A multicenter, open-label study of netarsudil for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension in a real-world setting

Figures & data

Table 1. Patient disposition.

n (%)	Overall population	Netarsudil monotherapy	Netarsudil with concomitant therapy
Enrolled	261
Safety population	260	99	161
mITT population	242	91	151
Per protocol population^a	217	80	137
Treated patients	260	99	161
Completed study	219 (84.2)	81 (81.8)	138 (85.7)
Discontinued study	41 (15.8)	18 (18.2)	23 (14.3)
Treatment-emergent AE	29 (11.2)	12 (12.1)	17 (10.6)
Non–treatment-emergent AE^b	1 (0.4)	1 (1.0)	0 (0.0)
Lost to follow up	2 (0.8)	0 (0.0)	2 (1.2)
Other	9 (3.5)	5 (5.1)	4 (2.5)

Abbreviations. AE, adverse event; mITT, modified intent to treat.

^aPatients in the mITT population who completed 12 weeks of study treatment without significant protocol violations. Two patients who completed the study had protocol deviations considered major and were excluded from the per protocol population; neither patient was taking study medication at the time of the week 6 visit.

^bOne patient discontinued early due to a non–treatment-emergent AE. Onset of the AE occurred after the patient had stopped netarsudil.

Table 2. Baseline demographic and clinical characteristics (mITT population).

	Overall, N = 242	Netarsudil monotherapy, n = 91	Netarsudil with concomitant therapy, n = 151
Age, years
Mean (SD)	67.2 (11.02)	67.2 (11.85)	67.2 (10.53)
Median	69.0	69.0	69.0
Min–max	21–90	21‒88	30‒90
Gender, n (%)
Female	148 (61.2)	57 (62.6)	91 (60.3)
Male	94 (38.8)	34 (37.4)	60 (39.7)
Ethnicity, n (%)
Hispanic or Latino	19 (7.9)	11 (12.1)	8 (5.3)
Not Hispanic or Latino	223 (92.1)	80 (87.9)	143 (94.7)
Race, n (%)
American Indian or Alaska Native	1 (0.4)	1 (1.1)	0 (0.0)
Asian	3 (1.2)	0 (0.0)	3 (2.0)
Black or African American	58 (24.0)	13 (14.3)	45 (29.8)
Native Hawaiian or Other Pacific Islander	0 (0.0)	0 (0.0)	0 (0.0)
White	179 (74.0)	77 (84.6)	102 (67.5)
Other^a	1 (0.4)	0 (0.0)	1 (0.7)
Systolic blood pressure, mmHg
Mean (SD)	133.6 (16.05)	131.1 (13.11)	135.1 (17.45)
Median	132.0	131.0	132.0
Min–max	90‒206	90‒175	101‒206
Diastolic blood pressure, mmHg
Mean (SD)	79.7 (9.77)	78.3 (7.95)	80.6 (10.65)
Median	79.0	79.0	79.0
Min–max	58‒118	59‒106	58‒118
Iris colour, n (%)
Black	1 (0.4)	0 (0.0)	1 (0.7)
Blue	64 (26.4)	29 (31.9)	35 (23.2)
Brown	132 (54.5)	46 (50.5)	86 (57.0)
Green	11 (4.5)	2 (2.2)	9 (6.0)
Grey	2 (0.8)	1 (1.1)	1 (0.7)
Hazel	32 (13.2)	13 (14.3)	19 (12.6)
Central corneal thickness, µm
Mean (SD)	557.8 (45.37)	566.1 (41.77)	552.9 (46.85)
Median	561.0	569.0	553.0
Min–max	427‒737	464‒689	427‒737

^aAmerican Indian or Alaska Native/White.

Table 3. Ophthalmic medical history (mITT population).

	Overall, N = 242	Netarsudil monotherapy, n = 91	Netarsudil with concomitant therapy, n = 151
Glaucoma diagnosis, n (%)
Ocular hypertension	37 (15.3)	18 (19.8)	19 (12.6)
Open-angle glaucoma	191 (78.9)	72 (79.1)	119 (78.8)
Closed-angle glaucoma with patent iridotomy	2 (0.8)	0 (0.0)	2 (1.3)
Pseudoexfoliative glaucoma	2 (0.8)	0 (0.0)	2 (1.3)
Pigmentary glaucoma	4 (1.7)	1 (1.1)	3 (2.0)
Other^a	6 (2.5)	0 (0.0)	6 (4.0)
Years with elevated IOP, n (%)
Newly diagnosed	25 (10.3)	15 (16.5)	10 (6.6)
1–3 years	32 (13.2)	10 (11.0)	22 (14.6)
4–5 years	28 (11.6)	10 (11.0)	18 (11.9)
6–10 years	50 (20.7)	16 (17.6)	34 (22.5)
11–20 years	78 (32.2)	30 (33.0)	48 (31.8)
>20 years	29 (12.0)	10 (11.0)	19 (12.6)
Historical untreated IOP, mmHg
N	208	83	125
Mean (SD)	25.9 (5.67)	24.4 (4.26)	26.9 (6.25)
Median	25.0	24.0	27.0
Min–max	14–48	14–36	14–48
Historical maximum treated IOP, mmHg
N	229	81	148
Mean (SD)	22.9 (5.94)	21.8 (4.52)	23.5 (6.52)
Median	22.0	22.0	23.0
Min–max	8–50	15–36	8–50
Previous procedures – study eye, n (%)^b
None	96 (39.7)	44 (48.4)	52 (34.4)
Glaucoma laser (ALT/SLT/iridotomy)	90 (37.2)	26 (28.6)	64 (42.4)
Cataract surgery	87 (36.0)	31 (34.1)	56 (37.1)
MIGS	12 (5.0)	2 (2.2)	10 (6.6)
Retinal surgery	10 (4.1)	4 (4.4)	6 (4.0)
Refractive surgery	8 (3.3)	2 (2.2)	6 (4.0)
Trabeculectomy or valve	8 (3.3)	0 (0.0)	8 (5.3)
Oculoplastic surgery	7 (2.9)	4 (4.4)	3 (2.0)
Corneal surgery	1 (0.4)	0 (0.0)	1 (0.7)

Abbreviations. ALT, argon laser trabeculoplasty; IOP, intraocular pressure; MIGS, minimally invasive glaucoma surgery; SLT, selective laser trabeculoplasty.

^aOther includes 1 subject with glaucoma suspect, 1 subject with low-tension glaucoma, and 4 subjects with normal-tension glaucoma.

^bPatients may have had more than 1 previous ocular procedure.

Figure 1. Percentages of netarsudil monotherapy patients who achieved intraocular pressure thresholds in the study eye at week 12 (mITT population). (A) All netarsudil monotherapy patients; (B) netarsudil monotherapy replaced prostaglandin analog therapy; (C) treatment-naïve netarsudil monotherapy patients.

Figure 2. Percentages of patients receiving concomitant therapy who achieved intraocular pressure thresholds in the study eye at week 12 (mITT population). (A) all concomitant therapy patients; (B) netarsudil added to a prostaglandin analog; (C) netarsudil added to multiple drug classes; (D) netarsudil replaced 1 drug class or multiple drug classes (i.e. 2-agent fixed dose combinations) as concomitant therapy.

Table 4. Intraocular pressure of the study eye in patients receiving concomitant therapy (mITT population).

	Netarsudil added to monotherapy (added to PGA or BB)	Netarsudil added to concomitant therapy (added to ≥ 2 classes concomitant therapy)	Netarsudil replaced ≥1 class in concomitant therapy
Baseline
n	57	64	30
Mean (SD), mmHg	21.2 (4.49)	20.6 (5.81)	18.2 (2.96)
Min–max, mmHg	10.0–35.0	12.0–49.0	13.0–23.0
Week 6
n	57	64	30
Mean (SD), mmHg	17.1 (4.25)	16.9 (5.16)	16.8 (3.89)
Mean change (SD), mmHg	−4.0 (2.82)	−3.7 (2.92)	−1.4 (3.34)
Mean % change (SD), mmHg	−18.8 (12.72)	−17.5 (15.43)	−7.0 (18.24)
Week 12
n	54	61	28
Mean (SD), mmHg	16.9 (4.45)	16.2 (5.86)	17.8 (3.39)
Mean change (SD), mmHg	−4.3 (2.88)	−4.5 (4.08)	−0.4 (2.47)
Mean % change (SD), mmHg	−20.5 (12.94)	−20.9 (17.62)	−1.7 (12.90)

Netarsudil added to concomitant therapy group includes fixed-dose combination (brinzolamide/brimonidine, dorzolamide/timolol, brimonidine/timolol, brimonidine/dorzolamide/timolol) and/or PGA (bimatoprost, travoprost, latanoprost, latanoprostene bunod, tafluprost) and/or alpha agonist (brimonidine) and/or BB (timolol, levobunolol, betaxolol) and/or carbonic anhydrase inhibitor (methazolamide, dorzolamide, brinzolamide). Abbreviations. BB, beta blocker; PGA, prostaglandin analog.

Table 5. Summary of adverse events.

n (%)	Overall, N = 260	Netarsudil monotherapy, n = 99	Netarsudil with concomitant therapy, n = 161
Patients with ≥1 AE	105 (40.4)	37 (37.4)	68 (42.2)
Patients with ≥1 ocular AE	90 (34.6)	34 (34.3)	56 (34.8)
Patients with ≥1 treatment-related AE^a	83 (31.9)	29 (29.3)	54 (33.5)
Patients with ≥1 ocular treatment-related AE	82 (31.5)	28 (28.3)	54 (33.5)
Patients with AEs leading to discontinuation^b	29 (11.2)	12 (12.1)	17 (10.6)
Patients with ocular-related AEs leading to discontinuation^b	26 (10.0)	9 (9.1)	17 (10.6)
Serious AEs	3	2	1
Ocular serious AEs	1	1	0
Treatment-related serious AEs	0	0	0
Deaths	0	0	0
AEs reported by ≥5% of patients
Conjunctival hyperemia	54 (20.8)	22 (22.2)	32 (19.9)
Vision blurred	19 (7.3)	9 (9.1)	10 (6.2)
Conjunctival hemorrhage	14 (5.4)	6 (6.1)	8 (5.0)
Instillation site pain	14 (5.4)	6 (6.1)	8 (5.0)

Abbreviation. AE, adverse event.

^aEach adverse event was evaluated by the investigator as not related, unlikely related, possibly related, or related to treatment. The patients shown here experienced adverse events assessed as unlikely related, possibly related, or related to treatment.

^bOne patient was excluded from this table because of early discontinuation due to a non–treatment-emergent event.