Clinical Studies:
PIER
Citation: Abraham P, Yue H, Wilson L. Randomized, double-masked sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 2. American Journal of Ophthalmology 2010; 150: 315-324.
Key Points
- BOLT was a randomized, controlled, clinical trial that evaluated quarterly dosing of ranibizumab 0.3mg or 0.5mg versus sham for choroidal neovascularization (CNV) from age-related macular degeneration (AMD)
- Ranibizumab 0.3mg and 0.5mg monthly x 3 and then quarterly produced significantly better visual outcomes compared to sham, but the visual outcomes were worse than those previously reported in clinical trials for monthly ranibizumab for AMD
- Additional visual benefit was attained by switching to monthly ranibizumab injection late in year 2.
- Delayed switching to ranibizumab in the sham group (at 14 months or later) did not produce significant visual benefit
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Objective
To study the efficacy of ranibizumab monthly and then quarterly for AMD
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STUDY DESIGN
Phase 3, multicenter, randomized, double-masked, sham-controlled trial
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DURATION
24 months
STUDY SUBJECTS
- subfoveal CNV from AMD (any type; if occult, needed signs of disease progression—10% increase in lesion size on FA; ≥ 5 letter vision loss; or retinal hemorrhage)
Major inclusion criteria:
- Central foveal fibrosis or atrophy
- Subfoveal hemorrhage ≥ 1 disc area of ≥ 50% total CNV lesion size
Major exclusion criteria:
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized 1:1:1 to
(a) ranibizumab 0.3mg
(b) ranibizumab 0.5mg
(c) sham injection
Treatment - monthly x 3, then q3 months
Amendments:
- After ANCHOR/MARINA data, amendment allowed sham group to receive q3mth ranibizumab 0.5mg after the 12 month visit
- After the 12-month PIER data, amendment to allow all patients the opportunity to switch to monthly ranibizumab 0.5mg
RESULTS (24 months)
Study population
- 184 subjects
- 80% had occult or minimally classic CNV (occult was higher in ranibizumab groups than in control groups (50% vs <33%)
- Study completion was sham 73%, ranibizumab 0.3mg 88%, 89% ranibizumab 0.5mg
Treatment results
- At the time of the crossover amendment, 64% of the sham group crossed over to ranibizumab quarterly
- At the time of the amendment for monthly ranibizumab, 54% of the sham subjects, 72% of the ranibizumab 0.3mg, and 72% of the ranibizumab 0.5mg subjects switched to monthly ranibizumab
Visual acuity end-points (24 months)
- Loss of < 15 letters: 41% sham, 78% ranibizumab 0.3mg, 82% ranibizumab 0.5mg
- Gain of > 15 letter: 5% sham, 15% ranibizumab 0.3mg, 8% ranibizumab 0.5mg (no statistically significant difference)
- Mean VA change: sham -21.4 letters, -2.2 letters ranibizumab 0.3mg, -2.3 letters ranibizumab 0.5mg
Angiographic end-points
- Total CNV area on FA: +1.9 disc area (DA) sham, +0.29 DA ranibizumab 0.3mg, +0.64 DA ranibizumab 0.5mg
Crossover of sham group to ranibizumab
- 39 of 40 eligible sham patients rolled, over at month 14 (39%), 17 (43%), or 20 (18%). Visual acuity continued to decrease until study completion in this group
*Statistical analysis unable to be performed to compare groups due to small sample sizes*
Rollover to monthly ranibizumab (for all groups)
- In all groups, an average of approximately 2.5 injections were received after rollover to monthly ranibizumab (i.e. towards the end of the 24 month period)
- Average visual acuity increased in all groups after roll-over
*Statistical analysis unable to be performed to compare groups due to small sample sizes*
CONCLUSIONS
- Ranibizumab 0.3mg and 0.5mg monthly x 3 then quarterly produced significantly better visual outcomes, compared to sham, although the visual outcomes appear worse than those previously reported in trials of monthly ranibizumab