Clinical Studies:
CATT: Two-Year Outcomes
Citations: Martin DF, Maguire MG, Comparison of Age-related Macular Degeneration Treatments Trials Research Group, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012; 119(7): 1388-1398.
Key Points
- The CATT trial was a randomized controlled trial comparing the efficacy of bevacizumab and ranibizumab when administered on a monthly and as-needed basis.
- Patients were randomly assigned to groups defined by drug and dosing regimen. At 1 year, patients on monthly regimens were randomly reassigned to monthly or as-needed regimens. Outcomes were evaluated at 2 years.
- There was no difference in visual acuity gain between ranibizumab and bevacizumab (bevacizumab-ranibizumab difference, −1.4 letters; 95% CI, −3.7 to 0.8). Monthly regimens resulted in greater visual acuity gain than as-needed regimens (difference, 2.4 letters; 95% CI, 4.8 to 0.1). The prevalence of retinal fluid was less in the ranibizumab and monthly regimens.
- Switching to an as-needed regimen after one year of a monthly regimen resulted in a greater decrease in vision and a lower proportion of patients without fluid when compared with patients who continued to receive monthly injections.
- Patients who received bevacizumab experienced a higher rate of serious adverse events than patients who received ranibizumab (39.9% vs. 31.7%). However, the significance of this finding is uncertain given the lack of specificity of the observed events with VEGF inhibition.
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Objective:
Randomized controlled trial comparing the efficacy and safety of intravitreal bevacizumab and ranibizumab administered as monthly or as-needed regimens at two years.
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STUDY DESIGN:
Multicenter, single-blind randomized controlled trial.
STUDY SUBJECTS
Major inclusion criteria:
- Age of 50 years or more, presence of untreated active CNV secondary to AMD, visual acuity between 20/25 and 20/320, and neovascularization, fluid, or hemorrhage under the fovea. Active CNV was defined as the presence of leakage demonstrated on fluorescein angiography and intraretinal, subretinal, or sub-RPE fluid as demonstrated on OCT.
RANDOMIZATION SCHEME AND INTERVENTIONS
Patients were initially assigned to one of four study groups based on drug (bevacizumab or ranibizumab) and dosing regimen (monthly or as-needed) using permuted block randomization. At 1 year, patients in the monthly groups were randomly reassigned to either monthly or as-needed treatment with no change in drug assignment.
RESULTS (2 years)
Study population
- 1,185 patients were enrolled in the study. Of these, 1,107 patients were followed up during year 2. Visual acuity scores at 2 years were available for 1,030 of these patients.
- No substantial differences in demographic characteristics were observed between groups.
Follow-up time
- 2 years from the beginning of the study
Treatment
- Maximum of 26 injections in the as-needed groups. Mean of 12.6 injections in the ranibizumab as-needed-ranibizumab group and 14.1 in the as-needed-bevacizumab group.
- Estimated 2-year drug cost ranged from $705 in the bevacizumab-as-needed group to $44,800 in the ranibizumab-monthly group.
Visual acuity end-points
- Mean visual acuity change: + 8.8 letters in the ranibizumab-monthly group; + 7.8 letters in the bevacizumab-monthly group; +6.7 letters in the ranibizumab-as-needed group; +5.0 letters in the bevacizumab as-needed group.
- Difference in mean improvement: bevacizumab relative to ranibizumab = -1.4 letters; as-needed relative to monthly = -2.4 letters.
- Visual acuity was lower and retinal thickness was greater in patients who were switched from monthly to as needed treatment at 1 year when compared with patients who continued monthly treatment.
Anatomic outcomes
- Mean retinal thickness was 29 μm less in patients treated monthly when compared with those treated as needed.
- The proportion of patients without fluid was greater in the ranibizumab and as-needed groups.
- Mean change in lesion area was least in the ranibizumab and as-needed groups.
- The proportion of eyes with newly-diagnosed geographic atrophy was greater in the monthly groups.
- Growth of choroidal neovascularization was less in patients treated monthly compared to those treated as needed.
Adverse Events
- There were no differences in the number of arteriothrombotic (4.7% in the ranibizumab group vs. 5.0% in the bevacizumab group) or venous thrombotic events (0.5% in the ranibizumab group vs. 1.7% in the bevacizumab group) between drug groups.
- Patients who received bevacizumab experienced a greater rate of serious systemic adverse events (39.9%) when compared to patients who received ranibizumab (31.7%). This difference persisted when events associated with systemic treatment with anti-vascular endothelial growth factor drugs were excluded (28.4% in the ranibizumab group vs. 34.5% in the bevacizumab group).
CONCLUSIONS
- The two-year results from the CATT trial demonstrate that while bevacizumab and ranibizumab may result in different anatomic outcomes, both drugs produce similar visual outcomes. Monthly regimens are generally superior to treatment as-needed.