Research highlights

• Research proves effectiveness of off-label drug treatment compared to licensed alternative. 
• Proof of cost-effectiveness influences changes in international clinical guidelines. 
• More people around the world can now access treatment that prevents blindness and sight loss. 

Wet age-related macular degeneration (wet AMD) is an eye condition caused by an altered production of vascular endothelial growth factor (VEGF). The disorder usually first affects people in their 50s or 60s and can lead to a rapid and severe loss of vision if not treated.

The world’s ageing population means the number of people with wet AMD could reach over 20 million by 2030 – but more people are now getting help because of research that has paved the way for more cost-effective and comfortable treatment. 

Treatment trials, breakthrough findings 

The Faculty of Health Science’s contribution to this area started when a study by Professor Barnaby Reeves and Professor Chris Rogers compared two different drugs that can treat wet AMD. 

The first licensed biological anti-VEGF, ranibizumab, entered clinical practice in 2007 and hugely improved prognosis. Challenges remained though. The high cost of the drug and the need for repeated injections into the eye put a big burden on patients and health care services.

Consequently, ophthalmologists started using an ‘off-label’ alternative, bevacizumab, and reported that it offered equivalent visual benefits at a more affordable cost.  

The IVAN trial designed by Reeves and Rogers explored the effectiveness of bevacizumab and ranibizumab in care settings in the UK NHS. The extensive study of 610 patients from 23 hospitals was the first to confirm bevacizumab was equally as successful at treating wet AMD as ranibizumab.

The research team also found that only treating active disease, which is more convenient and less stressful, delivered the same results as monthly treatment and benefitted patient well-being without detriment to eye health. 

Parallel analysis of cost-effectiveness revealed that total costs fell from £18,590 per patient for continuous treatment with ranibizumab to £3,002 per patient for discontinuous treatment with bevacizumab – potentially saving the NHS in England £102m a year with negligible differences in quality of life for patients.  

Reeves and Rogers were also co-authors of a 2014 Cochrane review that concluded that bevacizumab was as safe as ranibizumab – and that health policies recommending ranibizumab on the grounds of safety could not be sustained by evidence. 

Impact on clinical guidance and treatment practice 

The Bristol research has had a major impact on healthcare policies and guidelines in the UK.

In 2018, the National Institute for Health and Care Excellence (NICE) published clinical guidelines on the treatment of AMD that referenced findings from the IVAN trial, concluding that there are ‘no clinically significant differences in effectiveness and safety between the different anti-VEGF treatments’. 

Based on this guidance, 12 NHS Clinical Commissioning Groups (CCGs) in the North of England adopted a policy offering patients an informed choice between the two drugs. 

The impact of the research has also spread internationally. IVAN was one of only two clinical trials which directly informed the European Society of Retina Specialists’ guidance in 2014 for the management of wet AMD. By 2019, 22 of the most populous countries in the EU used bevacizumab, with five countries reporting over 70% use.  

The World Health Organisation (WHO) added bevacizumab to the Model List of Essential Medicines – a recommendation that other countries have used as evidence supporting their use of the drug.

Following a temporary ban, the Drug Controller of India re-authorised bevacizumab for use in 2016. This was a particularly significant development, because the treatment cost for wet AMD using licensed medication is unmanageable in real-life practice in most Asia-Pacific countries  

In 2015, the Brazilian Ministry of Health rejected an application for the use of ranibizumab in their publicly funded health system following an in-depth review of the evidence, including the IVAN trial.   

A new Clinical Protocol and Therapeutic Guideline for AMD followed in Brazil 2018 – providing strong evidence that cost-effectiveness has increased the availability of wet AMD treatment for disadvantaged patients, particularly in low and middle-income countries, as well hope that fewer people will suffer blindness or severe vision loss around the world in the coming years.