Safety and efficacy of ripasudil in Japanese patients with glaucoma or ocular hypertension: 12-month interim analysis of ROCK-J, a post-marketing surveillance study

Hidenobu Tanihara,Ryoji Gunji,Tetsuro Sano,Takahiko Kakuda,Takashi Kanno

doi:10.1186/s12886-020-01490-1

Hidenobu Tanihara, Ryoji Gunji + Show 3 more

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https://doi.org/10.1186/s12886-020-01490-1

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Journal: BMC Ophthalmology	Publication Date: Jul 9, 2020
Citations: 25	License type: open-access

Affiliation: Kumamoto University Hospital, Kowa (Japan)

Abstract

BackgroundRipasudil is approved in Japan for glaucoma or ocular hypertension (OH) when other treatments are ineffective or cannot be administered. Its long-term safety and efficacy are being examined in a post-marketing surveillance study; 12-month data are described here.MethodsThis prospective, open-label, observational study enrolled patients with glaucoma or OH who started ripasudil during routine care. The key safety outcome was the incidence of adverse drug reactions (ADRs), focusing on allergy and/or inflammation-related ADRs such as blepharitis (including allergic) or conjunctivitis (including allergic). The primary efficacy endpoint was least squares mean (LSM) ± standard error (SE) change in intraocular pressure (IOP) from baseline to 12 months in all patients and in diagnostic groups. Secondary endpoints were change in IOP in groups stratified by treatment initiation pattern, number of concomitant drugs, and baseline IOP.ResultsOverall, 3359 patients (48% male, mean age ± standard deviation [SD] 69.1 ± 12.7 years) were evaluated for safety and 3323 for efficacy. Diagnoses were primary open-angle glaucoma (43.9%), normal-tension glaucoma (36.6%), secondary glaucoma (8.7%), OH (4.2%), and primary closed-angle glaucoma (2.4%). Mean ± SD observation period was 300.1 ± 122.4 days; 1010 patients (30.1%) discontinued ripasudil by 12 months. ADRs occurred in 626 patients (18.6%); the most common were conjunctival hyperemia and blepharitis. Allergy and/or inflammation-related ADRs occurred in 388 patients (11.6%), most commonly blepharitis (5.6%) and conjunctivitis (4.2%). IOP decreased significantly from a mean ± SD 18.1 ± 6.1 mmHg at baseline; the LSM ± SE IOP change throughout 12 months of ripasudil treatment was − 2.6 ± 0.1 mmHg (− 14.0 ± 0.4%; p < 0.001). A significant decrease in IOP at 12 months was seen in all categories of baseline IOP (p < 0.001), and all types of glaucoma (p < 0.001), except neovascular glaucoma. Ripasudil was associated with a significant reduction in IOP at 12 months whether initiated as monotherapy or in combination with ≤4 concomitant glaucoma therapies (p < 0.001).ConclusionsRipasudil was safe and effective in patients with glaucoma or OH during routine care. No new safety signals were identified, and significant reductions in IOP were maintained over 12 months.

Highlights

Ripasudil is approved in Japan for glaucoma or ocular hypertension (OH) when other treatments are ineffective or cannot be administered
3359 patients were included in the safety analysis set, and 3323 patients were included in the efficacy analysis set (Fig. 1)
Our results confirm the earlier results from the 3-month interim analysis of this post-marketing surveillance (PMS) study [18], showing that ripasudil is effective in lowering intraocular pressure (IOP) across a range of patients, and that the lack of safety issues seen during short-term treatment is true during treatment for 12 months

Summary

Introduction

Ripasudil is approved in Japan for glaucoma or ocular hypertension (OH) when other treatments are ineffective or cannot be administered. According to estimates published in 2014, between 64 and 70 million people globally are affected by glaucoma [1, 2], but as this is a condition associated with aging, the prevalence of glaucoma is estimated to increase to 76 million in 2020 and to more than 111 million by 2040 [2]. In Japan, the estimated prevalence of glaucoma is 5.0% in people ≥40 years of age [3]. International guidelines, including the Japan Glaucoma Society Guidelines for Glaucoma (fourth edition) [4], the American Academy of Ophthalmology Preferred Practice Patterns guideline [5], and guidelines from the National Institute of Health and Care Excellence in the UK [6], recommend prostaglandins as the initial medical therapy for primary openangle glaucoma (POAG) and ocular hypertension (OH). In the Japanese guidelines, β-blockers may be used in first-line treatment, but should be selected with due attention to contraindications and risk of adverse drug reactions (ADRs); the recommended second-line treatments are carbonic anhydrase inhibitors, α2 agonists, Rho-associated protein kinase (ROCK) inhibitors, α1 blockers, ion-channel openers, nonselective nerve stimulants, or parasympathetic nerve stimulants [4]

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