Macular oedema

Background

Bevacizumab (Avastin, Roche Products Ltd) is licensed as a treatment for cancer. It is a monoclonal antibody which works by inhibiting vascular endothelial growth factor A (VEGF).

VEGF is a mediator in the pathogenesis of certain eye conditions, including wet age-related macular degeneration (AMD), diabetic retinopathy and macular oedema secondary to retinal vein occlusions.

There is evidence that VEGF inhibitors can improve vision, whereas the main outcome of traditional treatments such as photodynamic therapy for AMD or laser photocoagulation for macular oedema, is to delay deterioration in vision.

There are licensed VEGF inhibitors available in the UK. Ranibizumab (Lucentis, Novartis) is licensed for the treatment of wet AMD, diabetic macular oedema (DMO) and retinal vein occlusion (RVO). Pegaptanib (Macugen) is licensed for the treatment of wet AMD.

However, these therapies are much more costly than bevacizumab for use in the eye. Ranibizumab costs £742.17 per injection according to the latest edition of the British National Formulary (ref BNF no 63). Pegaptanib costs £514 per injection.

Whilst bevacizumab does not have a license for ocular use, it is a much less costly alternative. A 4ml vial for its licensed intravenous use costs £242.66. Intravitreal use requires much smaller doses which are produced by breaking open a vial and drawing them up into a fine syringe to deliver small volumes.

Many doses for the eye can be produced from a single bevacizumab vial and therefore can be supplied for a much lower cost of approximately £50 to £100. This is one of the reasons that bevacizumab has been used in this manner since 2005.

The process of manipulating bevacizumab supplied for use in oncology is not undertaken by the sponsor (Roche) and there have been concerns raised about the risks to patients introduced via this process. The Medicines and Healthcare products Regulatory Agency (MHRA) considers that this manipulation creates an unlicensed medicine.

In this report, we provide evidence on four issues relating to the use of bevacizumab in eye conditions. These issues are those considered by NICE to be of value in helping to inform committee considerations relating to the considerations of bevacizumab as a comparator in Technology Appraisals for RVO.

The DSU will answer four questions:

1. What evidence is there relating to the pharmaceutical quality of reformulated bevacizumab as used in eye conditions in general? (section 2)

2. How widespread is Intravitreal Bevacizumab (IVB) used in the UK? (section 3)

3. What is the evidence for efficacy of IVB in adults with RVO and DMO specifically? (section 4). The evidence base around AMD is not included in this review.

4. What evidence is there regarding adverse events for IVB in eye conditions in general? (section 5). Here the evidence from ALL eye conditions is drawn upon.

DSU report

Intravitreal bevacizumab – quality, use, efficacy and safety (PDF, 1.4MB) (August 2012)

Related publication

E Poku, J Rathbone, R Wong, E Everson-Hock, M Essat, A Pandor, A Wailoo. The safety of intravitreal bevacizumab monotherpay in adult ophthalmic conditions: Systematic review. 2014 BMJ Open 4:e005244 doi:10.1136/bmjopen-2014-005244

NICE appraisals

Macular oedema (retinal vein occlusion) – ranibizumab [ID328] (February 2013)

TA274 Ranibizumab for treating diabetic macular oedema (rapid review of technology appraisal guidance 237) (February 2013)