STUDY DETAILS
Methodology
The 6-month, multicenter, randomized, parallel-group comparison, double-masked clinical trial was conducted at 18 investigational centers in the US and enrolled 269 patients needing bilateral ocular hypotensive treatment. All subjects had a BCVA of 20/100 or better in each eye and had not exhibited significant or progressive visual field loss over the preceding year. We measured subjects' IOPs with Goldmann applanation tonometry at 8 AM during the baseline visit. All patients had pressure values of between 22 and 34 mm Hg and a difference of no more than 5 mm Hg between their eyes.
Following a washout period that lasted between 4 days and 8 weeks (depending on which medication patients were taking prior to the study), we randomly assigned subjects to treatment with either bimatoprost or latanoprost every evening. The two study groups were well matched at baseline in terms of age (mean of approximately 61 years), gender (approximately 60% female), race, iris color, primary diagnosis (approximately 55% primary open-angle glaucoma), and proportion on prior ocular hypotensive therapy (approximately two-thirds of subjects).
We performed IOP measurements at 8 AM, 12 PM, and 4 PM, with the value obtained at least twice and repeated a third time if the two values were not within 2 mm Hg of each other. Data for both eyes were averaged using either the mean of two obtained IOP values or the median of three values. The baseline mean IOP was comparable in the bimatoprost and latanoprost groups at 8 AM (25 vs 24.9 mm Hg, respectively) and 4 PM (22.6 vs 22.5 mm Hg, respectively), but it was significantly higher in the bimatoprost versus latanoprost eyes at 12 PM (24 mm Hg vs 23.3 mm Hg). For that reason, we conducted the 12 PM statistical analysis using analysis of covariance, which accounts for differences in baseline values, but analyzed the other time points using analysis of variance. Of the 269 patients enrolled in the study, 249 (93%) completed 6 months of treatment. Only one patient withdrew early due to a lack of efficacy, and that individual was in the latanoprost group.
Results
The primary outcome measure was the mean change from baseline at 8 AM, 12 PM, and 4 PM. Other endpoints determined prospectively included the mean IOP, percentage of patients reaching specific target pressures, and percentage of patients achieving at least a 15% or 20% reduction in IOP.
The results from follow-up at 1 week and 1, 3, and 6 months of treatment showed that both drugs lowered IOP from baseline significantly. Bimatoprost, however, lowered IOP more from baseline than did latanoprost by statistically significant margins of between 0.9 to 2.2 mm Hg at all time points throughout the day. Data from the 6-month visit showed that the mean pressure reductions achieved from the 8 AM, 12 PM, and 4 PM baseline IOP values were 1.2 to 2.2 mm Hg greater in the bimatoprost group compared with the latanoprost group. Mean IOP values throughout the day ranged from 16.5 to 17.4 mm Hg in the bimatoprost group, compared with 17.6 to 18.9 mm Hg in the latanoprost group. At each measurement time, bimatoprost was associated with a significantly lower mean IOP compared with latanoprost.
Bimatoprost was also superior in the other secondary efficacy measures of mean IOP, percentage of patients reaching specific target IOP levels, and responder rates (percentage of patients achieving a greater than 15% or 20% reduction from baseline). With patients stratified by proportions achieving different target IOPs between 13 and 20 mm Hg, the rates were consistently numerically higher in the bimatoprost group, and, for the majority of pair-wise comparisons, the differences were statistically significant. At month 6, the 8-AM, 12-PM, and 4-PM measurements showed an IOP reduction to a target of at least 15 mm Hg among 20% to 36% of bimatoprost patients compared with 18% to 25% of patients treated with latanoprost.
In our analysis of responder rates, between 83% and 89% of patients in the bimatoprost group achieved a 15% or greater decrease from their baseline IOP across the three IOP measurement times, and the responder rates based on the more stringent criteria of a 20% or greater reduction were 69% to 82%. For latanoprost, 65% to 72% of patients achieved a 15% or greater reduction from their baseline IOP, and 50% to 62% experienced IOP lowering of 20% or more.
The study showed that there were no safety problems with either drug, and adverse events were ocular in nature. The side effects of conjunctival hyperemia, eyelash growth, and ocular pruritus were significantly more common in patients treated with bimatoprost compared with patients using latanoprost. The rate of hyperemia reported at any visit was 44.4% for bimatoprost-treated patients and 20.6% for latanoprost-treated patients. The higher occurrence rate of these side effects did not lead to a higher rate of discontinuation for patients who were taking bimatoprost, however. In fact, the discontinuation rates were similar between the bimatoprost and latanoprost groups, 4.5% versus 3.7%, respectively.
PERSPECTIVE ON THE STUDY
Our further subgroup analysis showed no differences between subjects who either were or were not taking latanoprost prior to the trial regarding outcomes. Of the subjects washed out of latanoprost prior to the study, there were 38 in the bimatoprost group and 30 randomized to latanoprost. Also, some representatives of Pharmacia Corporation have noted that the responder rate for patients taking XALATAN appears to be low. A review of the literature, however, reveals a 20% responder rate as the median reported in studies and 30% as the average.2,3 It is also important to recognize that the study described in this article defined the responder rate as that percentage of patients on medication who did not achieve at least a 20% IOP reduction from baseline, rather than as zero responses. A patient who had an IOP of 26 mm Hg at baseline may have experienced a 5-mm Hg drop in eye pressure, but this decrease would not have hit the threshold of a 20% reduction; the patient would therefore not have been defined as a responder, per study design.
This large-scale, well-designed study confirms the results of previous head-to-head comparative trials (involving smaller numbers of subjects and shorter treatment durations) that indicated that bimatoprost provides better IOP control than latanoprost. Whether looking at efficacy based on the mean change from baseline at various times throughout the day or using other criteria, the study data are consistent in demonstrating the greater efficacy of bimatoprost, and that uniformity across all methods of analysis is reassuring.
Furthermore, rates of hyperemia and ocular itching with bimatoprost are not surprising, because they corroborate previous clinical and study experience. Although these side effects are not dangerous, they do occur and are issues that must be addressed by the clinician. These reactions are transient and self-limiting, and, as long as ophthalmologists set patient expectations prior to initiating treatment, the occurrence of side effects can be minimized.
CONCLUSION
The consensus in treating glaucoma is that it is best to lower the IOP as much as possible. The EMGT showed us that, for every 1 mm Hg by which the IOP was lowered, there was a 10% drop in the patient's risk of glaucoma progression.4 Newer drugs such as latanoprost and bimatoprost allow clinicians to achieve lower IOPs with medical therapy than previously possible. The results of this study indicate that, whether ophthalmologists are aiming for a specific, low target pressure or a particular percentage reduction from baseline, they can more predictably achieve their therapeutic goal using bimatoprost than latanoprost.
Robert J. Noecker, MD, is Associate Professor of Ophthalmology and Director of the Glaucoma Service, Residency Program, and Clinical Studies Program at the University of Arizona in Tucson, Arizona. This study was sponsored by Allergan, Inc. Dr. Noecker holds no proprietary interest in either product mentioned herein but does receive research funding from both Pharmacia Corporation and Allergan, Inc. He may be reached at (520) 321-3677; rnoecker@eyes.arizona.edu.
1. Noecker RS, Dirks MS, Choplin NT, et al. A six-month randomized clinical trial comparing the intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma. Am J Ophthalmol. 2003;135:55-63.
2. Martin L. Clinical experience with latanoprost: a retrospective study of 153 patients. Acta Ophthalmol Scand. 1999;77:336-339.
3. Aung T, Chew PT, Yip CC, et al. A randomized double-masked crossover study comparing latanoprost 0.005% with unoprostone 0.12% in patients with primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 2001;131:636-642.
4. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120:10:1268-1279.
