Randomized pilot study suggests possible role for bromfenac treatment in exudative AMD
Results of a prospective, randomized pilot study suggest that a topical nonsteroidal anti-inflammatory drug (NSAID), bromfenac 0.09% (Xibrom, ISTA Pharmaceuticals), may be a useful addition to an anti-vascular endothelial growth factor (VEGF) agent, intravitreal ranibizumab (Lucentis, Novartis/Genentech), in patients being treated for exudative age-related macular degeneration (AMD).
Recently published on-line (Retina 20 Aug 2011; Epub ahead of print), the study was a multi-investigator, open-label, single-institution clinical trial conducted at the Casey Eye Institute, Oregon Health & Science University, Portland. It randomly assigned 30 consecutively enrolled eyes with new or recurrent exudative AMD 2:1 to combination therapy with ranibizumab 0.5 mg and bromfenac or to ranibizumab alone. All patients received monthly ranibizumab injections for 4 months. They were followed at monthly intervals and were re-treated with ranibizumab based on protocol-specified clinical and optical coherence tomography (OCT) criteria. Patients in the combination group used bromfenac twice daily.
At the primary endpoint at 12 months, no safety concerns were identified for the combination regimen, noted Dr Christina J. Flaxel, professor of ophthalmology, Casey Eye Institute.
"There is interest in identifying strategies for improving responses to intravitreal ranibizumab and reducing the frequency of injections," Dr Flaxel said. "Considering its anti-inflammatory activity and retinal bioavailability with topical administration, bromfenac is an attractive alternative.
"Although the combination regimen had no benefit for improving functional outcomes or decreasing the injection burden in this small study, the anatomic benefit is encouraging and suggests further investigation is warranted," she said. "We are now collaborating with the manufacturers of the two medications and hope to launch larger multicentre, randomized, controlled trials in the future."
To be enrolled with recurrent exudative AMD, patients were required to have achieved lesion closure with previous treatment and to have received no therapy within the previous 3 months. Any eye that had prior photodynamic therapy or focal laser therapy was excluded. Patients were allowed to continue oral AREDS supplements and other medications and standard treatments.
Patients had a mean age of about 80 years. Baseline mean ETDRS letter score was 52.8 for the combination group and 60.1 in the monotherapy group; mean CMT was 288 and 225 μm, respectively. The distribution of patients with recurrent versus new exudative AMD was 3:1 in the combination arm and 1:1 in the ranibizumab arm. None of the between-group differences in baseline characteristics was statistically significant.
Re-treatment criteria were modelled after those used in the Comparison of AMD Treatments Trials and considered loss of visual acuity, presence of hemorrhage on clinical exam, and OCT evidence of retinal/subretinal fluid. Mean number of injections administered during the 12-month study period was nearly identical in the combination and ranibizumab groups, 7.16 and 6.80.
In addition, at 12 months, both groups achieved nearly a 4-letter gain from baseline ETDRS BCVA. There were also no statistically significant differences between groups in BCVA change from baseline at 4 or 6 months.
At 12 months, CMT was reduced from baseline by an average of 81.6 μm in the combination group and 42.5 μm in the ranibizumab group. The change in both groups was statistically significant, but the between-group comparison also showed statistical significance. In addition, a significantly greater proportion of patients in the combination group compared with the controls achieved a CMT reduction of at least 50 μm.
"Any potential clinical significance of the difference in CMT reduction between groups is unclear, but [we hope] we will be better able to answer this question in larger, multicentre, randomized, controlled trials," Dr Flaxel said.
The safety analysis showed burning/stinging and other local irritation-type events occurred more often in patients using bromfenac compared with the controls. However, the severity ratings were no worse than mild and no patient discontinued bromfenac because of intolerance.
Dr Christina J. Flaxel is professor of ophthalmology at the Casey Eye Institute, Portland, Oregon, USA. She can be contacted by E-mail: email@example.com
Dr Flaxel has no financial interest in the subject matter.