Clinical Studies:
HORIZON
Citation: Singer MA, Awh CC, Sadda S, et al. HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology 2012; 119: 1175-1183.
Key Points
- HORIZON was an extension study of 24 months duration after completion of the 24-month MARINA, ANCHOR, or FOCUS trials of ranibizumab versus photodynamic therapy (PDT) for choroidal neovascularization (CNV) from age-related macular degeneration (AMD)
- Subjects were treated with ranibizumab at the investigating clinician’s discretion
- Visual acuity decreased in all groups. In eyes treated initially with ranibizumab in the clinical trials, visual acuity decreased such that all the visual gains from the trials were lost by the end of the study. In eyes initially in the control group, treatment with ranibizumab in the HORIZON trial period resulted in visual acuity loss, but at a lower rate than during control therapy in the trials
- The poor visual outcomes in this study likely reflect undertreatment (versus natural longer-term progression of the disease), given that significant AMD activity was noted (>30% with progression of AMD), but ranibizumab injection frequency was low (mean 4-5 ranibizumab injections per patient over 24 months)
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Objective
Extension study to evaluate long-term outcomes after intravitreal ranibizumab for AMD amongst patients who completed the MARINA, ANCHOR, or FOCUS* trial.
*In the FOCUS trial, all patients received PDT (no ranibizumab-only arm)
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STUDY DESIGN
Open-label, multicenter, extension study of the MARINA, ANCHOR, FOCUS trials
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Duration
24 months (after completion, i.e. 24 months, of MARINA, ANCHOR, FOCUS trial)
STUDY SUBJECTS
- completion of the MARINA, ANCHOR, or FOCUS trial through 24 months and potential need for addition anti-VEGF treatment
Major Inclusion criteria:
Study INTERVENTIONS
- Retreatment at the investigator’s discretion with ranibizumab 0.5mg (≥30 day intervals). No pre-defined treatment criteria.
Those initially treated with ranibizumab at the initial trial compared to “ranibizumab cross-over” (those treated with control in the initial trial and eligible for ranibizumab upon HORIZON baseline). Data presented relative to initial study baseline (month 0) and HORIZON baseline (month 24)
- Protocol-mandated examination q6 months; additional exams per investigator discretion
- Termination of study involvement (data counted up until that point) if PDT, pegaptanib, laser, or surgery performed for AMD, or if avastin used in either eye
RESULTS
Study population
- 853 subjects (of 1064 who had completed ANCHOR, MARINA, FOCUS trials)
- Study completion was for HORIZON was 84%, 68%, and 15% for year 1,2,3 (year 3,4,5 including the preceding trial)
- Those who enrolled in HORIZON had better VA and anatomical outcomes from the preceding trial than those that did not
Visual acuity end-points
- Mean visual acuity
- From month 0 (initial study baseline) to month 24 (HORIZON baseline): +9.0 letters ranibizumab initial, -9.6 controls
- From month 24 (HORIZON baseline) to month 60: -9.1 letters ranibizumab initial, -6.5 letters controls (ranibizumab cross-over)
- From month 0 (initial study baseline) to month 60: -0.1 letters ranibizumab initial, -16.1 letters controls (ranibizumab cross-over)
- Loss of < 15 letters
- From month 0 (initial study baseline): 20% ranibizumab initial, 47% controls (ranibizumab cross-over)
- From month 24 (HORIZON baseline): 25% ranibizumab initial, 15% controls (ranibizumab cross-over)
- Gain of > 15 letter
- From month 0 (initial study baseline): 23% ranibizumab initial, 7% controls (ranibizumab cross-over)
- From month 24 (HORIZON baseline): 3% ranibizumab initial, 6% controls
Mean number of injections
- From month 24 (HORIZON) to end of study: 4.4 (ranibizumab-initial), 4.8 (ranibizumab cross-over), 0 (ranibizumab untreated)
Anatomic outcomes
- Progression of AMD: 37% (ranibizumab-initial), 32% (control/ranibizumab cross-over), 8% (control/ranibizumab-untreated)
- Retinal hemorrhage: 28% (ranibizumab-initial), 35% (control/ranibizumab cross-over),10% (control/ranibizumab-untreated)
CONCLUSIONS
- During years 1-3 of the HORIZON extension study (after 24 months in the ANCHOR, MARINA, or FOCUS clinical trials), with investigator-discretion AMD treatment, ranibizumab injection frequency was low and high rates of AMD progression with significant vision loss was noted, with reversal of vision gains noted in the initial studies