Article Date: 8/1/2006

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Travoprost Develops a Strong Track Record for Safety and Efficacy

New studies show travoprost lowers IOP and sustains lasting effects. These findings and others that show travoprost's efficacy and safety may encourage clinicians to use the drug in more patients to promote better outcomes.
By Judith Springer Riddle, Senior Editor

New data on the safety and efficacy of travoprost 0.004% (TRAVATAN® solution) show this agent sustained lower IOPs than latanoprost 0.005% (XALATAN*) in glaucoma patients throughout a 24-hour period and beyond.

Other research found that travoprost had lasting effects on diurnal and nocturnal IOP even after it was discontinued for 41 to 63 hours.

One particular carbonic anhydrase inhibitor, when added to travoprost therapy, showed excellent additivity in lowering IOP.

In a large clinical study (n=690), a travoprost BAK-free formulation was shown to have equivalent IOP-lowering efficacy to the currently marketed travoprost 0.004%.

Here are the specifics of these latest study findings that could lead to better visual outcomes in glaucoma patients:

Lasting effects of travoprost on diurnal and nocturnal intraocular pressure

Recent studies suggest the IOP-lowering effects of prostaglandin analogues can persist well beyond the standard 24-hour dosing schedule.

To confirm these findings, Sit, Weinreb and colleagues investigated the diurnal and nocturnal persistence of IOP reduction after discontinuing one or two doses of travoprost in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). In this prospective, open-label study, 20 patients underwent three 24-hour sessions of IOP monitoring. The first (baseline) session occurred before therapy was initiated in newly diagnosed patients or after a 4-week washout period for those switching to travoprost. Patients administered travoprost 0.004% to both eyes once daily at bedtime.

A second monitoring session occurred after 4 weeks or more of travoprost treatment. One to 8 weeks later, a third session was performed 41 to 63 hours after the last travoprost dose.

At all times throughout the second and third 24-hour monitoring periods, IOPs on treatment and off treatment were lower than the corresponding baseline IOPs.

IOP reduction was sustained 41 to 63 hours after eliminating one to two doses of travoprost.

Researchers believe these findings may result from persistent structural and biochemical remodeling in the uveoscleral outflow pathway.

Sit AJ, Weinreb RN, Crowston JG, et al. Sustained effect of travoprost on diurnal and nocturnal intraocular pressure. Am. J Ophthalmol. 2006;141:1131-1133.

Travoprost sustains lower IOP readings than latanoprost over a 24-hour period

In this study, researchers compared travoprost 0.004% to latanoprost 0.005% to determine which prostaglandin analogue was better at sustaining lower IOP readings over a 24-hour period in patients with OAG or OHT.

During the patient eligibility visit, investigators measured IOPs every 4 hours throughout a 24-hour period. They randomized 62 patients to receive either one drop of travoprost (n=32) or latanoprost (n=30) each evening for 2 weeks. At week 2, investigators measured IOPs every 4 hours throughout two consecutive 24-hour periods.

The results: Travoprost produced lower mean IOPs than latanoprost at all time periods, and IOPs were significantly lower for the travoprost group at 12, 16, 20, 24, 36, 40 and 48 hours after the last dose.

Feijoo JG, Martinez-de-la-Casa JM, et al. A Comparison of the IOP Lowering Efficacy of Travoprost 0.004% and Latanoprost 0.005% Over a 24 Hour Period. Presented at The Association for Research in Vision and Ophthalmology; April 30-May 4, 2006; Fort Lauderdale, FL.

Travoprost and latanoprost: efficacy vs. safety

Travoprost 0.004% was compared with latanoprost 0.005% in this prospective comparison study to measure safety and efficacy in lowering IOPs over a 24-hour period in exfoliative glaucoma patients.

In this trial, 40 patients with IOPs of 24 mm Hg or higher were randomized to receive either latanoprost or travoprost for an 8-week treatment period. Subjects were then switched to the opposite treatment for another 8 weeks. At baseline and at the end of each treatment session, researchers assessed IOP readings for 24 hours at 6 a.m., 10 a.m., 2 p.m., 6 p.m., 10 p.m. and 2 a.m.

Researchers found that travoprost produced significantly lower IOPs throughout the 24 hours and a statistically lower pressure at 6 p.m.

Konstas A, Vassilios KP, Ioannis KE, et al. 24-hour IOP Efficacy and Safety of Latanoprost 0.005% versus Travoprost 0.004% Each Given Every Evening in Exfoliative Glaucoma Patients. Presented at the World Ophthalmology Congress; February 19-24, 2006; Saõ Paulo, Brazil (submitted for publication).

A comparison of brinzolamide 1% vs. brimonidine 0.15% when added to travoprost in glaucoma patients

Although it's common practice to add carbonic anhydrase inhibitors and alpha2 agonists to prostaglandin analogues to lower IOPs in glaucoma patients, few studies have been done to confirm their additive effects.

Feldman and colleagues conducted the first prospective, double-masked study to compare the efficacy of brinzolamide 1% (AZOPT® suspension) and brimonidine 0.15% (ALPHAGAN* P) when added to travoprost 0.004% in glaucoma patients.

Researchers studied the effects of each drug when added to travoprost in 163 patients, age 35 years and older, at 17 centers. Seventy-nine patients were given brimonidine 0.15%, while 84 received brinzolamide 1% twice a day for 3 months in addition to travoprost.

Results showed patients receiving brinzolamide 1% achieved a mean diurnal IOP decrease of 2.9 mm Hg at 3 months versus 2.1 mm Hg in patients receiving brimonidine 0.15% (p=0.035).

Researchers concluded that adding brinzolamide to travoprost lowers IOP more so than adding brimonidine at 8 a.m., 4 p.m. and diurnal.

Feldman RM, Prager TC, et al. Additivity of Brinzolamide vs. Brimonidine 0.15% to Travoprost 0.004%. Presented at The Association for Research in Vision and Ophthalmology; April 30-May 4, 2006; Fort Lauderdale, FL.

Comparison of travoprost with and without BAK for safety and efficacy

Benzalkonium chloride (BAK) has long been known for lowering the risk of bacterial contamination in glaucoma medications, thus increasing their shelf life. But its propensity to cause ocular damage in patients continues to spur introductions of new preservative-free drug formulations.

In a recent double-masked, randomized multicenter trial, investigators compared the safety and efficacy of the newly formulated travoprost 0.004% made without BAK to the currently marketed travoprost 0.004% containing the preservative in patients with open-angle glaucoma or ocular hypertension.

Adult patients with OAG or OHT with IOPs of 24 mm Hg to 36 mm Hg at 8 a.m., and 21 mm Hg to 36 mm Hg at 10 a.m. and 4 p.m., in at least one eye, received either travoprost 0.004% preserved with BAK (n=346) or travoprost BAK-free (n=344) once daily in the evening.

Researchers measured IOPs at 8 a.m., 10 a.m. and 4 p.m. at week 2, week 6 and month 3 of the study. Mean IOP reductions across nine study visits ranged from 7.3 mm Hg to 8.5 mm Hg for travoprost BAK-free and from 7.4 mm Hg to 8.4 mm Hg for travoprost 0.004%.

The number of adverse events and the patients who discontinued therapy because of them were similar for both treatment groups. The study reported 6.4% of subjects treated with travoprost BAK-free experienced hyperemia. Researchers concluded travoprost BAK-free was equivalent to travoprost 0.004% in both safety and efficacy.

Lewis RA, Weiss MJ, Landry TA, et al. Travoprost 0.004% With and Without Benzalkonium Chloride: A Comparison of Safety and Efficacy. Presented at The Association for Research in Vision and Ophthalmology; April 30-May 4, 2006; Fort Lauderdale, FL.

Travoprost lowers IOP better than latanoprost in a 6-week comparison, open label study

At the 2006 annual meeting of the American Glaucoma Society, Maul and colleagues presented the results of a randomized, double-masked study that compared the IOP-lowering efficacy and safety of travoprost 0.004% with latanoprost 0.005% when dosed once daily for 6 weeks in patients with OAG or OHT.

For 6 weeks in this study, 155 patients received travoprost 0.004% while 147 patients received latanoprost 0.005%.

The medications were administered once daily at 9 p.m. Researchers measured IOPs at 5 p.m. This 6-week study included visits at screening, eligibility and during weeks 1, 2, 4 and 6.

Mean IOP values were lower for travoprost at all time points during the study. Differences in mean IOP change from baseline for the four on-therapy visits all favored travoprost. The difference in pooled IOP reductions from baseline was statistically significant: 8.3 mm Hg for travoprost and 7.5 mm Hg for latanoprost during the masked phase of the study.

Researchers found that travoprost 0.004% produced significantly greater IOP-lowering effects compared to latanoprost 0.005% at 5 p.m., approximately 20 hours after dosing.

Maul E, Carrasco FG, Costa VP, et al. A Six-Week Double-Masked Study Comparing Travoprost 0.004% to Latanoprost 0.005% Followed by a Six-Week Open-Label Treatment on Travoprost 0.004%. Presented at the American Glaucoma Society annual meeting, March 2-5, 2006, Charleston, SC.



Optometric Management, Issue: August 2006