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Travoprost with less toxic preservative causes less ocular surface toxicity

In a pooled dataset, the fixed combination of 0.2% brimonidine/0.5% timolol (Combigan, Allergan) showed greater reductions in IOP and a better tolerability profile than another combination agent, 2.0% dorzolamide/0.5% timolol (Cosopt, Merck). The twin advantages of greater pressure lowering and greater tolerability could help guide clinicians in choosing which therapy to choose when the initial treatment has not resulted in adequate improvement.

Key Points

Singapore-In a pooled data set, the fixed combination of 0.2% brimonidine/0.5% timolol (Combigan, Allergan) showed greater reductions in IOP and a better tolerability profile than another combination agent, 2.0% dorzolamide/0.5% timolol (Cosopt, Merck).

The directed phase IV study was designed to follow up more rigorously on the trends identified in previous studies, according to Donald R. Nixon, MD, senior consultant, Department of Ophthalmology, Royal Victoria Hospital, Barrie, Ontario.

Two previous studies (Combigan Early Experience Data Trial, parts I and II) compared those fixed combination agents, and both indicated that the brimonidine/timolol combination was more advantageous. Both studies, although having a large number of participants, were limited by being unmasked or open label.

Clinicians in Canada have had access to the brimonidine/timolol combination for more than 2 years, and the agent met early acceptance, Dr. Nixon noted. He explained that use of the combination offered more benefits than use of two separate agents because of the dual mechanism of action and greater convenience of single dosing, which enhanced patient compliance.

In Canada, if initial monotherapy with a prostaglandin analog fails to achieve an adequate reduction in IOP, the accepted protocol is to switch to another prostaglandin analog prior to adding another agent, such as a drug from a different category or a fixed combination.

"However they get there, in Canada, a significant percentage of patients end up being treated with a fixed-combination medication in conjunction with a prostaglandin analog, so this study really represents clinical practice," Dr. Nixon said. What resulted from the desire to obtain more scientifically valid data on the two combination agents was a pair of randomized, investigator-masked, 3-month parallel comparison studies of efficacy and tolerability. The studies were conducted at 10 sites in Canada with identical protocols.

In a poster presentation at the World Glaucoma Congress meeting, Dr. Nixon released pooled data from the studies, which enrolled 180 patients with ocular hypertension or open-angle glaucoma who required additional lowering of their IOP levels.

A small percentage of the patients were naïve to therapy, and they were randomly assigned to either of the two combination agents. Most patients, however, had preexisting disease and were receiving therapy such as beta-blockers, alpha-adrenergics, or carbonic anhydrase inhibitors. After wash-out, patients were randomly assigned to a combination medication. A third group consisted of patients who may have been taking a prostaglandin analog and another medication. All medication was washed out except the prostaglandin analog, then patients were randomly assigned to one of the combination therapies. Ultimately, 101 patients were assigned to a fixed combination and 79 to prostaglandin analog.

"The end result at 3 months was that there was a statistically significant advantage in pressure lowering effect for brimonidine/ timolol over dorzolamide/timolol," Dr. Nixon said. "The other thing that was quite interesting [was] that if you take a look at the subgroup that started with a prostaglandin analog and then brimonidine/timolol was initiated, there was a very impressive reduction in pressure, suggesting that the combination of the prostaglandin analog with the brimonidine/timolol showed a significant therapeutic advantage."

In another important outcome of the study, the brimonidine/timolol combination agent also was rated more highly on a patient tolerability questionnaire. The survey was administered at 1 month to assess symptoms of stinging, burning, and unusual taste on a scale of 0 to 5 and was scored independently.

"There was statistically less stinging, less burning, and less bad taste with the brimonidine/timolol," Dr. Nixon said. That advantage persisted over the duration of the study, he added.

The twin advantages of greater pressure lowering and greater tolerability could help guide clinicians on which therapy to choose when the initial treatment has not resulted in adequate improvement, Dr. Nixon continued.

A paper about the study is being submitted for publication.

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