Clinical Studies:
SEVEN-UP
Citation: Rofagha S, Bhisitkul RB, Boyer DS, et al. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology 2013; 129: 2292-2299.
Key Points
- SEVEN-UP was a non-interventional study that evaluated very long-term (7 year) outcomes of ranibizumab treatment for choroidal neovascularization (CNV) from age-related macular degeneration (AMD) in patients who had been in the ranibizumab treatment groups and completed both the ANCHOR or MARINA and the HORIZON trials
- A single return evaluation was performed on all subjects, on average 7 years after entry into the original trials. Patients had been treated with ranibizumab as per the discretion of their treating clinician in the intervening years
- There was remarkable loss of vision noted at 7 years (-9 letters from entry into the original trial and -20 letters from peak vision in ANCHOR/MARINA trials, -7 letters from the conclusion of the HORIZON trial)
- These poor visual outcomes likely represent undertreatment given that, at the SEVEN-UP study visit, 68% of eyes had exudation on OCT, mean injections were 6.8 over 3.4 years, and 41% of eyes had not received any ranibizumab injections since exiting HORIZON
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Objective
Extension study to evaluate long-term outcomes after intravitreal ranibizumab for AMD amongst patients who completed the MARINA or ANCHOR trial and the subsequent HORIZON extension study
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STUDY DESIGN
Open label, multicenter, non-interventional cohort study
STUDY SUBJECTS
Major inclusion criteria:
- Completion in the ranibizumab-treatment arm (not controls) of the ANCHOR or MARINA trial (24 months) and subsequent completion of the HORIZON trial (≥ 24 months)
RANDOMIZATION SCHEME AND INTERVENTIONS
Subjects who met inclusion criteria were recruited for a return evaluation. Individual subject comparisons were obtained retrospectively from the ANCHOR, MARINA, HORIZON study databases.
RESULTS (24 months)
Study population
- 529 patients originally in the ranibizumab-treatment arms of ANCHOR/MARINA, of these 357 participated completion in HORIZON. 155 of these 357 subjects were eligible for SEVEN-UP from the 14 sites participating in SEVEN-UP, and 65 were enrolled (42% enrollment).
- No significant difference between SEVEN-UP baseline characteristics to baseline characteristics of the ranibizumab-treatment groups of ANCHOR/MARINA
Follow-up time
- 7.3 years from entry to ANCHOR/MARINA, 3.4 years from completion of HORIZON
Visual acuity end-points
- Mean visual acuity: -8.6 letters from entry into ANCHOR/MARINA; - 19.8 letters from peak vision upon completion of 24 months of monthly ranibizumab treatment in ANCHOR/MARINA; -6.9 letters from 24-month visit in HORIZON study
- Compared to entry in ANCHOR/MARINA, 66% stable or improved (12% with ≥ 15 letter gain; 54% stable), 34% with ≥ 15 letter loss
- Compared to time of exit from ANCHOR/MARINA, 15% with stable or improved vision, 85% worse
- Compared to the month 24 HORIZON measurement, 32% had stable or improved vision, 68% worse
Treatment
- Mean 6.8 injections over 3.4 years (2 injections/year) in the years after exiting HORIZON
- 41% of eyes received 0 injections
Anatomic outcomes
- 48% had definite or questionable leakage on FA at the SEVEN-UP study visit
- 68% of eyes had exudation (IRF/SRF) on OCT
- 98% had macular atrophy on FAF, 90% involving the fovea. Such atrophy was associated with worse vision
CONCLUSIONS
- In this retrospective study, approximately 7 years after entry into ANCHOR/MARINA, patients remain at significant risk of vision loss from AMD, with low injection frequencies and high rates of AMD activity noted