Efficacy of CAI in Addition to Fixed Combination Therapy

Commonly, the second medication class after a prostaglandin analogue is a beta-blocker that can either be used adjunctively or within a fixed combination product. If this proves inadequate as well, further medication usually consists of either an alpha-agonist or a topical carbonic anhydrase inhibitor (CAI). There is little evidence on the efficacy of adding a third agent to an ongoing prostaglandin and beta-blocker combination. We examined the efficacy of brinzolamide, a topical CAI, when added to travoprost/timolol fixed combination (TTFC) therapy and compared it with a placebo control.¹

Methods

All patients initially included in the study underwent a screening examination, consisting of Goldmann applanation tonometry, Snellen visual acuity at 6 metres and slit lamp biomicroscopy. These examinations were performed at alternate visits.

During this initial visit, patients meeting inclusion and exclusion criteria, were changed to TTFC combination dosed each morning for 4 weeks when they returned for the day 0 baseline examination. Patients with an IOP from 19 to 32 mmHg inclusive at 8 am had baseline diurnal IOP measurements at midday and 4 pm. Qualified patients were then randomized to either receive brinzolamide or placebo (brinzolamide vehicle) in addition to their TTFC; the add-on drops were administered with one drop in the study eye(s) at 8 am and 8 pm. At week 4, IOP was measured again at 4 pm and safety evaluated. During week 12, the patients had their IOP measured at 8 am, then the morning dose of TTFC followed at least 5 minutes later by the masked study medicine was instilled. IOP was measured at midday and at 4 pm.

Results

Patient demographics (age, gender, ethnicity, past medical history) were not statistically significantly different between the two treatment arms.

We found a decrease from baseline diurnal IOP at all times for both brinzolamide and placebo arms. However, there was a larger decrease seen in the brinzolamide group and at all times the IOPs for this group was lower than that for the placebo group. Brinzolamide reduced the mean diurnal IOP from 20.3±2.0 to 17.5±2.6, whereas in the placebo group, IOP fell from 20.9±2.7 to 19.4±3.8.

As we recorded 30 adverse events in our placebo treatment arm and 24 in the brinzolamide arm, we concluded that there was no statistical difference in side-effect profile between our groups. There were two serious adverse events in the placebo arm but these were considered to be unrelated to the medications. Two patients discontinued treatment in the placebo arm because of itching and lid darkening; in the brinzolamide group, one patient discontinued treatment as a result of mild anterior uveitis.

Discussion

We demonstrated a significant reduction in diurnal IOP at every time measured with the addition of brinzolamide as third medical agent to treatment with a TTFC combination for patients with OHT or POAG. As there are few studies assessing three-drug therapy in glaucoma patients, these results are helpful for clinicians to achieve a further significant reduction in IOP. No major safety concerns were raised.

Based on the results of this study, brinzolamide may be added to ongoing TTFC combination therapy with expectation of a further potentially significant reduction in diurnal IOP. This study did not evaluate long-term visual outcomes or costs of management.

Authors

Professor Ivan Goldberg is clinical associate professor at the University of Sydney, head of the Glaucoma Unit at Sydney Eye Hospital, and director, Eye Associates, Sydney, Australia. He may be reached by Email: eyegoldberg@gmail.com

Prof. Goldberg has indicated he is a consultant/board member for Alcon, Allergan, ForSight; a speaker at symposia sponsored by: Alcon, Allergan, Pfizer; and has received travel support from Alcon, Allergan, Pfizer.

Dr Jay Yohendran is a clinical lecturer at the University of Sydney and Ophthalmologist at Royal Prince Alfred Hospital, Sydney, Australia, and in private practice. He may be reached by Email: jay@gmp.usyd.edu.au
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Dr Yohendran has indicated no financial interests in the subject matter.

Reference

1. I. Goldberg et al., J. Glaucoma, 2012;21(1):55–59.