Mean changes from baseline intraocular pressure were 0.9 mm Hg to 2.2 mm Hg greater with bimatoprost (Lumigan, Allergan) than with latanoprost (Xalatan, Pharmacia) in a multicenter, randomized, masked clinical trial. The greater IOP lowering efficacy of bimatoprost relative to latanoprost also was confirmed by the mean IOP, which was statistically significantly lower in the bimatoprost group at all time points on all follow-up visits, according to lead investigator Robert J. Noecker, MD. The study, which was sponsored by Allergan, appears in this month’s edition of the American Journal of Ophthalmology.
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“The purpose of this large, six-month study was to see if, in fact, there is a difference between the drugs in a well-controlled comparison of the same population groups,” Noecker said. “The primary outcome measure was mean change from baseline IOP at three daily time points: 8 a.m., noon, and 4 p.m. “IOP was measured throughout the day because both of these drugs have long half-lives, and Lumigan was superior at every single time point,” Noecker said. “When we looked at other measures like ending mean IOP, we saw basically the same story,” he said.
A group of 269 patients between the ages of 24 and 88 were seen at 18 locations across the country. Baseline IOP measurements were taken following a medication washout period of four days for parasympathomimetics and carbonic anhydrase inhibitors; two weeks for sympathomimetics and alpha-agonists; four weeks for beta blockers; and eight weeks for prostaglandins and prostamides. At baseline, IOPs were between 22 mm Hg and 34 mm Hg with asymmetry in IOP between eyes of no more than 5 mm Hg.
Mean change from baseline IOP was statistically significantly greater for bimatoprost patients than for latanoprost patients at all measurements on each study visit; 1.5 mm Hg greater at 8 a.m. (P<0.001), 2.2 mm Hg greater at noon (P< 0.001) and 1.2 mm Hg greater at 4 p.m. (P=0.004). The percentage of patients achieving greater than or equal to 20% IOP reduction was 69% to 82% with bimatoprost and 50% to 62% with latanoprost, at the end of the study.
Confirmatory studies needed
Some say the study needs further support before such claims can be accepted. “The data are quite strong and consistent with much of my clinical experience, however, it is a single study and needs to be confirmed in other investigations,” said Louis B. Cantor, MD, professor of ophthalmology and director of glaucoma service, Indiana University, Indianapolis. He added that although further trials may be necessary to confirm the findings, “the study provides compelling evidence for a difference.”
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Paul Palmberg, MD, professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami (Fla.), also would like to see another trial to test the conclusions reached in Noecker’s study. “In two previous Allergan-sponsored studies, (DuBiner H, Survey of Ophthalmology, 2001 and Gandolfi S., Adv Ther 2001), there was no significant difference (30% vs. 32% IOP reduction) in the effectiveness of Xalatan and Lumigan at 8 a.m. when the baselines were nearly equal,” he said. “So it is puzzling that this new paper shows only a 24% reduction with Xalatan vs. 32% with Lumigan. Also, three previous studies of Xalatan in similar patients showed a much better average pressure lowering (28% to 35%), and no other study has ever shown such a high rate of poor responders. Any time you get an outlier result to all the rest of the literature – even in a well-run, randomized, trial – you have to have another study in a different group of patients to confirm the result.”
Palmberg suggested previous nonresponders, problems with masking, or statistical problems as possible confounding factors. Scatter plots detailing the outcomes of patients who were previously on Xalatan as well as those who had hyperemia would provide additional information that might account for the study’s variation from earlier studies comparing bimatoprost to latanoprost, he said.
“Some people say all these drugs are the same; that there’s no efficacy difference between Xalatan and Lumigan even though smaller studies have hinted at a difference,” Noecker said. “I think the prostaglandins, Travatan and Xalatan, are pretty much the same. They work from the same receptor; they’re doing the same thing. Lumigan, on the other hand, is a prostamide, which appears to work differently.”
Although the existance of a prostamide receptor has been controversial, Noecker hypothesized that this is what accounts for the study’s results.
“Nobody really knows why bimatoprost did better, but we hypothesize that probably the effect of Lumigan is that it works on the uveoscleral outflow – just as the prostaglandins do, but that there also seems to be a significant component of trabecular outflow, and perhaps it’s digesting the extracellular matrix protein in the trabecular meshwork, and that’s what accounts for the additional efficacy,” he said.
Contact Information Cantor: 317-274-8485, fax 317-278-1007 Noecker: 520-321-3677, fax 520-321-3665 Palmberg: 305-326-6386, fax 305-666-2117 |