Clinical Studies:
CATT: Five-Year Outcomes
Citations: Maguire MG, Martin DF, Comparison of Age-related Macular Degeneration Treatments Trials Research Group, et al. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: The comparison of age-related macular degeneration treatment trials. Ophthalmology. 2016; 123(8): 1751-1761.
Key Points
- The CATT trial was a randomized controlled trial comparing the efficacy of bevacizumab and ranibizumab when administered on a monthly or 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.
- After 2 years, patients were released from the trial protocol. At 5 years, patients were asked to return for examination.
- At 5 years, mean visual acuity was 3 letters worse than at baseline and 11 letters worse than at 2 years.
- 50% of patients had a visual acuity of 20/40 or better and 10% had a visual acuity of 20/20 or better, while 20% had a visual acuity of 20/200 or worse.
- The proportion of eyes with an abnormally thin retina (<120 μm) and geographic atrophy increased from 2 years to 5 years. Mean lesion size increased by more than 50%.
- The proportion of eyes with retinal fluid decreased the greatest in the first year of treatment and remained relatively constant afterwards. More than 70% of eyes demonstrated retinal fluid at 5 years.
- Between years 2 and 5.5 years, patients originally assigned to ranibizumab lost more vision than patients originally assigned to bevacizumab. No other differences in visual acuity or morphologic outcomes were observed between regimen or drug groups.
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Objective:
Follow-up cohort study evaluating outcomes in patients enrolled in the Comparison of AMD Treatment Trials who returned 5 years after initiation of treatment with ranibizumab or bevacizumab.
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STUDY DESIGN:
Multicenter cohort study.
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. After 2 years, patients were released from the trial and at 5 years, patients were asked to return for examination. Patients who returned underwent a dilated fundus exam, refraction, visual acuity measurement, spectral-domain OCT, fundus color photography, and fluorescein angiography. Data on post-trial visits and treatments were also collected.
RESULTS (2 years)
Study population
- 914 patients alive at the end of the trial were alive at the time of the follow-up study. Visual acuity was available in the required interval of 4.3 years to 7.1 years for 647 patients. The mean interval between trial enrollment and the follow-up study visit was 5.5 years.
- Participants in the follow-up study were 2.3 years younger and had a greater mean visual acuity at baseline (3.1 letters) and at 2 years (5.4 letters) when compared with nonparticipants.
Follow-up time
- Mean of 5.5 years (range, 4.3 years to 7.1 years) after the date of original treatment assignment in the clinical trial.
Treatment
- The mean number of treatments between release from the clinical trial and follow-up was 15.4.
- After release from the clinical trial, more than half of the patients received a treatment other than the drug assigned to them in the clinical trial.
- 14.8% of patients received no treatment between the end of the clinical trial and the follow-up study visit.
Visual acuity end-points
- 49.6% of patients had a visual acuity of 20/40 or better at follow-up. 20% of patients had a visual acuity of 20/200 or worse.
- Mean change in visual acuity was -10.8 letters from year 2 and -3.3 letters from baseline.
- Patients assigned to ranibizumab lost more letters between 2 years and follow-up than patients assigned to bevacizumab.
- No differences in visual acuity were observed between dosing regimens.
Anatomic outcomes
- Mean total thickness at the fovea was 278 μm, representing a change of -20 μm from 2 years and -182 μm from baseline.
- The proportion of eyes with an abnormally thin retina (lt;120 μm) was 36% compared with 22% at 2 years.
- The proportion of eyes with geographic atrophy was 41% compared with 20% at 2 years.
- The proportion of eyes with subretinal (38%) and sub-RPE (36%) fluid was similar to the respective proportions at year 2. However, the percentage with intraretinal fluid (61%) was greater than at year 2 (50%).
- No differences in OCT measures were noted between drug or dosing regimens.
- The mean area of the total neovascular lesion increased from 2 years (8.1 mm2) to 5 years (12.9 mm2).
- The proportion of eyes with geographic atrophy increased from 20% to 41% at 5 years.
- No anatomic differences were observed between drug or dosing regimens.
Adverse Events
- Between the end of the clinical trial and follow-up, patients originally assigned to ranibizumab experienced more arteriothrombotic events than patients assigned to bevacizumab (7.6% vs. 4.5%). However, the significance of this is unclear given that the proportion of these events were nearly equal during the clinical trial.
- There were no other differences in the rates of death or serious medical events between groups.
CONCLUSIONS
- The CATT Follow-up Study demonstrates the long-term efficacy of anti-VEGF therapy, particularly with regards to preserving visual function in patients with AMD. Comparisons between dosing and drug regimens are limited since few patients continued to receive their originally-assigned drug or dosing schedule.