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After 2 years of treatment, the vascular endothelial growth factor (VEGF) inhibitors ranibizumab (Lucentis) and bevacizumab (Avastin) are proving similar in ability to improve vision in patients with wet age-related macular degeneration (AMD), researchers found.

Mean gains in visual acuity were similar for both ranibizumab (Lucentis) and bevacizumab (Avastin) (P=0.21), although patients who had monthly injections did better than those who took them on an as-needed basis (P=0.046), Frederick Ferris, MD, of the National Eye Institute, and colleagues reported in the Journal of Ophthalmology.

"At the end of the day, we can be confident in saying that as far as visual acuity, there's little difference between the two drugs," Ferris told MedPage Today.

The 2-year results of the Comparison of AMD Treatment Trials (CATT) study are also similar to the one-year results in that they found a persistent higher risk of serious systemic adverse events for bevacizumab patients (HR 1.30, 95% CI 1.07 to 1.57, P=0.009).

Ferris noted that these aren't the typical side effects one would expect with VEGF inhibitors, such as cardiovascular events. Rather, it's a "mishmash" of events including gastrointestinal side effects that seems to be worse with bevacizumab.

He said there doesn't appear to be a clear explanation for the finding: "That's something that we are going to have to pay attention to. There are some curious things about it. For example, people getting less Avastin had more serious adverse events -- and that seems 'odd' at best."

A total of 1,107 patients with wet AMD were followed for 2 years after having been assigned to ranibizumab or bevacizumab either once-monthly or on an as-needed basis.

After a year, those on the monthly dosing schedule were randomly re-assigned to stay on their current dosing regimen or move to the as-needed group.

Ferris and colleagues found that overall, among patients who were on the same dosing regimen for 2 years, the mean gain in visual acuity in terms of mean letters gained from baseline was similar for both drugs:

• Monthly: ranibizumab 8.8, bevacizumab 7.8
• As-needed: ranibizumab 6.7, bevacizumab 5.0

The mean gain in letters was significantly greater (a difference of 2.4) for those who had monthly shots than for those who took them as-needed, although monthly eye injections may not be so appealing to patients, the researchers cautioned.

Other secondary parameters offered similar insights. For instance, the proportion of patients who didn't suffer a decrease in vision of 15 letters or more ranged from 88.4% on as-needed bevacizumab to 93.3% for monthly ranibizumab.

And the proportion of patients without fluid on optical coherence tomography (OCT) ranged from 13.9% in the bevacizumab as-needed group to 45.5% for those on monthly ranibizumab.

However, rates of geographic atrophy trended significantly in the other direction, ranging from 25.8% in the monthly ranibizumab group to 12.9% in the bevacizumab as-needed group, and was greater overall in patients who had monthly shots (P=0.007).

Ferris said patients who were switched from the monthly group to an as-needed regimen "wound up with the same change in visual acuity as if they'd been on the as-needed treatment throughout the trial."

Switching to the less regimented group indeed led to a greater mean decrease in vision during year two (-2.2 letters, P=0.03) and fewer patients were fluid-free on OCT if they had been switched to getting the shots as-needed (P<0.0001).

Rates of death, MI, and stroke didn't differ between drugs, but other systemic serious adverse events were greater with bevacizumab (39.9% versus 31.7%).

After adjustment, the higher risk with bevacizumab was still significant (RR 1.30, 95% CI 1.07 to 1.57, P=0.009) and appeared to be higher with patients who were treated on an as-needed basis, though that finding wasn't significant.

Costs were also far higher for ranibizumab, which is specifically indicated for wet AMD (bevacizumab is used off-label in the condition). The estimated 2-year drug cost per patient varied from $705 in the bevacizumab as-needed group to $44,800 in the monthly ranibizumab group, the researchers reported.

"Patients and doctors are going to have to discuss the risks and benefits, including cost, and decide what's best for them," Ferris said. In the paper, he and colleagues wrote that the "choice of drug and dosing regimen for patients must balance the comparable effects on vision, the possibility of true differences in adverse events, and the 40-fold difference in cost per dose between ranibizumab and bevacizumab."

He added that ophthalmologists are looking to results of the IVAN study, which is being presented along with the 2-year CATT results at the Association for Research in Vision and Ophthalmology (ARVO) meeting later this week in Fort Lauderdale, Fla., for further assessment of the comparative effectiveness of the drugs, as well as the risk of serious adverse events.

Ferris also noted that overall, VEGF inhibitors have vastly improved the treatment of AMD, which has been shown to have benefits over the current standard of care, laser photocoagulation.

"The key fact is that these drugs, whether it's Avastin or Lucentis, ... have saved hundreds of thousands of people from losing vision," he said.

Last week, the Office of the Inspector General recommended that the Centers for Medicare and Medicaid Services establish a national payment policy for bevacizumab in wet AMD, given its cost savings and comparative efficacy.

CMS also has been debating whether to open a national coverage decision for the anti-VEGF class in diabetic macular edema.

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