Efficacy and safety of 0.05% cyclosporine ophthalmic emulsion in treatment of Chinese patients with moderate to severe dry eye disease: A 12-week, multicenter, randomized, double-masked, placebo-controlled phase III clinical study

Background: Dry eye disease (DED) is a chronic ocular surface disease that affects hundreds of millions of people worldwide. Although 0.05% cyclosporine ophthalmic emulsion (CsA OE) has long been prescribed in the U.S. for the treatment of DED, it is not commercially available in China. Our study aims to compare the efficacy and safety profile of 0.05% CsA OE versus vehicle in Chinese patients with moderate to severe DED. Methods: This was a multicenter, randomized, double-masked, 2-parallel-arm, 3-month phase III study. Patients with moderate to severe DED were randomized to receive twice-daily 0.05% CsA OE or its vehicle, along with unpreserved hypromellose eye drops 3 times per day. Patients were followed up at day 7, 28, 56, and 84, as well as 2 weeks after the medications were discontinued for safety assessment. Results: A total of 240 patients were randomized. The overall effective rate (OER) and efficacy index were significantly better in the CsA OE than vehicle group at all follow up times (all P<.05), and the OER of CsA OE and vehicle group at month 3 was 70.6% and 27.8%, respectively (P<.001) (primary endpoint). The patients in CsA OE group displayed a significant improvement in dry eye symptoms from day 28 and ocular surface test results from day 7 (all P<.05). The ocular surface disease index scores of 0.05% CsA OE treated patients were significantly better than those treated with vehicle control at day 56 and 84 (P=.0061 and <.001, respectively). Drug related adverse events (AEs) were recorded in 6(5%) and 3(2.5%) patients in the CsA OE and vehicle groups respectively (P=.4061) with ocular pain as the most frequently reported AEs, and it was mostly mild to moderate. There were no detrimental effects on visual acuity, intraocular pressure, or vital signs. Conclusions: Twice-daily instillation of 0.05% CsA OE was effective and well tolerated for the treatment of moderate to severe DED in Chinese population during the 3 months of the study.