Anterior Segment Cataract Figure 1: Structure of Bromfenac
Table 1: Comparison of BCVA and ETDRS Letters Scores in Bromfenac- and Nepafenac-treated Patients
O ||
Br C Time Pre-operative (baseline) H2 NCH2
Bromine halogenation: • Is highly lipophilic = rapid, sustained levels in ocular tissues7 • Results in high degree of penetration and potency
Clinical significance of in vitro data is unknown.
Figure 2: Bromfenac Pivotal Trial Results – Proportion of Patients with Zero-to-Trace Inflammation (0-5 cells with 0 Flare)
70 80
10 20 30 40 50 60
0 BROMDAY By day 15 p<0.0001.
These results are comparable to the findings of the integrated analysis. Zero-to-trace inflammation is defined as (0-5 cells with 0 flare). Note that the study protocol does not allow the use of corticosteroids. Source: Silverstein SM et al., 2011.5
Figure 3: Bromfenac Pivotal Trial Results – Proportion of Patients Reporting No Pain
100
20 40 60 80
0 Day 1 Day 3 Bromfenac (n=230) * p<0.0001.
The difference between bromfenac and placebo was statistically significant at day 1 and remained so throughout the study. At day 15, nearly 95 % of bromfenac-treated patients were pain-free, compared with only 70.5 % of placebo-treated patients. The median time to pain resolution for bromfenac was half that for placebo – two days versus four days. Source: Silverstein SM et al., 2011.5
38 Day 8 Placebo (n=225) Day 15
87.0 % *
64.7 % * * * 94.8 % 70.5 % PLACEBO
An integrated data set, composed of this pivotal data, a phase II dosing study and an additional phase III placebo-controlled study, showed consistent results across all study endpoints in a much larger group of patients – i.e., 872 subjects. This integrated data set showed earlier statistical significant in the percentage of patients who achieved an SOIS of 0, which was reached at day 8 rather than at day 15.
Safety and Tolerability
Bromfenac should be used with caution in patients with sulfite sensitivities and, like all NSAIDs, can cause slow or delayed healing, increased bleeding times, and cross-sensitivities with other topical NSAIDs. As a class, topical NSAIDs should be used with caution in patients with corneal compromise. In the bromfenac 0.09 % once-daily pivotal trials, adverse events were mild and occurred in 2–7 % of patients.5,6
By day 15 CO2 Na •1½H2 O
Post-operative Week 1 Week 3 Week 6
Bromfenac 0.09 % Nepafenac 0.1 % once-daily (n=10) tid (n=10)
43.3
51.3 50
49.1 46.6
52 49
48.3
BCVA = best corrected visual acuity; ETDRS = Early Treatment Diabetic Retinopathy Study; tid = three times a day. Source: Cable M, 2011.6
statistically significant at day 3, with a widening gap through to day 15.5 Bromfenac is the first and only topical NSAID to employ an ocular comfort grading scale as part of its pivotal data.
A statistically significant difference in pain was seen between the two groups at the first measurement on post-operative day 1. Bromfenac was significantly better than placebo at all time-points. At day 15, nearly 95 % of bromfenac-treated patients were pain-free, versus 70.5 % of patients in the placebo group (see Figure 3). The median time to resolution of pain in the bromfenac subjects was half that in the placebo patients, at two days versus four days. Bromfenac users scored their comfort experience as superior to that of placebo subjects in four of seven parameters, with the other three parameters being equivalently rated by the two groups.5
Regarding adverse events related to comfort (ocular discomfort, foreign body sensation, and eye pain), the occurrence was less than half in patients who received bromfenac compared with the placebo group, consistent with the analgesic effect of bromfenac.5
Reduced dosing schedules with bromfenac mean that ocular surfaces may benefit, as patients receive half the load of active medication and accompanying preservative.
Comparison of Bromfenac Once-daily with Nepafenac Three Times a Day after Cataract Surgery In the trial comparing bromfenac ophthalmic solution 0.09 % once-daily with nepafenac 0.1 % three times a day (tid) after cataract surgery,6
a small number of patients were randomized to receive US OPHTHALMIC REVIEW
Patients (%)
Patients (%)
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76