The results of a two-year trial led by Queen’s scientist, Professor Usha Chakravarthy and published in The Lancet today (Friday 19 July), show that two drug treatments Lucentis and Avastin are equally effective in treating neovascular or wet age-related macular degeneration (wet AMD).
Wet AMD is a common cause of sight loss in older people with at least 23,000 older people diagnosed with the condition in the UK each year. Without treatment two thirds of people with this condition will experience severe loss of sight within two years of being diagnosed.
Lucentis, the drug most commonly used in the UK at present to treat wet AMD, costs about £700 per injection and Avastin costs about £60 per injection. The NHS could save £84.5 million annually based on injecting 17,295 eyes each year by switching from Lucentis to Avastin. Avastin is already used to treat wet AMD in some parts of the UK and extensively elsewhere in the world and also for other eye conditions.
Over the past five years, a team of scientists and eye specialists from 23 hospitals and UK universities, including Queen’s University Belfast, University of Bristol, University of Liverpool, University of Oxford and University of Southampton, have investigated whether Lucentis and Avastin and the way they are given are equally effective and safe.
610 people with wet AMD entered a two-year trial known as IVAN which is one of the largest ever carried out in the field of eye disease in the UK. Patients received injections of the drug into the affected eye every month for the first three months. Patients were then subdivided to receive the injections at every visit (monthly group) or only if the specialist decided there was persistent disease activity (as needed group).
The IVAN study’s two year results show that sight was equally well preserved with either of the two drugs. Giving the treatment regularly every month, resulted in slightly better levels of sight which was detected through testing of near visual acuity and contrast sensitivity. The ‘as needed’ group received on average 13 injections over the two year period compared to 23 for the monthly treatment group. However, continuous treatment caused a higher proportion of eyes to develop a condition known as geographic atrophy which is a thinning of the retina and its blood supply.
Professor Usha Chakravarthy of Queen’s University Belfast’s Centre for Vision and Vascular Science, who led the research study team, said: “The IVAN results at the end of year two show that Lucentis and Avastin have similar functional effectiveness regardless of the drug received. With respect to monthly versus as needed treatment, while there was marginally better eyesight in the former, the development of atrophy is a matter of concern in the longer term.”
Professor Barnaby Reeves and Dr Chris Rogers, Co-Directors of the Bristol Clinical Trials Evaluation Unit based at the University of Bristol, added: “The Bristol Clinical Trials Evaluation Unit (CTEU) is proud to have collaborated on this ground-breaking study. The 610 patients on the trial made over 12,000 visits during the two-year study.
“About half of the sites had not previously taken part in such a trial and the high quality of the data is a credit both to them and to the CTEU staff, who provided the robust comprehensive clinical trial infrastructure required to deliver the trial successfully.”
The IVAN study was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme. The Belfast Health and Social Care Trust sponsored the clinical trial. Professor Ian Young, Director of Research and Development at the Trust, said: “The findings of the IVAN study will be of great importance for the management of patients with AMD throughout the world. Research to improve patient care is a key aspect of the work of Belfast Trust, and we are committed to sponsoring and leading important clinical trials of this kind which allow our patients early access to new treatments.”
Bernadette Hannigan, Director of Research & Development at the Department of Health, Social Services and Public Safety, who supported the trial, said: “With increasing life expectancy and a growing proportion of older people in the population, slowing the progress of conditions like AMD is key to maintaining their independence. The IVAN trial is an example of research led from Northern Ireland with international significance – the findings have the potential to influence how AMD is managed in the future.”
The IVAN study also monitored the drugs for serious adverse events which included death, heart attacks, strokes, and any other event that was life threatening, disabling or resulted in hospitalisation. These were similar for the two drugs. However, deaths occurred less frequently in the group that received monthly treatment, although there were fewer deaths overall among people taking part in the trial than were expected based on their age and gender and national death rates. When these safety results were combined with those of a similar study called the CATT trial which was performed in the USA, the resultant findings continued to indicate fewer deaths when treatment was given monthly.
The researchers state that their findings will be of relevance to the next round of technology appraisals by the National Institute for Health and Care Excellence and could lead to important changes to the way wet AMD is treated. In the meantime, for an older person starting a course of Lucentis or Avastin, it will be important to explain the trade-off between the number of injections, and the chances of developing geographic atrophy and dying in two years.
Paper: Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: two year findings of the IVAN randomised controlled trial l by Usha Chakravarthy, PhD, FRCS (Queen’s University Belfast); Chris A Rogers, PhD & Barnaby C Reeves, DPhil, Lucy Culliford (University of Bristol); Simon P Harding, MD (University of Liverpool); Susan M Downes, MD (Oxford Radcliffe Hospitals); Andrew J Lotery, MD, PhD (University of Southampton), The Lancet, 19 July 2013
The hospitals and universities involved in the trial include: Addenbrooke’s Hospital, Cambridge; Aintree University Hospitals NHS Foundation Trust; Aston University Day Hospital, Birmingham; Blackburn Royal Infirmary; Blackpool Victoria Hospital; Bradford Royal Infirmary; Brighton and Sussex University Hospital; Bristol Eye Hospital; Frimley Park Hospital, Surrey; Maidstone Hospital; Manchester Royal Eye Hospital; New Cross Hospital, Wolverhampton; Oxford Eye Hospital, Oxford; Queen Elisabeth Hospital, King’s Lynn; Queen’s Medical Centre, Nottingham; Royal Victoria Hospital, Belfast; Royal Victoria Infirmary, Newcastle; Southampton University Hospitals Trust; Southend Hospital; St Paul’s Eye Unit, Liverpool; Sunderland Eye Hospital; The Birmingham and Midland Eye Centre; The Royal Hallamshire Hospital, Sheffield and Torbay Hospital.
The results of the trial were first revealed at the 2013 Association for Research and Ophthalmology Annual Meeting on May 6 – 10 in Seattle, USA which is the world’s largest gathering of international eye and vision researchers.
Wet AMD is a condition in which abnormal blood vessels develop in the macula of the eye . The macula is the central part of the retina which is responsible for detailed vision. The new blood vessels can be fragile and leak blood and fluid which cause the macula to swell and damage occurs rapidly. The damage may also cause scarring of the retina. Although loss of central vision can happen quickly, eye care professionals can slow down or stop the progression of wet AMD if it is detected before severe vision loss occurs. With wet AMD, abnormally high levels of vascular endothelial growth factor (VEGF) are secreted in the eyes. This substance promotes the growth and leakage of new abnormal blood vessels. Avastin and Lucentis are both injected in to the eye and block the effects of the VEGF.
The National Institute for Health Research Health Technology Assessment (NIHR HTA) programme funds research about the effectiveness, costs, and broader impact of health technologies for those who use, manage and provide care in the NHS. It is the largest NIHR programme and publishes the results of its research in the Health Technology Assessment journal, with over 600 issues published to date. The journal’s 2010 Impact Factor (4.197) ranked it in the top 10% of medical and health-related journals. All issues are available for download, free of charge, from the website. The HTA programme is funded by the NIHR, with contributions from the Chief Scientist Office (CSO) in Scotland and the National Institute for Social Care and Health Research (NISCHR) in Wales.
The National Institute for Health Research provides the framework through which the research staff and research infrastructure of the NHS in England is positioned, maintained and managed as a national research facility. The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world class facilities (both NHS and university), conducting leading edge research focused on the needs of patients.