Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration

Abstract

Objective To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for two years and to describe the impact of switching to as-needed treatment after a year of monthly treatment. Design Multicenter, randomized clinical trial. Participants Patients (N=1107) who were followed during Year 2 among 1185 patients with neovascular age-related macular degeneration (AMD) who were enrolled in the clinical trial. Interventions At enrollment, patients were assigned to four treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At one year, patients initially assigned to monthly treatment were randomly reassigned to monthly or as needed treatment, without changing the drug assignment. Main Outcome Measure Mean change in visual acuity. Results Among patients following the same regimen for two years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference: −1.4 letters; 95% confidence interval (CI): [−3.7, 0.8]; p=0.21). Mean gain was greater for monthly than for as-needed treatment (difference: −2.4 letters; CI: [−4.8, −0.1]; p=0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug p=0.0003; regimen p<0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (−2.2 letters, p=0.03) and a lower proportion without fluid (−19%, p<0.0001). Rates of death and arteriothrombotic events were similar for both drugs (p>0.60). The proportion of patients with ≥1 systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio 1.30; CI [1.07, 1.57]; p=0.009). The majority of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF). Conclusions Ranibizumab and bevacizumab had similar effects on visual acuity over a two-year period. Treatment as needed resulted in less gain 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. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration: how to alleviate the clinical burden with maintained functional results

“…The 'observe-and-plan' regimen allows for elimination of monthly repeated evaluation visits during the treatment plans, thereby reducing the number of ophthalmic assessments to one-third (33%) and one-fourth (24%) during the first and second year, respectively, as compared with the monthly visits required in PRN regimens. 11,12,16 Thus far, various Figure 3 Distribution of the first measured interval after loading doses (horizontal axis), plotted against the last applied interval at month 24 (vertical axis), for all eyes that underwent treatment with ranibizumab for neovascular age-related macular degeneration according to the studied regimen 'observe and plan'. The term 'observation' is equivalent to any interval longer than 3 months.…”

“…Simply reducing the intravitreal injections to a fixed retreatment every 3 months was significantly inferior to monthly injections and resulted in the loss of initial visual acuity (VA) improvement. [8][9][10] Although the individually adjusted pro re nata (PRN) retreatment regimen was able to reduce the number of retreatments with (near) noninferiority of visual results as compared with monthly retreatment, 11,12 this regimen still requires monthly monitoring visits to detect disease recurrence and determine the need for retreatment. In a context of chronic care management and indefinite treatment duration, monthly monitoring visits place a heavy burden on ophthalmic institutions, with new patients being regularly added because of the high incidence of nAMD.…”

Optical Coherence Tomography–based Correlation Between Choroidal Thickness and Drusen Load in Dry Age-Related Macular Degeneration

“…31,32 Not only were OCT criteria an outcome measure in these trials but they were also used as part of treatment criteria. However, to date, there has been a paucity of clinical trials for dry AMD.…”

The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity

“…12 Currently, the only effective therapy is for NVAMD and although this affects modest numbers (10-15% of advanced forms of AMD [9][10][11][13][14][15] ) compared with non-NVAMD (NNVAMD), it carries a disproportionate risk for patients in terms of severity of vision loss. [16][17][18][19][20] Anti-angiogenic therapy (also called antivascular endothelial growth factor (VEGF) therapy) is now the gold standard for the treatment of NVAMD. [16][17][18][19] Over the past number of years, it has revolutionized our ability to not only preserve but also improve vision in many sufferers.…”

“…[16][17][18][19][20] Anti-angiogenic therapy (also called antivascular endothelial growth factor (VEGF) therapy) is now the gold standard for the treatment of NVAMD. [16][17][18][19] Over the past number of years, it has revolutionized our ability to not only preserve but also improve vision in many sufferers. Meanwhile, several clinical trials are evaluating newer agents as treatments for NNVAMD but for this larger group of patients, dietary supplements as per the Age-Related Eye Disease Study data remain their only recourse to what is essentially a low-efficacy intervention.…”