Twice-daily NSAID relieves post-cataract inflammation

May 1, 2005

The FDA approval for marketing of bromfenac ophthalmic solution 0.09% (Xibrom, ISTA Pharmaceuticals) gives the topical medication the distinction of being the first nonsteroidal anti-inflammatory drug (NSAID) in the United States indicated for twice-daily instillation in the management of ocular inflammation after cataract surgery.

The FDA approval for marketing of bromfenac ophthalmic solution 0.09% (Xibrom, ISTA Pharmaceuticals) gives the topical medication the distinction of being the first nonsteroidal anti-inflammatory drug (NSAID) in the United States indicated for twice-daily instillation in the management of ocular inflammation after cataract surgery.

Bromfenac ophthalmic solution has been on the market in Japan since 2000, where its cumulative use has reached about 2.8 million doses. That experience-combined with results from U.S. FDA clinical trials-supports the conclusion in late March that topical bromfenac 0.09% offers safe, effective, and well-tolerated anti-inflammatory therapy.

The phase III research program consisted of two identically designed, multicenter, double-masked, parallel placebo-controlled trials randomly assigning 527 patients 2:1 to twice-daily treatment with bromfenac or placebo for 14 days. Eligibility was determined on postoperative day 1 after patients underwent cataract surgery by phacoemulsification with IOL implantation.

To be included in the study, patients had to have significant inflammation as defined by the Summed Ocular Inflammation Score (SOIS) for anterior chamber cells and flare that was ≥3. To determine the SOIS, investigators independently graded the severity of anterior cells and flare using a standardized scale. Adding the grades for cells and flare together provided the Summed Ocular Inflammation Score.

Patient visits were conducted during the treatment phase on postoperative days 3, 8, and 15. Two additional post-treatment visits were scheduled on postoperative days 22 and 29. Rescue medication was allowed at the investigator's discretion based on judgment of resolution of the ocular inflammation. In the studies, 38.6% of placebo- and 10.4% of bromfenac-treated patients required alternative anti-inflammatory medications.

The proportion of patients achieving complete resolution of inflammation (SOIS = 0) by postoperative day 15 represented the primary efficacy endpoint. For that outcome, statistical significance favoring bromfenac was achieved by the first treatment visit (postoperative day 3) and was maintained at each subsequent visit throughout the study.

At baseline, the mean SOIS score in both study groups was identical, at 3.7. On postoperative day 3, 8% of bromfenac-treated patients and 1% of placebo-treated patients achieved a SOIS = 0. Corresponding rates for the two treatment groups at later visits were 35% and 14%, respectively, on postoperative day 8, and 59% and 27%, respectively, at the end of treatment.

Efficacy was also analyzed using SOIS data collected in the absence of use of other anti-inflammatory medications by evaluating the subject's last SOIS prior to the instillation of any rescue medication. Again, statistical significance favoring the bromfenac-treated group was achieved at each treatment visit, including the first visit (day 3, postoperatively).

Other measures were analyzed as secondary efficacy endpoints including:

For each of those measures at each treatment visit, the results showed superiority of bromfenac versus placebo (p < 0.05). For example, at day 15, 85% of bromfenac-treated patients compared with 53% of controls achieved an SOIS of 1.