Effectiveness of Netarsudil versus Brimonidine in Eyes already Being Treated with Glaucoma Medications at a Single Academic Tertiary Care Practice: A Comparative Study

Rho kinase inhibitors, such as netarsudil, are a relatively new class of medications recently introduced into the market for the treatment of glaucoma, the leading cause of irreversible blindness in the world. Previous clinical trials have studied netarsudil's efficacy when used as a first- or second-line agent but limited studies have investigated its effectiveness in the real world where it is more commonly used as a third, fourth, or fifth agent in combination with other topical medications. Equally important, prior studies have not compared its effectiveness to its peer medications in these settings. To compare intraocular pressure (IOP) lowering after initiation of netarsudil or brimonidine therapy in patients with glaucoma using >2 medications for IOP management. A chart review of 369 eyes from 279 patients followed at a single academic tertiary practice was performed with an institutional review board waiver of consent to compare IOP lowering after prescription of netarsudil (n = 176) versus brimonidine (n = 193) as a third, fourth, or fifth IOP-lowering agent. Patients were identified by querying the electronic medical record for those with a glaucoma-related diagnosis who were prescribed either medication. Five sequential IOP measurements were obtained to determine the mean change in IOP before and after treatment (ΔIOP = mean IOP4,5 – mean IOP1,2,3). A multilevel linear mixed-effects model assessed the influence of medication (independent variable) on ΔIOP (dependent variable). Additional independent variables of interest included the number of glaucoma medications at baseline, age, sex, glaucoma type and severity, race, and pretreatment IOP. Bootstrap analysis was performed to remove sampling bias and confirm mixed-effects model findings. Kaplan-Meier survival analysis evaluated the probability of requiring additional intervention within 3 years following the date of medication prescription. The unadjusted mean (SD) ΔIOP for netarsudil and brimonidine was −2.20 (4.11) mm Hg and −2.21 (3.25) mm Hg, respectively (P = 0.484). The adjusted linear mixed-effects models and bootstrap analysis demonstrated that there was no statistical difference in IOP-lowering effectiveness between the medications. Netarsudil and brimonidine failed to adequately control IOP at similar rates with 42% and 47% probabilities of survival respectively by the 3-year follow-up (P = 0.520). When escalating pharmacologic therapy, the IOP-lowering effect of netarsudil appeared t