Macular degeneration study fuels drug therapy debate

An Ontario study of two drugs — one approved to treat macular degeneration, and the other used off-label to fight the eye disease —suggests neither increases stroke or heart attack risk, adding to debate over why both Roche drugs aren't covered under provincial drug plans when used for AMD.

Ontario study finds AMD drug Lucentis, Avastin used off-label don't increase vascular risks

Testing for macular degeneration is simple, but treatment for the common eye disease that can cause blindness isn't so straightforward. A new Ontario study released Wednesday suggests two drugs, one approved for AMD and the other used off-label, don't increase the risk of stroke or heart attack. (Ontario Opticians Association/Canadian Press)

An Ontario study of two drugs — one approved to treat wet age-related macular degeneration, and the other used off-label to fight the eye disease —suggests neither increases the risk of stroke or heart attack, adding to the debate over why both treatments from the same company aren't covered under provincial drug plans when used for AMD.

AMD, which affects about one million Canadians mostly over age 65, is a progressive condition that damages the macula in the eye, and is a leading cause of blindness.

Researchers from Toronto, Hamilton and Kingston, Ont., followed 91,378 older adults with a history of retinal disease between April 1, 2006 and March 31, 2011, to determine if injections of bevacizumab (trade name Avastin) or ranibizumab (Lucentis) could be linked to increased vascular risks including stroke, heart attack or congestive heart failure.

Avastin and Lucentis, both manufactured by Roche, are vascular endothelial growth factor (VEGF) inhibiting drugs, and both have the potential to cause vascular side-effects.

What is macular degeneration?

Age-related macular degeneration (AMD) affects the macula, the part of the retina responsible for the sharp, central vision needed to read or drive, for instance. AMD is classified into two types: dry (also known as non-exudative or non-neovascular) and wet. Dry AMD is more common, accounting for about 90 per cent of AMD cases. It may cause little or no visual symptoms until it is more advanced, and can lead to wet AMD, a common cause of blindness

Source: CNIB

However, the research done at Ontario's Institute for Clinical Evaluative Sciences (ICES), and published in Wednesday's edition of BMJ (British Medical Joural) concludes injections of these drugs into the eyes of patients with retinal disease did not increase such risks.

"The take-home message from our study is we weren’t able to find increased risks of these adverse vascular events with either drug," Dr. Robert Campbell, who's with the departments of ophthalmology at Queen's University and Hotel Dieu and Kingston General Hospitals, said in an interview with CBC News on Wednesday morning. 

Campbell said the two drugs were studied, with funding from the Ontario government and the Canadian Institutes of Health Research and no pharmaceutical company backing,  because they are commonly used to treat the eye disease. However, he added, while Lucentis is approved specifically for AMD, Avastin is approved only to treat certain cancers but is used off-label to treat the eye disease.

Cost a factor in use of both drugs

Campbell stressed that while the study he was involved in complements and adds to results of other studies that "didn't detect differences in vascular events, the risk of vascular events isn’t likely going to drive the decision of which drug is best – it would be based on other things like cost and any other side-effects."

Both cost and safety have been factors — and at the centre of controversy in Canada and other parts of the world — when deciding which drug should be used to treat AMD.
Roche, based in Switzerland, is the maker of both Lucentis, approved for the treatment of wet age-related macular degeneration (AMD), and Avastin, which isn't approved for AMD but is commonly used to treat the eye disease. (Associated Press)

Previous reports have pegged the cost of using Lucentis at anywhere from $1,100 to $2,000 a month, while Avastin's cost has been variously reported in the media as costing anywhere from $7 to about $100 a shot. A call to Roche's Canadian office was returned Wednesday afternoon, but the spokeswoman referred CBC News's request for an interview to the company's Swiss office, although that call wasn't immediately returned.

While Lucentis is included in most Canadian provincial drug formularies to pay the cost to patients with AMD, Avastin isn't covered under provincial plans if used for AMD.

In fact, in a public advisory issued in December, Health Canada stressed Avastin is only authorized, in combination with chemotherapy, for the treatment of people diagnosed with colon and rectal cancer as well as lung cancer, and not for treatment of eye disease.

Warnings about possible contamination

Health Canada also warned about reports of severe eye inflammation leading to blindness in patients in the U.S., saying, "The cases appear to be due to contamination after repackaging single-use Avastin vials into several syringes."

Lawsuits have been launched in the U.S. by several patients alleging Avastin injections caused their blindness. The Food and Drug Administration (FDA) reported that about a dozen infections in Miami were traced back to a single lot of Avastin and a pharmacy that had repackaged the drug for use in the eye.

Campbell stressed in the interview with CBC that repackaging of Avastin for eye treatment use is just one of the areas that need to be looked at carefully, because of the potential for eye infection and inflammation.

When asked if he thought his study might prompt Roche to seek approval for the use of Avastin for AMD, Campbell said, "I don’t think our study is likely to have that effect – it’s one piece of the puzzle. There are lots of other studies as well. People are likely to use our study in conjunction with other studies and with policymakers to decide what drugs to use and fund."