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

Abstract

Background: Ripasudil 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. Methods: This 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. Results: Overall, 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 inflammationrelated 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). Conclusions: Ripasudil 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.

The ROCK Inhibitor Ripasudil Shows an Endothelial Protective Effect in Patients With Low Corneal Endothelial Cell Density After Cataract Surgery

“…The safety of ripasudil is well established, and since 2014 it has been available in Japan for the treatment of glaucoma. 19 , 20 In the present study, we sought to assess whether ripasudil may have broader application in the clinic. We assessed this by using the ROCK inhibitor ripasudil in patients with glaucoma with low corneal endothelial cell density who were undergoing cataract surgery.…”

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function

“…Some ROCK inhibitors ( Table 4 ) have also been tested in all clinical trial phases for the treatment of glaucoma and ocular hypertension [ 369 ] and could play a role in the treatment of acute lung injury [ 370 ]. Three ROCK inhibitors that indirectly induce F-actin depolymerization through blocking the signaling pathway that leads to NMMII activity [ 371 ] are approved for clinical use: fasudil in Japan for the treatment of cerebral vasospasm (1995) [ 372 ]; ripasudil, also in Japan, for treatment of glaucoma (2014) [ 372 , 373 , 374 ]; and netarsudil, which was authorized in the US after FDA approval [ 375 ]. Fluvoxamine, which is a selective serotonin uptake inhibitor that inhibits actin polymerization, is approved as an anti-depressant [ 376 ].…”

“…Netarsudil is approved by the FDA for treatment of glaucoma or ocular hypertension in the US[375] 3. Ripasudil is approved for treatment of glaucoma or ocular hypertension in Japan[374] 4. Fluvoxamine is approved for clinical use as an anti-depressant[376].…”

Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

“…Despite the accumulated knowledge and previous clinical trials in different fields, including the cardiovascular system, the only marketed drug in the United States containing a ROCK inhibitor, named netarsudil, is an ophthalmic solution indicated for glaucoma [191]. Ripasudil has similar uses in Japan [192]. Fasudil, one of the ROCK inhibitors used in several studies included in this review, has also been used in Japan as an injectable formulation to reduce cerebral vasospasm following subarachnoid hemorrhage [193] but is still unapproved by other governmental regulatory healthy agencies.…”