Difluprednate effectiveness is evaluated when administered four times daily

June 1, 2009

Difluprednate ophthalmic emulsion 0.05% (Durezol, Sirion Therapeutics) was at least as effective as prednisolone acetate suspension 1% (Pred Forte, Allergan), dosed twice as often, in the treatment of endogenous anterior uveitis. Equivalent effectiveness with less-frequent dosing could improve patient compliance, according to one ophthalmologist.

Key Points

Fort Lauderdale, FL-In a multicenter study, difluprednate ophthalmic emulsion 0.05% (Durezol, Sirion Therapeutics) dosed four times a day for 14 days was at least as effective as the gold standard for treatment of endogenous anterior uveitis, prednisolone acetate suspension 1% (Pred Forte, Allergan) dosed eight times a day, according to findings presented during the annual meeting of the Association for Research in Vision and Ophthalmology.

"Difluprednate four times a day was equivalent to [prednisolone] eight times a day, or maybe even a little bit better," said Robert J. DaVanzo, MD, an ophthalmologist in private practice in High Point, NC, and an investigator in several clinical trials of difluprednate. In this double-masked, noninferiority trial, study visits were scheduled at days 3, 7, 14, 21, and 28, and at some of those time points, difluprednate was superior to prednisolone, Dr. DaVanzo said.

"Also, the symptomatology was reduced slightly more with [difluprednate] than it was with [prednisolone], although it wasn't a statistically significant difference," he said.

Difluprednate was approved by the FDA last summer for the treatment of inflammation and pain associated with ocular surgery. The FDA has accepted Sirion's supplemental new drug application seeking approval for difluprednate to be used to treat endogenous anterior uveitis.

Uveitis study, population

In the recent uveitis study, 90 subjects were randomly assigned 1:1; both groups were treated with the test agent for 14 days, followed by 2 weeks of tapering at half the dose and a 2-week follow-up period.

Subjects aged 2 or more years with endogenous anterior uveitis in at least one eye and more than 10 cells and a flare score of ≥ 2 in the anterior chamber (AC) of the same eye were eligible for participation. The average age of patients was 46.5 years in the difluprednate group and 42.9 years in the prednisolone arm. The cohort was 54% female and also was stratified by race and iris color.

Investigators evaluated symptomatology (pain, redness, and photophobia), visual acuity, the number of cells in the AC, the degree of flare, and hyperemia associated with uveitis. The primary endpoint was the difference from baseline in AC cell grades between the treatment groups. Grading criteria also were applied to AC flare, signs of inflammation, and symptoms.

Study, safety results

At day 14, difluprednate achieved a mean cell grade reduction of 2.1 versus 1.9 for prednisolone. A greater percentage of patients treated with difluprednate had an AC cell grade of 0 (≤ 1 cell) than those treated with prednisolone on day 14 (69% versus 62%, respectively). Patients in the difluprednate group also had a greater reduction in the mean pain score (71% versus 64%) than those in the prednisolone group at day 7 as well as a greater reduction in mean total sign score (6.5 versus 6.1) at day 14.

Reviewing the safety results, Dr. DaVanzo noted that no statistically significant difference was found in the incidence of elevated IOP between the two agents. Researchers had been concerned that difluprednate, a strong steroid, would cause more cases of ocular hypertension, but this did not occur. The rate of clinically significant IOP increase was 6% in the difluprednate group and 5% in the prednisolone group.

He also reported that no patients in the difluprednate treatment arm were withdrawn from the study because of lack of efficacy or worsening of symptoms, whereas five (12.5%) from the prednisolone group left the study for those reasons (p = 0.01).

Dr. DaVanzo also anecdotally described several patients with anterior uveitis whom he has treated with difluprednate. The first patient has had recurrent anterior uveitis every 6 months for several decades. His first episode in 2008 was treated with prednisolone every hour and sub-Tenon's triamcinolone acetonide 40 mg/ml (Kenalog, Bristol-Myers Squibb); the medications were taken for 30 days before the inflammation was under control.

Difluprednate was available when this patient was seen again in the fall due to another flare-up. After single-drug therapy for 15 days, the inflammation was controlled, Dr. DaVanzo said.

A second patient, who was part of the study, had his symptoms controlled in 13 days with difluprednate administered four times a day. When he had a recurrence later in the year, however, the study was over and the drug was not available because it had not yet been approved by the FDA. Thus, the patient received conventional therapy consisting of hourly prednisolone and prednisone by mouth up to 40 mg a day; he was treated in this way for 33 days before the uveitis was controlled.

"I'm really amazed at the results for these patients," Dr. DaVanzo concluded. "It's so much easier to take something four times a day. Also, although the study showed that difluprednate might be slightly better than prednisolone, I found that in certain patients the difference was remarkable."