Transcript ACUVAIL™: Corneal Wound Healing Model

Fixed-Combination Brimonidine-Timolol vs
Latanoprost in Glaucoma and Ocular
Hypertension Patients: A 12-Week,
Randomized, Comparison Study
L. Jay Katz, MD1; Steven H. Rauchman, MD2; Andrew J. Cottingham, MD3;
Steven T. Simmons, MD4; Julia Williams, MA5; Rhett M. Schiffman, MD5;
David A. Hollander, MD, MBA5
1Wills
Eye Hospital, Philadelphia, PA; 2North Valley Eye Medical Group, Mission Hills, CA;
3South Texas Eye Institute, San Antonio, TX; 4Glaucoma Consultants of the Capital Region,
Slingerlands, NY; 5Allergan, Inc., Irvine, CA
Study funded by Allergan, Inc.
Dr. L. Jay Katz received research support and travel reimbursement from Allergan, Inc. Drs. Steven H.
Rauchman , Andrew J. Cottingham, and Steven T. Simmons received research support from Allergan, Inc.
Ms. Julia Williams, Dr. Rhett M. Schiffman, and Dr. David A. Hollander are employees of Allergan, Inc.
Introduction
•
Reducing intraocular pressure (IOP) to a low target pressure minimizes the risk of
progression in glaucoma.1
•
Prostaglandin analogs (PGAs), including latanoprost, bimatoprost, and travoprost, are
commonly used as first-line therapy in glaucoma and ocular hypertension (OHT).
•
Treatment decisions must be individualized. While IOP lowering is ideally controlled with
monotherapy, over 20% of PGA patients, for example, may be required to add another
IOP-lowering medication to their treatment regimen within a year of initiating treatment.2
•
The fixed combination of brimonidine 0.2% and the beta-blocker timolol 0.5%
(Combigan®; Allergan, Inc.) acts by a dual mechanism of action: increasing uveoscleral
outflow and decreasing aqueous production.3
•
Fixed-combination brimonidine-timolol has been shown to be well tolerated and to
reduce IOP more effectively than either brimonidine or timolol used as monotherapy.4
•
The purpose of this study was to evaluate the IOP-lowering efficacy of fixed-combination
brimonidine-timolol compared with latanoprost in patients with glaucoma or OHT.
Methods
•
This was a prospective, randomized, multicenter, investigator-masked, parallel-group study.
•
Eligible patients were adults at least 18 years of age with a diagnosis of glaucoma or OHT
requiring treatment with IOP-lowering medication.
•
Any IOP-lowering medication used previously was washed out prior to the baseline visit.

Washout periods ranged from 4 days for parasympathomimetics and carbonic anhydrase inhibitors to
4 weeks for beta-blockers and PGAs.
•
At the baseline visit, patients with IOP ≥ 24 mm Hg and < 34 mm Hg in at least 1 eye at 8 AM
were randomized to treatment with twice-daily fixed brimonidine-timolol (n = 73) or once-daily
latanoprost (n = 75, dosed in the evening with a vehicle control in the morning to maintain
masking) for 12 weeks.
•
IOP was measured at 8 AM (immediately prior to dosing), 10 AM, and 3 PM at baseline, week 6,
and week 12.
•
The primary efficacy endpoint was the mean diurnal IOP at week 12.
•
Safety measures included biomicroscopy, with findings graded on a scale of 0 = none,
+0.5 = trace, +1 = mild, +2 = moderate, and +3 = severe.
•
Efficacy was evaluated in the worse eye (the eye with higher mean diurnal IOP at baseline)
based on the intent-to-treat population of all randomized patients with last observation carried
forward for missing values.
•
Mean diurnal IOP was compared between treatment groups with 2-sample t-tests; proportions of
patients were compared between treatment groups with Fisher exact tests.
Patient Demographics
Fixed Brimonidine-Timolol
(n = 73)
Latanoprost
(n = 75)
Mean (SD) age, years
63.3 (12.7)
63.6 (12.0)
Female, n (%)
42 (57.5%)
44 (58.7%)
5 (6.8%)
6 (8.0%)
Caucasian
48 (65.8%)
48 (64.0%)
Hispanic
17 (23.3%)
17 (22.7%)
Asian
1 (1.4%)
2 (2.7%)
Other
2 (2.7%)
2 (2.7%)
Race/ethnicity, n (%)
Black
•
Most of the patients enrolled in the study were Caucasian and female.
Results: Mean Diurnal IOP
30
P = .118
Mean IOP (mm Hg)
25
24.7
Fixed Brimonidine-Timolol (n = 73)
Latanoprost (n = 75)
25.4
P = .794
20
17.8
15
17.9
10
Error bars, SEM.
5
0
Baseline
Week 12
Study Visit
•
There was no statistically significant difference between treatment groups in mean
diurnal IOP at baseline or week 12 (primary study endpoint).
•
The mean percent reduction in diurnal IOP from baseline at week 12 was 28% in
the fixed brimonidine-timolol group and 30% in the latanoprost group (P = .347).
Results: Percentage of Patients Achieving a ≥ 20%
Reduction From Baseline Mean Diurnal IOP at Week 12
Percentage of Patients
100
80
P = .131 vs latanoprost.
87.7%
77.3%
60
40
20
0
Fixed
Brimonidine-Timolol
(n = 73)
Latanoprost
(n = 75)
•
There was no statistically significant difference between treatment groups in
responder rates.
•
At Week 12, 87.7% of patients treated with fixed brimonidine-timolol and 77.3% of
patients treated with latanoprost achieved at least a 20% reduction in mean diurnal
IOP from baseline (P = .131).
Results: Percentage of Patients Achieving a Mean
Diurnal IOP of < 18 mm Hg at Week 12
Percentage of Patients
100
80
P = .325 vs latanoprost.
60
60.3%
52.0%
40
20
0
Fixed
Brimonidine-Timolol
(n = 73)
Latanoprost
(n = 75)
•
There was no statistically significant difference between treatment groups in the
achievement of diurnal IOP < 18 mm Hg.
•
At Week 12, 60.3% of patients treated with fixed brimonidine-timolol and 52.0% of
patients treated with latanoprost achieved a mean diurnal IOP of < 18 mm Hg
(P = .325).
Mean Scores on Biomicroscopy
Erythema (Lids/Lashes)
3
Fixed Brimonidine-Timolol (n = 73)
Latanoprost (n = 75)
Mean Score
Mean Score
3
Hyperemia (Conjunctiva)
2
1
Latanoprost (n = 75)
2
1
0
0
Baseline
Week 6
Week 12
Baseline
Follicles (Conjunctiva)
3
Fixed Brimonidine-Timolol (n = 73)
Latanoprost (n = 75)
2
1
Week 12
Fixed Brimonidine-Timolol (n = 73)
Latanoprost (n = 75)
2
1
0
0
Baseline
Week 6
Corneal Staining
Mean Score
Mean Score
3
•
Fixed Brimonidine-Timolol (n = 73)
Week 6
Week 12
Baseline
Week 6
Week 12
Mean scores on all biomicroscopic parameters remained in the none (0) to trace (+0.5) range in both
treatment groups.
Discussion
•
Primary considerations in choosing antiglaucoma medication for use in individual
patients include IOP-lowering efficacy and tolerability.
•
In this study, fixed brimonidine-timolol and latanoprost demonstrated similar efficacy in
lowering IOP in patients with glaucoma or OHT.

Fixed brimonidine-timolol and latanoprost provided equivalent mean diurnal IOP after 12 weeks
of treatment.

Patients treated with fixed brimonidine-timolol were at least as likely as patients treated with
latanoprost to achieve a mean diurnal IOP < 18 mm Hg and 20% or larger reductions in mean
diurnal IOP from baseline at week 12.
•
Biomicroscopic examinations showed a favorable ocular surface tolerability profile of
both fixed brimonidine-timolol and latanoprost.
•
These results suggest that fixed brimonidine-timolol may be an acceptable alternative to
latanoprost for treatment of patients with glaucoma or OHT.
•
Currently, the primary aim of glaucoma treatment is to reduce IOP to a low target
pressure. In the future, treatment strategies also may strive to improve the health and
viability of retinal ganglion cells.

At the present time, preclinical studies have suggested that brimonidine can reduce retinal ganglion cell loss
and vision loss independently of IOP.5 Further investigations are required to replicate these in vitro findings in a
clinical setting.
Conclusions
• Fixed-combination brimonidine-timolol was as effective as
latanoprost in reducing IOP in patients with glaucoma or OHT.
• Both treatments demonstrated favorable ocular surface
tolerability.
References
1. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship
between control of intraocular pressure and visual field deterioration. Am J Ophthalmol.
2000;130(4):429-440.
2. Covert D, Robin AL. Adjunctive glaucoma therapy use associated with travoprost, bimatoprost, and
latanoprost. Curr Med Res Opin. 2006;22(5):971-976.
3. Cantor LB. Brimonidine in the treatment of glaucoma and ocular hypertension. Ther Clin Risk
Manag. 2006;2(4):337-346.
4. Sherwood MB, Craven ER, Chou C, et al. Twice-daily 0.2% brimonidine-0.5% timolol fixedcombination therapy vs monotherapy with timolol or brimonidine in patients with glaucoma or ocular
hypertension: a 12-month randomized trial. Arch Ophthalmol. 2006;124(9):1230-1238.
5. Gandolfi SA, Sangermani C, Cimino L, et al. Is there a non IOP-related effect of brimonidine on
visual field progression in human glaucoma? Invest Ophthalmol Vis Sci. 2004;45:E-Abstract 2298.
Author Bio and Photo
L. Jay Katz, MD, FACS, is a Professor
of Ophthalmology at Jefferson Medical
College and Director of the Glaucoma
Service at Wills Eye Institute,
Philadelphia. He received his MD
degree from Yale University Medical
School and completed an internship in
Internal Medicine at the University of
Virginia, a residency in Ophthalmology
at Yale, and a Fellowship in Glaucoma
at Wills Eye Hospital. He received the
2002 AAO Senior Achievement Award.
His research interests include glaucoma.