Comparison study: brimonidine fares well as add-on therapy

January 15, 2008

In a comparison study of adjunctive medication for glaucoma therapy, the addition of brimonidine tartrate, a selective alpha-adrenergic agonist, to a prostaglandin analog achieved greater pressure-lowering than either of two carbonic anhydrase inhibitors.

Key Points

New Orleans-The addition of brimonidine tartrate 0.15 % (Alphagan P, Allergan) to a prostaglandin analog resulted in significantly greater reductions in IOP than the use of either dorzolamide 2% (Trusopt, Merck) or brinzolamide 1% (Azopt, Alcon Laboratories) as an adjunctive medication in glaucoma therapy, according to a recent study.

More than twice as many patients consistently achieved low IOPs with adjunctive brimonidine than with either of the other drugs, said Thomas Bournias, MD, who presented his findings in a poster here at the annual meeting of the American Academy of Ophthalmology. He is assistant clinical professor, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago.

As a glaucoma specialist and someone who likes to study the behavior of drugs and other treatments, Dr. Bournias wanted to study which drugs should be used as adjuncts to first-line therapy.

The customary options are beta-blockers, carbonic anhydrase inhibitors (CAIs), and alpha-adrenergic agonists. A consensus exists among many ophthalmologists that beta-blockers are less effective when added to prostaglandin analogs than when used alone or in conjunction with other types of drops, Dr. Bournias said. Little published data exist on the relative efficacy of brimonidine or the CAIs when used as adjunctive therapy to prostaglandin analogs, however.

With that in mind, he designed a randomized, prospective, single-center, investigator-masked, parallel-group study to compare the potency of two CAIs and an alpha-adrenergic agonist when used as adjunctive therapy to a hypotensive lipid.

Study methodology

The study enrolled 120 patients with glaucoma or ocular hypertension diagnosed who had inadequate pressure control (IOP > 18 mm Hg) on monotherapy with a once-daily prostaglandin analog. The primary therapy in the study eye was bimatoprost (Lumigan, Allergan; n = 71), latanoprost (Xalatan, Pfizer; n = 35), or travoprost (Travatan, Alcon; n = 14); primary therapy had begun at least 6 weeks prior to the baseline examination.

The eyes were randomly divided into three treatment groups: brimonidine (n = 41), dorzolamide (n = 40), and brinzolamide (n = 39). The adjunctive drugs were dosed at 8 a.m., 4 p.m., and 10 p.m. for 4 months. The prostaglandin analog was dosed between 8 and 10 p.m. through the study period. Study visits occurred at baseline, month 1, and month 4.

Peak and trough IOP measurements were taken. The peak effect was measured at 10 a.m., 2 hours after an adjunctive medication dose, and the trough effect was measured at 4 p.m., just before an adjunctive medication dose. The statistical analyses consisted of the chi-square test for categorical variables and analysis of variance for IOP.

Further IOP reductions from baseline were observed for patients taking all three adjunctive medications; however, brimonidine provided significantly lower mean IOP than dorzolamide and brinzolamide and significantly greater additional IOP-lowering at both the 10 a.m. and 4 p.m. time points at each follow-up visit, Dr. Bournias said.

Patients treated with adjunctive brimonidine were more than twice as likely to achieve consistently lower IOP in their study eye. Diurnal IOP was less than 18 mm Hg at both follow-up visits for 87.8% of patients taking brimonidine, 36.0% of patients taking dorzolamide, and 33.3% of patients taking brinzolamide.

In addition, the eyes treated with brimonidine achieved about a 1 to 1.5 mm Hg further mean IOP reduction than eyes dosed with either of the adjunctive CAIs, he added.

"The significance of this is that when you have a large population and you lower pressure, on average, by another point or point and a half, that will have ramifications for the patient pool, in that many of them will have a much greater response," he said.

Dr. Bournias did not break down the results by comparing outcomes between the three prostaglandin analogs and the three adjunctive medications. The travoprost group had too few eyes to achieve valid results, he said, adding that he planned to analyze the outcomes for latanoprost and bimatoprost.