1.
Netarsudil Improves Trabecular Outflow Facility in Patients with Primary Open Angle Glaucoma or Ocular Hypertension: A Phase 2 Study.
Sit, AJ, Gupta, D, Kazemi, A, McKee, H, Challa, P, Liu, KC, Lopez, J, Kopczynski, C, Heah, T
American journal of ophthalmology. 2021;:262-269
Abstract
PURPOSE Intraocular pressure (IOP) reduction is key to controlling primary open angle glaucoma (POAG). Pharmacotherapies for POAG or ocular hypertension (OHT) commonly lower IOP by increasing uveoscleral outflow or decreasing aqueous humor production. Netarsudil (Rhopressa), a Rho kinase inhibitor, reduces IOP by improving trabecular outflow facility, which is reduced in POAG. We investigated the effects of netarsudil on aqueous humor dynamics in patients with POAG or OHT. DESIGN Double-masked, randomized, vehicle-controlled, Phase 2 trial. METHODS Netarsudil 0.02% was instilled in 1 eye and vehicle into the contralateral eye of 20 patients once daily in the morning for 7 days. The primary endpoint was change in mean diurnal outflow facility on day 8 versus that on day 1 (baseline). Outflow facility was measured by using Schiøtz tonography, IOP by pneumotonometry, and episcleral venous pressure (EVP) by automated venomanometry. RESULTS Eighteen patients (90%) completed the study. Mean diurnal outflow facility increased 0.039 versus 0.007 µL/min/mm Hg from baseline in the netarsudil- and the vehicle-treated groups, respectively (P < .001 vs. baseline for netarsudil), a treatment difference of 0.03 µL/min/mm Hg (P ≤ .001). Mean diurnal IOP change from baseline at day 8 was -4.52 mm Hg for netarsudil versus -0.98 mm Hg for vehicle, a treatment difference of -3.54 mm Hg (P < .0001). Mean diurnal EVP change from baseline was -0.79 mm Hg in the netarsudil-treated group versus 0.10 mm Hg for vehicle, a treatment difference of -0.89 mm Hg (P < .001). All patients reporting an adverse event reported conjunctival hyperemia of mild or moderate severity. CONCLUSIONS Netarsudil acts on the conventional outflow pathway, both proximal and distal, to significantly reduce IOP in POAG and OHT by improving trabecular outflow facility and decreasing EVP.
2.
Randomized, Double-Masked Trial of Netarsudil 0.02% Ophthalmic Solution for Prevention of Corticosteroid-Induced Ocular Hypertension.
Price, MO, Feng, MT, Price, FW
American journal of ophthalmology. 2021;:382-387
Abstract
PURPOSE To assess whether prophylactic use of netarsudil 0.02% ophthalmic solution reduces the risk of intraocular pressure (IOP) elevation associated with prolonged use of topical corticosteroids to prevent cornea transplantation rejection. DESIGN Prospective, randomized clinical trial. METHODS In this study, 120 subjects were randomized to use netarsudil (off-label) or placebo once daily for 9 months after Descemet membrane endothelial keratoplasty, and 71 fellow eyes were enrolled and assigned to the opposite treatment arm. Participants concurrently used topical prednisolone acetate 1% 4× daily for 3 months, 3× daily for a month, twice daily for a month, and once daily for 4 months. The main outcome was IOP elevation (defined as IOP ≥24 mm Hg or an increase of ≥10 mm Hg over baseline) assessed by Kaplan-Meier and proportional hazards analyses, taking loss to follow-up into consideration. RESULTS Overall, 95 eyes were assigned to netarsudil and 96 to placebo; 15 eyes (16%) were withdrawn early from the netarsudil arm because of ocular irritation. The rate of IOP elevation was 14% with netarsudil and 21% with placebo (relative risk: 0.6; 95% confidence interval: 0.3-1.3; P = .23). IOP was >30 mm Hg in 7.8% assigned to netarsudil versus 7.4% assigned to placebo (P = .84). Median 6-month central endothelial cell loss was 31% versus 29% with netarsudil versus placebo, respectively (P = .49). CONCLUSIONS Netarsudil did not produce a statistically significant reduction in the risk of steroid-induced IOP elevation after corneal transplantation relative to placebo.
3.
Tamibarotene maintenance improved relapse-free survival of acute promyelocytic leukemia: a final result of prospective, randomized, JALSG-APL204 study.
Takeshita, A, Asou, N, Atsuta, Y, Sakura, T, Ueda, Y, Sawa, M, Dobashi, N, Taniguchi, Y, Suzuki, R, Nakagawa, M, et al
Leukemia. 2019;(2):358-370
Abstract
Between April 2004 and December 2010, we conducted a prospective randomized controlled study comparing tamibarotene with all-trans retinoic acid (ATRA) in the maintenance therapy of newly diagnosed acute promyelocytic leukemia (APL), and here report the final results of this study with a median follow-up of 7.3 years. Of 344 eligible patients who had received ATRA and chemotherapy, 319 (93%) achieved complete remission (CR). After completion of three courses of consolidation chemotherapy, 269 patients in molecular remission underwent maintenance randomization, 135 to ATRA (45 mg/m2 daily), and 134 to tamibarotene (6 mg/m2 daily) for 14 days every 3 months for 2 years. The primary endpoint was relapse-free survival (RFS). The 7-year RFS was 84% in the ATRA arm and 93% in the tamibarotene arm (p = 0.027, HR = 0.44, 95% CI, 0.21 to 0.93). The difference was prominent in high-risk patients with initial leukocytes ≥ 10.0 × 109/L (62% vs. 89%; p = 0.034). Tamibarotene was significantly superior to ATRA by decreasing relapse in high-risk patients. Overall survival after randomization did not differ (96% vs. 97%; p = 0.520). Secondary hematopoietic disorders developed in nine patients, secondary malignancies in 11, and grade 3 or more late cardiac comorbidities in three. These late complications did not differ between the two arms.