ARTEMIS 1: Bimatoprost implant noninferior to timolol in lowering IOP
Bimatoprost implant of either 10- or 15-μg dose strength is noninferior to timolol through week 12 in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT), according to the results of the phase III trial ARTEMIS 1.
“One year after three administrations [of bimatoprost], intraocular pressure (IOP) was controlled in most [patients] without additional treatment,” the researchers said. “The risk-benefit assessment favoured the 10-μg implant over the 15-μg implant.”
ARTEMIS 1 is a 20-month, randomized, multicentre, blinded, parallel-group, phase III clinical study, which enrolled adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP of 22–32 mm Hg after washout. On day 1, study eyes received bimatoprost implant 10 (n=198) or 15 μg (n=198) with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n=198). IOP was measured at hours 0 and 2 at each visit.
Both dose strengths of bimatoprost implant met the primary endpoint of noninferiority to timolol after each administration. Mean diurnal IOP at baseline was 24.0 mm Hg in the 10-μg implant group, 24.2 mm Hg in the 15-μg implant group, and 23.9 mm Hg in the timolol group. At week 12, mean diurnal IOP dropped from 16.5–17.2, 16.5–17.0, and 17.1–17.5 mm Hg in the 10-μg implant, 15-μg implant, and timolol groups. [Ophthalmology 2020;127:1627-1641]
However, the incidence of corneal and inflammatory treatment-emergent adverse events (TEAEs), such as corneal endothelial cell density (CECD) loss and iritis, was higher in the bimatoprost implant group than the timolol group and highest in those who received the 15-μg dose strength.
Corneal TEAE incidence increased following repeated treatment. Three administrations at fixed 16-week intervals resulted in ≥20-percent CECD loss in 10.2 percent and 21.8 percent of eyes in the 10- and 15-μg implant groups, respectively. Moreover, mean best-corrected visual acuity (BCVA) was stable. Three implant-treated patients with corneal TEAEs had >2-line BCVA loss at their last visit.
These findings are consistent with those of a small 2-year phase I/II study, wherein no iris pigmentation, eyelash growth, or periorbital fat atrophy was reported in eyes treated with bimatoprost implant despite the occurrence of these AEs in fellow eyes treated with topical bimatoprost. [Drugs 2020;80:167-179]
Of note, the extended duration of effect of bimatoprost implant on IOP appears to be driven by durable matrix metalloproteinase (MMP)-mediated remodeling of aqueous humor outflow pathways. [Drugs 2020;80:167-179; J Ocul Pharmacol Ther 2019;35:138-144]
“The mechanism of IOP lowering by prostaglandin analogues is believed to involve concentration-dependent upregulation of MMP expression and activity in the ciliary body and trabecular meshwork, resulting in increased extracellular matrix turnover and decreased resistance to aqueous outflow through unconventional and conventional pathways,” the researchers said. [Invest Ophthalmol Vis Sci 2001;42:1514-1521; Invest Ophthalmol Vis Sci 2002;43:716-722; BMC Ophthalmol 2016;16:26]
“Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss,” they added.