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Off-Label Use of Bevacizumab for the Treatment of Age-Related Macular Degeneration

What is the Evidence?

  • Review Article
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Abstract

There is an active and controversial debate about the role of intravitreal bevacizumab versus approved drugs in the treatment of neovascular age-related macular degeneration (AMD). Because bevacizumab was available prior to the launch of ranibizumab, off-label use of the former became widespread and the cancer drug bevacizumab is the most commonly used medication in ophthalmology nowadays.

This review considers every publication identified in MEDLINE using the keywords ‘bevacizumab’ and ‘Avastin’ between 1 June 2005 and 31 July 2008. The search identified 511 papers that were evaluated. In 33 studies, there was consistent and clear evidence for the efficacy of bevacizumab in neovascular AMD. However, the highest grade studies (three prospective, randomized, controlled trials) did not attain better than grade 2b level of evidence, and objective evaluation of the benefit of bevacizumab relative to representative controls was therefore not possible. Certainly, the available evidence is inferior to that obtained from the approval studies of ranibizumab and this should influence treatment selection and guidance of patients. These considerations indicate that important quality criteria need to be included in future studies to ensure more meaningful conclusions can be drawn. These include clearly defined inclusion criteria, information about the recruitment procedure (including data on withdrawals, excluded patients, concealed treatment allocation, use of intention-to-treat analyses and blinded assessment procedures).

Although preclinical studies have almost exclusively found bevacizumab to be safe, the design utilized in clinical case series cannot rule out a possible increase in adverse events, which already show a high spontaneous incidence in elderly AMD patients. The superior evidence level for ranibizumab and the limited safety data for bevacizumab must be taken into consideration when evaluating the costs that a healthcare system is willing to spend. However, the superior grade of evidence for ranibizumab should not be confused with the (still missing) evidence for superior efficacy.

The results of ongoing randomized, controlled, comparative trials will provide further data on the efficacy and cost effectiveness of bevacizumab and ranibizumab in the treatment of AMD. In the meantime, patients should be informed about the alternatives, the price differences and the restricted liability issue when off-label use of bevacizumab is offered.

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  1. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Schleichstrasse 12-1572076, Tuebingen, Germany

    Focke Ziemssen, Karl Ulrich Bartz-Schmidt & Martin S. Spitzer

  2. Eye Hospital, Schleswig-Holstein University Campus Luebeck, Luebeck, Germany

    Salvatore Grisanti

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  1. Focke Ziemssen
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Ziemssen, F., Grisanti, S., Bartz-Schmidt, K.U. et al. Off-Label Use of Bevacizumab for the Treatment of Age-Related Macular Degeneration. Drugs Aging 26, 295–320 (2009). https://doi.org/10.2165/00002512-200926040-00002

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