• Written By: Chirag P. Shah, MD, MPH

    This study reports that ranibizumab and bevacizumab had similar effects on visual acuity when patients followed the same dosing regimen for two years. As-needed treatment yielded less improvement in visual acuity, whether instituted at enrollment or after one year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events but there was a higher rate of serious adverse events with bevacizumab, the significance of which the authors say is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

    This study, which was part of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) and reported in the July issue of Ophthalmology, included 1,107 wet AMD patients initially assigned to treatment with ranibizumab or bevacizumab with either monthly or as-needed dosing. At one year, patients in the monthly groups were reassigned randomly to monthly or as-needed treatment without changing drug assignment.

    Among those treated with monthly ranibizumab for two years, mean increase in visual acuity from baseline was 8.8 letters, compared with 7.8 in the bevacizumab monthly group (P = 0.21). Ranibizumab had a slight edge in the as-needed arm at two years compared with bevacizumab (mean letter gain of 6.7 vs. 5.0). Mean gain was greater for monthly than as-needed treatment (difference, 2.4 letters; P = 0.046), with the greatest difference (3.8 letters) between ranibizumab monthly and bevacizumab as-needed. The authors say this may be the result of more lesion growth, fluorescein leakage and residual fluid on OCT in eyes treated as-needed.

    Groups switched from monthly treatment during the first year to as-needed in the second year lost vision (1.8 for ranibizumab and 3.6 for bevacizumab). For both drugs, the average number of letters gained was similar between those treated as-needed for two years and those switched to as-needed after a year of monthly treatment.

    The authors note that the magnitude and durability of the therapeutic effect in all treatment groups is remarkable when considering the natural history of wet AMD and the modest efficacy of treatments before bevacizumab and ranibizumab. At two years, 60 percent or more of patients in all groups had 20/40 vision or better, which was dramatically better than among patients who were untreated (< 10 percent) or treated (< 15 percent) with methods available before 2005.

    Anatomically, mean retinal thickness was 29 µm less in patients treated monthly compared to as-needed (P = 0.005). The proportion without fluid on OCT ranged from 13.9 percent in the bevacizumab as-needed group to 45.5 percent in the ranibizumab monthly group. However, both drugs substantially and immediately reduced fluid in or under the retina.

    Eyes treated monthly vs. as-needed developed more geographic atrophy. The highest proportion of eyes developing atrophy occurred in the ranibizumab monthly group, with 21 percent developing nonfoveal atrophy and 4.7 percent developing foveal atrophy.

    Major adverse effects were similar between ranibizumab and bevacizumab groups, including death (5.3 vs. 6.1 percent), arteriothrombotic events (4.7 vs. 5.0 percent) and venous thrombotic events (0.5 vs. 1.7 percent). However, serious systemic adverse events were less likely in those treated with ranibizumab compared to bevacizumab (32 vs. 40 percent, P = 0.004).