Weighing the risks and benefits of combination therapy in AMD

April 1, 2006

We need stronger evidence to support the combination of PDT with anti-VEGF therapy or corticosteroids before combination therapy becomes standard care for many of these lesions.

Bressler provides an update on the off-label use of PDT for occult with no classic lesions with presumed recent disease progression and PDT in combination therapy with steroids and anti-VEGF agents, such as pegaptanib sodium (Macugen, Pfizer/OSI), ranibizumab (Lucentis, Novartis Ophthalmics/Genentech) and bevacizumab (Avastin, Genentech).

PDT with verteporfin: what do we know so far?

"While the totality of other vision outcome data from the VIP trial warranted consideration of this treatment, especially with smaller lesions or lower (worse) levels of visual acuity, based on this, the evidence was probably not strong enough to label the therapy adequate for treatment of similar occult with no classic lesions by the FDA," Bressler said.

"Similar outcomes were seen at the 24-month intent-to-treat analysis. There was only a small difference in favour of verteporfin at the 12- and 24-month examinations and for both three-line and six-line vision loss," Bressler recounted. No additional adverse events occurred in the VIO trial compared with previous trials of verteporfin.

For the patients with vision that was less than 20/200 at the 24-month examination, he added, the results appeared to slightly favour the patients who received verteporfin. There were fewer eyes in the verteporfin group with decreases in vision and more eyes with a greater increase in the number of letters.

"Looking at the evidence, in its entirety, on all occult and no classic lesions in the verteporfin trials, a moderate difference in outcomes was noted in the VIP trial while a smaller difference was reported in the VIO trial. Overall, there was a slight balance in favour of verteporfin therapy for reducing the risk of at least a three-line loss of vision. The 12- and 24-month data do show better visual outcomes for the verteporfin group and the safety results are consistent with what was known previously. However, the results for the primary outcome, i.e., less than a three-line loss of vision, were not significant and probably do not warrant an FDA change in the labelling of the drug. The outcomes from all trials do indicate a role for PDT with verteporfin, pegaptanib sodium or bevacizumab for these lesions until ranibizumab becomes available, when, it is predicted, this agent will become the treatment of choice for such cases," he said.