Off-label use of Avastin for AMD: Is cheaper better?

People's faces look less clear to you, and words in a book seem blurry. Lately you need more light for reading. Straight lines appear wavy or crooked. Any of those changes in eyesight could signal an eye disease known as age-related macular degeneration (AMD), the leading cause of blindness and severe vision loss in older people. About 1.75 million Americans suffer from its advanced stage.

AMD can rob you of your central vision, the kind that's needed for reading, driving, and recognizing faces. Dry AMD, the more common and often less severe form occurs when the macula, the part of the retina that's responsible for central vision, slowly breaks down with age. More damaging still is wet AMD, which develops when abnormal blood vessels grow behind the retina and leak blood and fluid, often causing rapid and severe sight loss.

Fortunately retina specialists can combat wet AMD with a new class of drugs, known as VEGF inhibitors, that are injected directly into the eye to halt the growth of those blood vessels. Two drugs in that class are widely used. Ranibizumab (Lucentis) is approved by the Food and Drug Administration for the treatment of AMD, and well-designed clinical trials have found that it arrests the course of the disease and even improves vision. Bevacizumab (Avastin) is a similar drug that's approved to treat cancer by preventing the growth of blood vessels that nourish tumors. Some studies have found that when Avastin is used in the eye its effect is comparable to Lucentis, though evidence is limited to case studies and descriptive reports. Avastin hasn't been evaluated for AMD in randomized controlled trials and it's not approved to treat AMD. Yet many retina specialists use it "off label."

Which drug would you use? If the choice seems obvious, read on.

Lucentis is reported to stabilize vision in about 95 percent of patients and actually improve vision in up to 40 percent. But before Lucentis hit the market, retina specialists began using Avastin off-label, and it was quickly and broadly adopted as a first-line therapy for AMD. The few published studies on treatment of AMD with Avastin--trials that did not compare the drug with other AMD treatments--coupled with results in clinical practice have been so encouraging that Medicare usually covers the cost despite the lack of formal approval. And price is at the crux of this debate: Lucentis costs $2,000 per injection while Avastin is about $50. Moreover, patients must undergo a series of injections with both drugs. Although Medicare pays in either case, patients who lack insurance or have high co-payments can realize huge savings with Avastin. Not surprisingly, many physicians prefer to stock the less-expensive drug. And Genentech, which makes Avastin and Lucentis, has had little financial incentive to conduct additional clinical trials to gain FDA approval of Avastin to treat wet AMD.

"Avastin is one of the most commonly used drugs worldwide for the treatment of wet AMD," says Daniel F. Martin, M.D., chairman of the Cole Eye Institute at the Cleveland Clinic and head of a new study that will compare the two drugs directly. "We have a responsibility to understand the long-term visual and safety results associated with Avastin and to understand how these results compare to Lucentis." Funded by the National Eye Institute, a division of the National Institutes of Health, the study is currently enrolling participants at 43 centers around the country. Results are expected in 2011. (For more information, go to http://clinicaltrials.gov/show/NCT00593450.)

While they're not fully known for the treatment of AMD, the complications reported to date appear to be limited, and some—such as eye infection, retinal detachment, bleeding, and increased pressure in the eye—may stem from the injection rather than the drug. Those reactions are uncommon but can lead to severe loss of vision.

When used to treat cancer, Avastin has caused serious complications in some patients, including gastrointestinal perforations, impaired wound healing, hemorrhaging in the lungs, stroke, heart attack, hypertension, heart failure, and kidney problems. Other reported side effects include mild increases in blood pressure, dizziness, and ringing in the ears. However, those patients were given much higher doses, and the drug was administered intravenously so that it may affect other organs, not just a localized area. AMD patients receive Avastin only in the eye and in fewer doses that are 300 to 500 times lower, presumably reducing the risk of such complications. But such side effects may still be possible.

Your ophthalmologist should have extensive experience with all the treatment options for wet AMD. Ask if he or she regularly treats patients with the condition, and discuss treatments based on your diagnosis and what outcome you can expect with each. For example, laser surgery and photodynamic therapy may slow the progression of vision loss, but they have not been shown to improve vision.

If you and your doctor decide to start with Avastin, your doctor should screen you for medical conditions that could increase your risk for complications. Tell him or her if you have a recent history of heart attack or stroke, or if you're at increased risk for either.

Other safety precautions:

• If you need to have surgery for any reason, inform your surgeon and any other physicians, including dentists, that you are undergoing Avastin treatments. In some cases, your physician may want you to stop treatment for a time before and after your surgery. Also, if you're scheduling surgery, be sure to discuss it ahead of time with your ophthalmologist.
• Do not rub your eyes or swim for three days after each injection.
• Immediately contact your ophthalmologist if you develop any of the following signs of eye infection or other complications: pain, blurry or decreased vision, sensitivity to light, redness of the eye (compared with immediately after an injection), or discharge from the eye.

Obtain emergency medical care if you have symptoms that could indicate a systemic complication. Those include:

• abdominal pain with constipation and vomiting
• abnormal bleeding
• chest pain
• severe headache
• slurred speech
• weakness or numbness on one side of the body

Keep all post-injection appointments or scheduled phone calls to your doctor to check for complications.

Bottom line: Avastin is a commonly used drug to treat wet AMD, though it is not FDA-approved for this use. It is likely that a doctor will discuss using it with you if you need it. Our advice: Consider Avastin if cost is an issue and you've talked with your doctor about all available treatments.