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Two phase III studies evaluated difluprednate 0.05% emulsion (Durezol, Sirion Therapeutics) for the treatment of significant inflammation after ocular surgery. The investigational agent was dosed twice and four times daily and compared with vehicle. Difluprednate acted quickly to reduce inflammation and pain and achieved significant differences compared with vehicle in the primary efficacy analysis and multiple secondary endpoints. No difference in mean IOP was found between study groups.
Chicago-Pivotal trial results demonstrate that twice-daily topical treatment with difluprednate, a novel corticosteroid, provides safe and rapidly effective control of inflammation after intraocular surgery, reported Michael S. Korenfeld, MD, at the annual meeting of the American Society of Cataract and Refractive Surgery.
Difluprednate 0.05% emulsion (Durezol, Sirion Therapeutics) was investigated in two identically designed phase III clinical trials that included a total of 438 patients. Participants were divided into four groups of equal size and randomly assigned to one of four treatment arms to receive difluprednate or vehicle twice a day or four times a day for 14 days. Treatment then was tapered for an additional 2 weeks. Eligible patients had to exhibit significant inflammation on the first day after surgery with an anterior chamber cell grade of 2 or greater (>10 cells).
Mean IOP remained within the normal range throughout the study. Few patients in any treatment group experienced a clinically significant increase in IOP. Less than 2.8% of patients in either difluprednate group and 0.9% of vehicle-treated controls met the criterion of having an observed value of 21 mm Hg or greater and a change from baseline of 10 mm Hg.
"Since inflammation can result in damage to ocular tissues, rapid resolution is an important goal. While corticosteroids are highly effective anti-inflammatory agents, current regimens involve frequent dosing that can compromise compliance and therefore efficacy," said Dr. Korenfeld, MD, assistant clinical professor of ophthalmology and visual sciences, Washington University in St. Louis.
"Difluprednate represents a welcome new anti-inflammatory option that is six times more potent than prednisolone according to standard corticosteroid assays," Dr. Korenfeld said. "The results from these phase III studies demonstrate that it acts quickly and is highly safe and effective in controlling inflammation with a convenient twice daily dosing regimen."
Patients aged 2 or more years were eligible for study enrollment, although mean patient age was almost 70 years. Most patients were being operated on for senile cataracts.
Secondary efficacy endpoints in the study compared study groups for changes from baseline in anterior chamber cell grade and count, proportions of patients achieving clinical cure (cell count of five or less and absence of flare), resolution of pain and photophobia graded with a Visual Analogue Scale, and resolution of signs of inflammation, including cell, flare, injection, edema, and keratitic precipitates.
By day three, 38% and 45% of patients in the difluprednate b.i.d. and q.i.d. groups, respectively, were pain-free compared with 25% of controls. The proportions of patients in whom that outcome was achieved increased in all groups with continued follow-up, and a significant difference favoring difluprednate treatment was maintained at days eight and 15.
At day 15, almost three-fourths of patients in each treatment group had clinical cure, compared with 27% of controls, and the inflammatory cell count was reduced nearly 90% in the difluprednate groups compared with baseline. An anterior chamber cell grade of 0 was achieved in 56% of patients in the difluprednate b.i.d. group, 63% of patients in the difluprednate q.i.d. group, and 16% of controls by day 15.