Transcript Mean Diurnal IOP

The Effect of Bimatoprost 0.03% vs
Travoprost 0.004% in Patients on
Latanoprost 0.005% Requiring
Additional IOP Lowering
Jeffrey A. Kammer,1 Barry Katzman,2 Stacey L. Ackerman,3
and David Hollander4
1. Vanderbilt Eye Institute, Nashville, TN; 2. West Coast Eye Care Associates,
San Diego, CA; 3. Philadelphia Eye Associates, Philadelphia, PA;
4. Allergan, Inc., Irvine, CA
Financial Disclosure
This study was sponsored by Allergan, Inc.
J.A. Kammer, B. Katzman, and S.L. Ackerman have no proprietary interest
in any of the prostaglandin analogs or their manufacturers.
D. Hollander is an employee of Allergan, Inc.
Abstract
 Purpose: To evaluate the efficacy/safety of switching latanoprost patients requiring
additional intraocular pressure (IOP) lowering to either bimatoprost or travoprost.
 Methods: Investigator-masked, prospective, multicentered study (17 sites) of patients
on latanoprost requiring additional IOP lowering randomized to bimatoprost or
travoprost.
 Results: A total of 266 patients on latanoprost were randomized to bimatoprost or
travoprost. On latanoprost therapy, the 2 groups had equivalent mean diurnal baseline
IOPs (19.1 mm Hg, 18.9 mm Hg; P = .473). At 3 months, the additional mean diurnal
reduction from baseline was 2.1 mm Hg for bimatoprost and 1.4 mm Hg for travoprost
(P = .024). In patients with baseline IOP < 20 mm Hg (n = 145) on latanoprost,
additional IOP lowering for bimatoprost was 1.8 mm Hg vs 0.5 mm Hg for travoprost
(P < .001). Physician-documented hyperemia rates (11% for bimatoprost and 17% for
travoprost) and corneal staining (4% for bimatoprost and 5% for travoprost) were not
statistically different.
 Conclusion: At 3 months, bimatoprost provided greater mean diurnal IOP lowering
than travoprost in patients on latanoprost who required additional IOP lowering.
Additional IOP lowering was observed with bimatoprost, even at relatively low
latanoprost baselines. Longer follow-up is needed to further evaluate the effects of
switching prostaglandin analogs (PGAs).
Introduction
 A primary goal of medical therapy in glaucoma is to reduce intraocular pressure
(IOP). Monotherapy with a single IOP-lowering medication is preferred to improve
compliance and minimize the adverse effects and other costs of treatment. Patients
who fail to achieve their target pressure on a particular medication may be able to
maintain monotherapy if they are successfully switched to another more effective
monotherapy.
 Data from randomized clinical trials suggest that among the prostaglandin analogs
(PGAs), bimatoprost and possibly travoprost may reduce IOP more effectively than
latanoprost.1-3
 Studies have shown that patients uncontrolled on or unresponsive to latanoprost may
have substantial additional IOP lowering when they are switched to bimatoprost or
travoprost therapy.4-6 Increased efficacy has also been observed on a population level
when patients were systematically switched from latanoprost to bimatoprost.7
 The purpose of the present study was to evaluate the efficacy and tolerability of
switching patients from latanoprost monotherapy to either bimatoprost or travoprost
monotherapy when IOP was not sufficiently reduced by latanoprost alone.
References: 1. Netland et al. Am J Ophthalmol. 2001;132:472-484; 2. Simmons et al. Adv Ther. 2004;21:247-262; 3. Maul et al. Clin Ther. 2007;29:1915-1923;
4. Gandolfi and Cimino. Ophthalmology. 2003;110:609-614; 5. Williams. Adv Ther. 2002;19:275-281; 6. Hollo et al. Curr Med Res Opin. 2005;21:1943-1948;
7. Law et al. Ophthalmology. 2005;112:2123-2130.
Methods: Study Design and Patients
 This was a randomized, prospective, multicenter (17 sites), investigator-masked,
parallel-group clinical study.
 Adult patients diagnosed with glaucoma or ocular hypertension in each eye who had
inadequate IOP control after at least 30 days on bilateral latanoprost monotherapy
were enrolled.
–
Inadequate IOP control was determined by failure of the patient to achieve the target pressure set
by the investigator.
 Primary exclusion criteria included previous inadequate IOP response to bimatoprost
or travoprost and known hypersensitivity or contraindication to any component of the
study medications.
 Patient eligibility was determined at a screening visit following at least 30 days on
latanoprost monotherapy, and patients were subsequently run-in for an additional 2
weeks on latanoprost monotherapy before a baseline visit.
 Study visits were scheduled at baseline (following 2-week latanoprost run-in), month 1,
and month 3.
 At baseline, patients discontinued latanoprost therapy and were randomized to
1 of 2 treatment groups:
–
Bimatoprost 0.03% (Lumigan®; Allergan, Inc.; Irvine, CA)
–
Travoprost 0.004% (Travatan®; Alcon Laboratories Inc.; Fort Worth, TX)
 Study drugs were administered once daily in the evening for 3 months.
Methods: Outcome Measures and
Analysis
 IOP was measured at 9 AM and 4 PM (± 1 hour) at each study visit.
 The primary efficacy outcome measures were mean diurnal IOP and mean IOP at each
timepoint.
– Diurnal IOP for a patient was defined as the mean of the 9 AM and 4 PM measurements taken at a
particular visit.
 Safety outcome measures included ocular signs (biomicroscopy) and symptoms.
 All adverse events were recorded, and their severity and potential relationship to study
treatment were documented.
– An adverse event was defined as any new condition, worsening of a preexisting condition, or
recurrence of a condition that had resolved after the baseline visit.
 Biomicroscopic findings were graded on a 4-grade scale of none-to-trace (0 to 0.5),
mild (1), moderate (2), and severe (3).
 Analyses of IOP were based on the worse eye (the eye with the higher IOP at 9 AM on
baseline) for the intent-to-treat patient population with no imputation for missing values.
 Baseline differences in IOP between treatment groups were evaluated using analysis of
variance (ANOVA).
 An analysis of covariance (ANCOVA) model with baseline IOP as the covariate was
used to evaluate differences between treatment groups at follow-up.
Results: Patient Characteristics and
Disposition
Bimatoprost (n = 131)
Travoprost (n = 135)
Mean age (years)
63.4
62.7
Sex (male/female)
38%/62%
51%/49%
Black
28%
24%
White
57%
59%
Hispanic or Latino
12%
11%
3%
5%
63%/37%
62%/38%
Ocular hypertension
21%
22%
Chronic open-angle glaucoma
77%
73%
2%
5%
Race
Other
Eye color (dark/light)
Diagnosis
Other
 Patient demographics were generally similar between treatment groups, but there were more male
patients in the travoprost group.
 Most patients were diagnosed with chronic open-angle glaucoma.
 Study completion rates were high in each group, with 97.4% of patients completing the study as planned.
Dark eye color = brown; light = all other colors.
Mean Diurnal IOP
Mean (± SEM) Diurnal IOP
(mm Hg)
20
Travoprost (N = 135)
Bimatoprost (N = 131)
18
*
16
*
*P ≤ .024 vs travoprost
14
0
Baseline on
Latanoprost
1
2
3
Month After Switch
 Mean diurnal baseline IOPs on latanoprost were similar in the 2 treatment groups.
 After switching from latanoprost, the mean diurnal IOP was significantly lower with
bimatoprost than with travoprost at both month 1 and month 3.
 At month 3, the additional mean reduction from baseline diurnal IOP was
2.1 mm Hg with bimatoprost and 1.4 mm Hg with travoprost (P = .024).
Mean IOP at Each Hour and Visit
9 AM
Mean IOP (mm Hg)
20
4 PM
20
Travoprost (N = 135)
Travoprost (N = 135)
Bimatoprost (N = 131)
Bimatoprost (N = 131)
18
18
*
16
16
*
*P = .004 vs travoprost
*P = .047 vs travoprost
14
14
0
Baseline on
Latanoprost
1
2
Month After Switch
3
0
Baseline on
Latanoprost
1
2
3
Month After Switch
 Baseline mean IOPs on latanoprost were similar in the 2 treatments at each hour.
 After switching from latanoprost, the mean IOP was significantly lower with
bimatoprost than with travoprost at the 9 AM timepoint at month 1 (P = .004) and
the 4 PM timepoint at month 3 (P = .047).
Subgroup Analysis:
Patients With Baseline IOP < 20 mm Hg
Mean Diurnal IOP
Mean (± SEM) Diurnal IOP
(mm Hg)
20
Travoprost (N = 75)
Bimatoprost (N = 70)
18
16
*
*P ≤ .007 vs travoprost
*
14
0
Baseline on
Latanoprost
1
2
3
Month After Switch
 For patients whose baseline IOP on latanoprost was < 20 mm Hg (n = 145),
mean diurnal IOPs were significantly lower with bimatoprost than with travoprost
at both 1 and 3 months.
 At month 3, the mean reduction from latanoprost-treated baseline diurnal IOP
was 1.8 mm Hg with bimatoprost vs 0.5 mm Hg with travoprost (P < .001).
Safety Results
 On biomicroscopy, conjunctival hyperemia and punctate keratitis were the only findings
with ≥ 1-grade increases in severity reported in ≥ 4% of patients in either treatment group.
Percentage of patients with
at least a 1-grade increase
from baseline severity score
 Rates of increased conjunctival hyperemia and corneal staining were low in each group
with no significant difference between groups.
Biomicroscopy Findings
40
Bimatoprost
30
Travoprost
20
17%
11%
10% 10%
10
4%
5%
4%
5%
0
Conjunctival
hyperemia
Corneal punctate
keratitis
Month 1
Conjunctival
hyperemia
Corneal punctate
keratitis
Month 3
 Treatment-related adverse events were reported for only 8.4% of patients in the
bimatoprost group and 6.0% in the travoprost group.
– The incidence of treatment-related ocular or conjunctival hyperemia was 3.1% in the bimatoprost
group and 1.5% in the travoprost group.
Discussion
 A primary goal of glaucoma treatment is to reduce IOP to the target pressure using a
minimal number of medications.1 If the target pressure is not met on initial therapy,
switching to another monotherapy rather than adding a second medication is often
advisable.1 Previous studies have demonstrated that patients uncontrolled on latanoprost
may benefit from switching within the PGA class to bimatoprost or travoprost.2-5
 In this study, baseline mean diurnal IOPs on latanoprost were fairly well controlled at
approximately 19 mm Hg, yet patients achieved mean diurnal IOP reductions of 2.1 mm Hg
with bimatoprost and 1.4 mm Hg with travoprost (P = .024, bimatoprost vs travoprost).
 The decision of whether to switch or add medication may be difficult when the IOP of the
patient is < 20 mm Hg. For patients whose baseline IOP on latanoprost was < 20 mm Hg,
bimatoprost and travoprost provided 1.8 mm Hg and 0.5 mm Hg of mean additional diurnal
IOP lowering, respectively (P < .001). These results suggest that switching to bimatoprost
may be a preferred treatment option for patients on latanoprost who have IOP < 20 mm Hg
yet have not met their target pressure.
 Both study medications were well tolerated. Adverse event reports and biomicroscopic
evaluations showed a low incidence of increased conjunctival hyperemia with each PGA.
 The incidence of hyperemia for patients switched directly from latanoprost to another PGA
is lower than that expected when treatment-naïve patients or patients washed out of
previous medications are initiated on bimatoprost or travoprost therapy. This might be
explained by the development of tolerance during latanoprost treatment.
References: 1. European Glaucoma Society. 2003; 2. Gandolfi and Cimino. Ophthalmology. 2003;110:609-614; 3. Williams. Adv Ther. 2002;19:275-281;
4. Hollo et al. Curr Med Res Opin. 2005;21:1943-1948; 5. Kaback et al. Curr Med Res Opin. 2004;20:1341-1345.
Conclusions
 Switching therapy within the PGA class may allow
patients to reach their target pressure while maintaining
monotherapy.
 The results of this study suggest that for patients on
latanoprost who need lower IOP, switching to bimatoprost
provides greater additional mean diurnal IOP lowering
than switching to travoprost.
 Additional IOP lowering was observed after the switch to
bimatoprost, even at relatively low latanoprost baselines.
 The rate of increased hyperemia is low in patients
switched directly from latanoprost to either bimatoprost or
travoprost.