Anti-VEGF agent reimbursable for AMD in France

Regular monitoring of ranibizumab therapy should determine when and if to re-treat each patient.

Gabriel Coscas

PARIS – French health authorities have acknowledged that anti-VEGF therapy has been a breakthrough in the treatment of age-related macular degeneration and are providing full reimbursement for what international multicenter trials and evidence-based medicine have shown to be the new standard of care.

A large investment has been made by the French government to offer AMD patients the best medication currently available, namely Lucentis (ranibizumab, Genentech), as well as the most updated technology for diagnosis and follow-up, in spite of the high costs involved, Gabriel Coscas, MD, told Ocular Surgery News.

“Any potentially blinding disease needs to become a priority, and no sparing of time and money should ever be made,” he said.

He said he is surprised at the delay of some countries in taking provisions for reimbursement of ranibizumab treatment and at the numerous discussions on the economical burden and cost-effectiveness.

“Nobody would discuss the high costs of treating a patient for cancer. So I don’t see why anyone should oppose to investing money on a drug that can help in facing a severe and, unfortunately, increasing emergency like AMD,” Prof. Coscas said.

Monitoring with best technology

Prof. Coscas said that regular monitoring of the effects of the treatment, not predetermined limits, should decide the number and frequency of injections.

“We need close monitoring of each individual case with the use of the best available technology to evaluate the individual response to the treatment before we decide on whether and when to perform another injection,” he said.

Visual testing, fundus examination with contact lens biomicroscopy and optical coherence tomography should be mandatory between injections. If the patient shows a definite improvement and this is confirmed by fluorescein angiography, a second injection may not be needed at that moment. However, monthly visual tests, fundus examination with contact lens biomicroscopy and OCT, plus an angiographic control every 3 months for at least the first year must be performed.

AMD follow-up must be long, accurate and regular, and no scheme has been designed works for every patient, he said.

“Most specialists now use the results of the PrONTO study (Prospective optical coherence tomography imaging of patients with neovascular age-related macular degeneration treated with intraocular Lucentis) as guidance. It is a remarkable study. It is prospective, but it is not controlled, and it is based on a non-homogeneous series of only 41 patients. It is interesting. It is useful to our knowledge, but it is not evidence-based medicine,” Prof. Coscas said.

The positive aspect of the study is that it suggests a flexible, customized treatment based on regular OCT control to decide when it is time to re-treat the patient. This non-schematic schedule may, however, imply a higher risk of unforeseen recurrence and of intervening too late when the situation is severe and irreversible, he said.

OCT alone is not sufficient

“To make a good diagnosis and prognosis and to be sure of stabilization after each treatment, we need a better and more complex imaging analysis that cannot be provided by OCT alone,” Prof. Coscas said.

“When we have a patient who is 75 years old, has a drusen, has a hemorrhage, we know what is happening, but we need a confirmation with contact lens biomicroscopy. We need OCT, possibly the spectral domain OCT, to detect all the subtle changes in the different layers of the retina and to see if there is any photoreceptor damage. We also need the angiogram for confirmation that there is choroidal neovascularization, and we need the ICG angiogram to see the occult CNV,” he said.

With complete analysis, specialists will be able to make the best decision for each patient. In some cases, they will determine if the lesions are too advanced to make an improvement and avoid useless treatment. In some other cases, they will see that the treatment has been effective, that there is no more vessel perfusion and, therefore, perform no further injection. Specialists will also be able to detect the patients who are non-responders and suggest a combined treatment with PDT.

“Remember that in the management of our patients, the first eye is important, but any risk for the second eye is even more critical. A visual loss at the first eye is a disease. At the second eye, [it] is a disaster,” Prof. Coscas said.

Therefore, the limited data provided by OCT only are not sufficient.

“The second eye is more precious than gold. If we re-treat our patients when it is too late, then we lose all the benefits we had initially, and we will be responsible for something that, with the currently available treatments, could probably be avoided,” he said.

No need for off-label use of drugs in AMD

There have been positive results in the many clinical studies carried out on the use of off-label drugs, namely Avastin (bevacizumab, Genentech), Prof. Coscas said.

The suggestions about the systemic cardiovascular or pulmonary risks of this drug have had no evidence-based confirmation. Therefore, its off-label use was probably justified when ranibizumab was not available, he said.

Formal, compassionate use of bevacizumab can still be obtained in some cases when following the appropriate procedure for non-AMD neovascularization, macular edema and retinal vein occlusion, neovascular glaucoma and rubeosis iridis. Currently, there is no formally approved anti-VEGF agent available for these conditions and, therefore, doctors can still legally prescribe these drugs for off-label use.

“However, now that we have no problems of availability and reimbursement of Lucentis for AMD, there is no reason why we should use a drug that has not been officially and scientifically tested for ocular use, that is not available in the proper dosage and that we would have to prescribe illegally,” Prof. Coscas said.

High standards of care

Intravitreal injections can be performed in public hospitals or private practices that fulfill the government quality and safety standards.

“In both settings, we need to implement a strict sterile operating room protocol, defined in all details by our health authorities. We must prove that the procedure is performed in a separate, dedicated room, that asepsis is maximized and maintained in the operating field, in the preparation of the patient and during all stages of surgery,” Prof. Coscas said.

If private practices are not equipped with all of the imaging systems that are required for the diagnosis and follow-up, the patient can be referred to outside specialized centers.

“In France, there are more than 1,000 angiography machines in private practices, which means one [in] every four offices. OCT [is] also increasingly a part of the office equipment of private retinal practices. In addition, we have hospitals in every city, even in fairly small towns, and they all have complete angiography and OCT facilities,” he said.

The challenge now is achieving a more efficient organization for best patient satisfaction, which means shorter waiting times and increased time spent with the physician.

“I think that both the authorities and us, as doctors, must see this as a priority. There is no question of sparing time for treating patients, and we must fully devote our time and knowledge for each individual case,” Prof. Coscas said. – by Michela Cimberle