Brimonidine/timolol fulfills criteria for good adjunctive therapy, data show

January 15, 2008

Two Canadian multicenter, randomized trials compared fixed-combination treatment with 0.2% brimonidine/0.5% timolol against 2.0% dorzolamide/0.5% timolol.

Key Points

New Orleans-Analyses of pooled data from two identical Canadian multicenter studies demonstrated that fixed-combination treatment with 0.2% brimonidine/0.5% timolol (Combigan, Allergan) as mono- or adjunctive therapy was significantly more comfortable than 2.0% dorzolamide/0.5% timolol (Cosopt, Merck) and provided equal or superior IOP-lowering efficacy, reported Donald R. Nixon, MD, here at the American Academy of Ophthalmology annual meeting.

"These findings corroborate previous studies demonstrating the IOP-lowering efficacy and comfort of [brimonidine/timolol] and validate the usual clinical practice pattern of Canadian ophthalmologists who have had access to this fixed-combination agent for about 3 years," said Dr. Nixon, Trimed Eye Centre, Barrie, Ontario.

"Approximately 30% of Canadian patients being treated with IOP-lowering medications are taking a fixed combination. During the time [brimonidine/timolol] has been available in Canada, it has become a fundamental component of glaucoma therapy, where it has achieved a high position in the treatment algorithm used both as monotherapy and as an adjunct to a prostaglandin analogue," he told Ophthalmology Times.

Mean IOP was statistically equivalent in the two treatment groups at baseline, and both groups had a significant decrease in IOP at the first follow-up by 1 month. At 3 months, mean IOP was significantly lower, at 15.6 mm Hg, in the brimonidine/ timolol group than the mean IOP of 17.2 mm Hg in the dorzolamide/timolol-treated patients.

Subgroup analyses for the patients being treated with the fixed combination as adjunctive therapy showed that the mean decrease from baseline IOP in the brimonidine/timolol group was 6.9 mm Hg, or a 29% reduction from baseline. Brimonidine/ timolol monotherapy resulted in a 7.7-mm Hg mean lowering of IOP.

The study participants also completed a comfort-and-tolerability questionnaire, and the majority of patients rated the fixed combination of brimonidine/timolol as "comfortable" or "very comfortable." In addition, they were asked to evaluate and grade their symptoms of burning, stinging, and taste after instillation of the fixed combination that they were using. Patients graded individual symptoms on a scale from 0 to 4 (0 = no symptoms, 4 = severe), and the results showed that use of brimonidine/timolol was associated with significantly less stinging, burning, and unusual taste compared with dorzolamide/ timolol.

The differences in adverse symptoms are consistent with previous reports and reflect the pH-related consequences of the dorzolamide/timolol formulation when it is instilled onto the ocular surface and as the medication drains into the nose and oral pharynx. These issues can have an important effect on tolerability and compliance in clinical practice, Dr. Nixon observed.

"It doesn't matter how efficacious a medication is; if it is not tolerable, the patient will not use it. Brimonidine/timolol has a favorable comfort profile that may be expected to enhance compliance, and compliance has a direct effect on medication efficacy," he said.

The objective in designing the protocol for the two studies, Dr. Nixon said, was to compare the efficacy and tolerability of the fixed-combination agents in a study that would reflect routine clinical practice. Results from studies that really reflect clinical practice patterns, such as this one, tend to have a greater clinical relevance to the practicing ophthalmologist, he added.

"Canadian ophthalmologists are pretty comfortable stopping an alpha-adrenergic agonist, beta-blocker, or carbonic anhydrase inhibitor to start a fixed-combination treatment, and they would use a fixed combination as an adjunct to a prostaglandin analogue but would be unlikely to use it as a substitute," he said.

The IOP analyses showed that 3 months of treatment with brimonidine/timolol resulted in an almost 30% or greater reduction from baseline IOP whether it was used as mono- or adjunctive therapy. With this demonstrated efficacy and mechanisms of action, brimonidine/timolol fulfills the criteria for a good adjunctive therapy, Dr. Nixon said.