Comparative effectiveness and harms of intravitreal antivascular endothelial growth factor agents for three retinal conditions: a systematic review and meta-analysis

Abstract

Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on best-corrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (≥ 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.

Changing indications for intravitreal anti-vascular endothelial growth factor injections at the university college hospital, Ibadan, Sub-Saharan Africa

“…This may have been supported by the fact that anti-VEGF therapy remains a mainstay of treatment. 3,14,15 Similarly, advances in the medical field that has led to the increased population of the elderly who may have accounted for the cases of wet ARMD. 16 On the other hand, the proportion of patients with proliferative sickle cell retinopathy (SCR) needing intravitreal anti-VEGF has significantly reduced in the centre (from 16 to 3% over 5 years).…”

Off-label use of bevacizumab for wet age-related macular degeneration in Europe

“…The nature of the determinants might be complex, and they may also interact with each other. Still, multiple studies have proven bevacizumab to have comparable efficacy and safety to the registered anti-VEGF drugs, and there is also evidence that bevacizumab is the most costeffective drug for wet AMD [49,50]. In the end, the considerable European differences in ophthalmic bevacizumab use could mainly be a matter of principle and reflect differing attitudes towards off-label treatment itself.…”

Anti-VEGF therapy: higher potency and long-lasting antagonism are not necessarily better

“…In most clinical trials using intravitreal anti-VEGF therapy, the incidence of CVA, myocardial infarction (MI), and death is not significantly elevated, but these studies are underpowered for assessing small differences in rare events (23). Similarly, the incidence of systemic AEs did not differ between various anti-VEGF drugs, although one diabetic macular edema (DME) trial reported more arterial thrombotic events with ranibizumab versus aflibercept (24). Nevertheless, for some risk populations, such as patients with diabetes or a history of recent MI or CVA, there may be an increased risk with sustained suppression of systemic VEGF levels.…”