COMMENTARY

Ranibizumab for AMD: Dose and Frequency

Vaidehi S. Dedania, MD; Sophie J. Bakri, MD

Disclosures

December 17, 2013

In This Article

Study Findings

The primary endpoint consisted of 3 comparisons: a superiority comparison (2.0 mg monthly vs 0.5 mg monthly) and 2 noninferiority comparisons (2.0 mg PRN and 0.5 mg PRN vs 0.5 mg monthly). The primary endpoint was not met, because there was no evidence that the 2.0-mg monthly dosing regimen was superior to the 0.5-mg monthly regimen (P = .8145).

A 4-letter noninferiority margin was established, which was not met when the 0.5 mg PRN and 2.0 mg PRN dosing regimens were compared with the 0.5 mg monthly regimen. Although the aforementioned primary endpoints were not met, a significant and clinically meaningful increase in BCVA at 12 months was demonstrated in all 4 treatment groups (Table).

Table. HARBOR Study Findings at Month 12

Endpoint 0.5 mg
Monthly
(n = 275)
0.5 mg
PRN
(n = 275)
2.0 mg
Monthly
(n = 274)
2.0 mg
PRN
(n = 273)
Mean gain in BCVA 10.1 8.2 9.2 8.6
Patients gaining ≥ 15 letters (%) 34.5 30.2 36.1 33
Patients losing < 15 letters (%) 97.8 94.5 93.4 94.9
Patients with Snellen VA ≥ 20/40 (%) 52.4 46.2 50 43.6
Patients with Snellen VA ≤ 20/200 (%) 7.3 8.4 11.3 12.1
Mean number of injections 11.3 7.7 11.2 6.9
Mean reduction in central foveal thickness (µm) 172 161.2 163.3 172.4

BCVA = best-corrected visual acuity; PRN = as-needed; VA = visual acuity

During the 12-month course of the study, no new safety events were identified. The most common ocular adverse event among all 4 treatment groups was conjunctival hemorrhage, at an overall rate of 19%. Although there were no serious ocular serious adverse events of glaucoma or increased intraocular pressure (IOP), episodes of increased IOP were seen, with postdose IOP ≥ 30 mm Hg in 3.7% (0.5 mg monthly group), 1.5% (0.5 mg PRN group), 2.6% (2.0 mg monthly group), and 1.9% (2.0 mg PRN group) of patients. No increase in IOP-related events was seen at higher doses of ranibizumab or in mean change from predose IOP to the 12-month measurement.

Rates of arterial thromboembolic events were low: 4.4%, 1.5%, 2.2%, and 2.9% of patients in the 0.5 mg monthly, 0.5 mg PRN, 2.0 mg monthly, and 2.0 mg PRN groups, respectively. Furthermore, the overall rates of nonfatal cerebrovascular accidents and central nervous system-related bleeding events were similar among the 4 treatment groups. No dose-related (0.5 mg vs 2.0 mg) or exposure-related (monthly vs PRN) trends in adverse events were observed.

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