TY - JOUR

T1 - Phase 3, Randomized, 20-Month Study of Bimatoprost Implant in Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 1)

AU - Medeiros, Felipe A.

AU - Walters, Thomas R.

AU - Kolko, Miriam

AU - Coote, Michael

AU - Bejanian, Marina

AU - Goodkin, Margot L.

AU - Guo, Qiang

AU - Zhang, Jane

AU - Robinson, Michael R.

AU - Weinreb, Robert N.

AU - ARTEMIS 1 Study Group

AU - Agar, Ashish

AU - Coote, Michael

AU - Bathijia, Renuka

AU - Bach-Holm, Daniella

AU - Walters, Thomas R.

AU - Zaman, Fiaz

AU - Zhang, Rui

PY - 2020

Y1 - 2020

N2 - Purpose: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations. Design: Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. Participants: Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 AM) of 22–32 mmHg after washout. Methods: Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit. Main Outcome Measures: Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results: Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5–17.2, 16.5–17.0, and 17.1–17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit. Conclusions: Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.

AB - Purpose: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations. Design: Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. Participants: Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 AM) of 22–32 mmHg after washout. Methods: Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit. Main Outcome Measures: Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results: Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5–17.2, 16.5–17.0, and 17.1–17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit. Conclusions: Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.

U2 - 10.1016/j.ophtha.2020.06.018

DO - 10.1016/j.ophtha.2020.06.018

M3 - Journal article

C2 - 32544560

AN - SCOPUS:85089012127

VL - 127

SP - 1627

EP - 1641

JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

IS - 12

ER -