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Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration

Overview of attention for article published in Cochrane database of systematic reviews, September 2014
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (96th percentile)

Mentioned by

news
5 news outlets
blogs
3 blogs
policy
1 policy source
twitter
39 tweeters
facebook
2 Facebook pages
wikipedia
2 Wikipedia pages
googleplus
1 Google+ user

Citations

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128 Dimensions

Readers on

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184 Mendeley
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Title
Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration
Published in
Cochrane database of systematic reviews, September 2014
DOI 10.1002/14651858.cd011230.pub2
Pubmed ID
Authors

Moja, Lorenzo, Lucenteforte, Ersilia, Kwag, Koren H, Bertele, Vittorio, Campomori, Annalisa, Chakravarthy, Usha, D'Amico, Roberto, Dickersin, Kay, Kodjikian, Laurent, Lindsley, Kristina, Loke, Yoon, Maguire, Maureen, Martin, Daniel F, Mugelli, Alessandro, Mühlbauer, Bernd, Püntmann, Isabel, Reeves, Barnaby, Rogers, Chris, Schmucker, Christine, Subramanian, Manju L, Virgili, Gianni

Abstract

Neovascular age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly populations of industrialised countries. Bevacizumab (Avastin®) and ranibizumab (Lucentis®) are targeted biological drugs (a monoclonal antibody) that inhibit vascular endothelial growth factor, an angiogenic cytokine that promotes vascular leakage and growth, thereby preventing its pathological angiogenesis. Ranibizumab is approved for intravitreal use to treat neovascular AMD, while bevacizumab is approved for intravenous use as a cancer therapy. However, due to the biological similarity of the two drugs, bevacizumab is widely used off-label to treat neovascular AMD. To assess the systemic safety of intravitreal bevacizumab (brand name Avastin®; Genentech/Roche) compared with intravitreal ranibizumab (brand name Lucentis®; Novartis/Genentech) in people with neovascular AMD. Primary outcomes were death and All serious systemic adverse events (All SSAEs), the latter as a composite outcome in accordance with the International Conference on Harmonisation Good Clinical Practice. Secondary outcomes examined specific SSAEs: fatal and non-fatal myocardial infarctions, strokes, arteriothrombotic events, serious infections, and events grouped in some Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC). We assessed the safety at the longest available follow-up to a maximum of two years. We searched CENTRAL, MEDLINE, EMBASE and other online databases up to 27 March 2014. We also searched abstracts and clinical study presentations at meetings, trial registries, and contacted authors of included studies when we had questions. Randomised controlled trials (RCTs) directly comparing intravitreal bevacizumab (1.25 mg) and ranibizumab (0.5 mg) in people with neovascular AMD, regardless of publication status, drug dose, treatment regimen, or follow-up length, and whether the SSAEs of interest were reported in the trial report. Two authors independently selected studies and assessed the risk of bias for each study. Three authors independently extracted data.We conducted random-effects meta-analyses for the primary and secondary outcomes. We planned a pre-specified analysis to explore deaths and All SSAEs at the one-year follow-up. We included data from nine studies (3665 participants), including six published (2745 participants) and three unpublished (920 participants) RCTs, none supported by industry. Three studies excluded participants at high cardiovascular risk, increasing clinical heterogeneity among studies. The studies were well designed, and we did not downgrade the quality of the evidence for any of the outcomes due to risk of bias. Although the estimated effects of bevacizumab and ranibizumab on our outcomes were similar, we downgraded the quality of the evidence due to imprecision.At the maximum follow-up (one or two years), the estimated risk ratio (RR) of death with bevacizumab compared with ranibizumab was 1.10 (95% confidence interval (CI) 0.78 to 1.57, P value = 0.59; eight studies, 3338 participants; moderate quality evidence). Based on the event rates in the studies, this gives a risk of death with ranibizumab of 3.4% and with bevacizumab of 3.7% (95% CI 2.7% to 5.3%).For All SSAEs, the estimated RR was 1.08 (95% CI 0.90 to 1.31, P value = 0.41; nine studies, 3665 participants; low quality evidence). Based on the event rates in the studies, this gives a risk of SSAEs of 22.2% with ranibizumab and with bevacizumab of 24% (95% CI 20% to 29.1%).For the secondary outcomes, we could not detect any difference between bevacizumab and ranibizumab, with the exception of gastrointestinal disorders MedDRA SOC where there was a higher risk with bevacizumab (RR 1.82; 95% CI 1.04 to 3.19, P value = 0.04; six studies, 3190 participants).Pre-specified analyses of deaths and All SSAEs at one-year follow-up did not substantially alter the findings of our review.Fixed-effect analysis for deaths did not substantially alter the findings of our review, but fixed-effect analysis of All SSAEs showed an increased risk for bevacizumab (RR 1.12; 95% CI 1.00 to 1.26, P value = 0.04; nine studies, 3665 participants): the meta-analysis was dominated by a single study (weight = 46.9%).The available evidence was sensitive to the exclusion of CATT or unpublished results. For All SSAEs, the exclusion of CATT moved the overall estimate towards no difference (RR 1.01; 95% CI 0.82 to 1.25, P value = 0.92), while the exclusion of LUCAS yielded a larger RR, with more SSAEs in the bevacizumab group, largely driven by CATT (RR 1.19; 95% CI 1.06 to 1.34, P value = 0.004). The exclusion of all unpublished studies produced a RR of 1.12 for death (95% CI 0.78 to 1.62, P value = 0.53) and a RR of 1.21 for SSAEs (95% CI 1.06 to 1.37, P value = 0.004), indicating a higher risk of SSAEs in those assigned to bevacizumab than ranibizumab. This systematic review of non-industry sponsored RCTs could not determine a difference between intravitreal bevacizumab and ranibizumab for deaths, All SSAEs, or specific subsets of SSAEs in the first two years of treatment, with the exception of gastrointestinal disorders. The current evidence is imprecise and might vary across levels of patient risks, but overall suggests that if a difference exists, it is likely to be small. Health policies for the utilisation of ranibizumab instead of bevacizumab as a routine intervention for neovascular AMD for reasons of systemic safety are not sustained by evidence. The main results and quality of evidence should be verified once all trials are fully published.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 184 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
New Zealand 1 <1%
Chile 1 <1%
Canada 1 <1%
Unknown 181 98%

Demographic breakdown

Readers by professional status Count As %
Student > Master 34 18%
Researcher 29 16%
Student > Bachelor 22 12%
Student > Ph. D. Student 21 11%
Other 12 7%
Other 40 22%
Unknown 26 14%
Readers by discipline Count As %
Medicine and Dentistry 93 51%
Nursing and Health Professions 18 10%
Agricultural and Biological Sciences 9 5%
Psychology 8 4%
Biochemistry, Genetics and Molecular Biology 7 4%
Other 19 10%
Unknown 30 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 92. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 October 2019.
All research outputs
#240,512
of 15,999,693 outputs
Outputs from Cochrane database of systematic reviews
#515
of 11,353 outputs
Outputs of similar age
#3,319
of 205,812 outputs
Outputs of similar age from Cochrane database of systematic reviews
#8
of 221 outputs
Altmetric has tracked 15,999,693 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,353 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.7. This one has done particularly well, scoring higher than 95% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 205,812 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 221 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.