR/DSEN). SES is funded by a Tier 1 Canada Research Chair in Knowledge Translation. ACT is funded by a Tier 2 Canada Research Chair in Knowledge Synthesis. The therapeutic review was commissioned by the Canadian Agency for Drugs and Technology in Health (CADTH) and funded by a grant from the Canadian Institutes of Health Research Drug Safety and Effectiveness Network. The funders had no role in design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data sets generated and/or analysed during the current study are available from the corresponding author on reasonable request.
Presented at The data from the original therapeutic review were presented by ACT and SMT to the Canadian Drug Expert Committee in Ottawa, Ontario, on 17 November 2015.
Patient consent for publication Not required.