Difluprednate 0.05% versus prednisolone acetate 1% for endogenous anterior uveitis: a phase III, multicenter, randomized study

Abstract

Purpose: Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition.

Methods: This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily, alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54) eight times daily. The 14-day treatment period was followed by a 14-day dose-tapering period and a 14-day observation period. The primary efficacy end point was change in anterior chamber cell grade (range, 0 for ≤1 cell to 4 for >50 cells) from baseline to day 14.

Results: At day 14, the mean change in anterior chamber cell grade with difluprednate was noninferior to that with prednisolone acetate (-2.2 vs. -2.0, P = 0.16). The proportions of difluprednate-treated patients versus prednisolone acetate-treated patients demonstrating complete clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate-treated patients, P = 0.0013) but not at other time points. The mean IOP values in both groups remained less than 21 mm Hg throughout the study.

Conclusions: Difluprednate 0.05% four times daily is well tolerated and is noninferior to prednisolone acetate 1% eight times daily for the treatment of endogenous AU. (ClinicalTrials.gov number, NCT01201798.).

Keywords: acute anterior uveitis; corticosteroid; difluprednate; endogenous anterior uveitis; intraocular pressure; noninfectious uveitis; prednisolone; prednisolone acetate; uveitis.

Figures

Figure 1

Study flow diagram. *One patient was randomized to receive difluprednate 0.05% and was treated with prednisolone acetate 1%. This individual was included in the intent-to-treat population as randomized (difluprednate) and in the safety population as treated (prednisolone acetate) and was excluded from the per-protocol population.

Figure 2

The mean change from baseline in anterior chamber cell grade in patients receiving difluprednate 0.05% dosed four times daily (n = 46) or prednisolone acetate 1% dosed eight times daily (n = 47) (per-protocol population with LOCF). Filled data labels represent the results for the primary efficacy end point. The mean (SD) changes in anterior chamber cell grade from baseline to day 14 were −2.2 (1.0) with difluprednate and −2.0 (1.0) with prednisolone acetate (P = 0.16; mean difference, −0.22 [favoring difluprednate]). Hollow data labels represent the secondary efficacy outcomes. Error bars denote SD. The dosing schedule does not include placebo doses, which were interspersed with difluprednate drops to maintain masking. Anterior chamber cell grade was based on a five-point scale ranging from 0 (≤1 cell) to 4 (≥50 cells).

Figure 3

Proportion of patients achieving grade 0 anterior chamber cells (≤1 cell per high-power field) (A) and with complete clearing of anterior chamber cells (i.e., achieving zero cells) (B) during the study (per-protocol population with LOCF). *P = 0.021; **P = 0.046; ***P = 0.013.

Figure 4

Intraocular pressure change from baseline in study eyes (safety population). *P = 0.0013 (difluprednate 0.05% [diamonds] versus prednisolone acetate 1% [squares]). Error bars denote SD.

Figure 5

Proportion of patients with increased IOP from baseline (safety population). (A) Increase of at least 5 mm Hg. (B) Increase of at least 8 mm Hg. (C) Increase of at least 10 mm Hg. (D) Increase of at least 10 mm Hg and an overall pressure of at least 21 mm Hg.