Long-Term Intraocular Pressure-Lowering Effects and Adverse Events of Ripasudil in Patients with Glaucoma or Ocular Hypertension over 24 Months.

ABSTRACT

INTRODUCTION: Glaucoma is a leading cause of irreversible blindness and ripasudil was the first Rho kinase inhibitor approved as antiglaucoma medication. Here we present the final analysis of the ROCK-J study, a large-scale post-marketing surveillance study to evaluate the long-term safety and effectiveness of ripasudil in Japanese patients with glaucoma or ocular hypertension in a real-word clinical setting. METHODS: ROCK-J was a 24-month, prospective, open-label, observational study that included ripasudil-naïve patients with glaucoma or ocular hypertension who were initiating treatment with ripasudil according to the Japanese approved indication between June 1, 2015 and April 30, 2017. The primary safety endpoint was the incidence of adverse drug reactions (ADRs) (including blepharitis, plus assessment of its background factors); the primary efficacy endpoint was change in intraocular pressure (IOP) from baseline to 24 months. RESULTS: A total of 3374 Japanese patients with glaucoma or ocular hypertension were evaluated for safety and 3178 for effectiveness of ripasudil over a mean 524.5-day observational period. Overall, 853 (25.3%) patients experienced adverse drug reactions; the most common were blepharitis (8.6%), conjunctival hyperemia (8.5%), and conjunctivitis (6.3%). Multivariate analyses demonstrated that patients were more likely to experience the ADR blepharitis with ripasudil treatment if they were female (hazard ratio [HR] 1.307; p = 0.040), had comorbid or a previous history of blepharitis (HR 2.178; p = 0.001), or had a history of allergy to pollen (HR 1.645; p = 0.003) or medication (HR 2.276; p < 0.001). IOP decreased significantly from baseline with ripasudil; the least-squares mean ± standard error change in IOP from baseline to 24 months was - 2.6 ± 0.1 mmHg (p < 0.001). Significant IOP changes were seen in four types of glaucoma, namely primary open-angle glaucoma, normal-tension glaucoma, primary angle-closure glaucoma, and secondary glaucoma, and ocular hypertension. CONCLUSION: Ripasudil was safe and effective as an antiglaucoma medication with no new safety signals identified and significant reductions in IOP maintained over 24 months of treatment.