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Fixed combination travoprost/timolol offers convenience, efficacy
Study shows fixed combination therapy offers more convenience, slightly less efficacy than concomitant dosing.
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SARASOTA, U.S.A. – A fixed combination of travoprost 0.004% and timolol 0.5% offers glaucoma patients greater convenience with similar efficacy compared to the two components taken concomitantly, according to a surgeon speaking at the meeting of the American Glaucoma Society.
Although investigators saw a small additional IOP-lowering benefit to concomitant administration of the two components, Joel S. Schuman, MD, who presented the study results, noted that the possibility of increasing compliance and reducing costs might have greater clinical value.
The study, one of three phase 3 clinical trials for Alcon’s Travatan/Timolol Fixed Combination, or Extravan solution, compared the drug taken once in the morning to the concomitant administration of timolol in the morning and Travatan (travoprost, Alcon) in the evening.
Patients taking timolol in both the morning and evening served as a control group.
Results
The study found that Extravan lowered baseline IOP by 29% to 33%. In patients with pressures ranging from 22 mm Hg to 36 mm Hg at entry, this reduction translated into an improvement of 6.8 mm Hg to 8.6 mm Hg.
The two test groups showed no significant difference in IOP at the 8 a.m. time point. In four of the five additional time points, however, concomitant administration yielded an IOP improvement that was about 1 mm Hg lower than combination therapy.
Dr. Schuman told Ocular Surgery News that the difference, while statistically significant, might be outweighed by the convenience, compliance and possible cost benefits of the fixed combination. He compared Extravan to Cosopt (dorzolamide and timolol, Merck), the first combination therapy among the current generation of glaucoma drugs to receive U.S. Food and Drug Administration approval.
“There’s a real analogy to Cosopt, where we saw the same sort of efficacy issues; the concomitant use of the components was a little bit more effective in reducing IOP than the combination drop,” he said. “But Cosopt has been a real boon to ophthalmologists who were able to treat their patients and to get better compliance, perhaps because of the convenience that’s offered to these patients.”
Real-world compliance
He also noted that the results were obtained under ideal conditions; patients enrolled in a clinical trial are generally more compliant than patients who are treated under other circumstances.
Dr. Schuman cited a study by Choudhri and colleagues that found a greater effect from combination therapies than concomitant administration of the components. “Studies that have been done in real world settings show something a little bit different” than the phase 3 clinical trials, he said.
Combination therapies eliminate the possibility of a washout effect when patients do not wait the necessary amount of time between drops. In addition, they have the potential to reduce costs to patients by requiring a single copay, he said.
Side effects, including hyperemia, foreign body sensation, dryness, keratitis and pruritis, were not significantly different between the groups, according to Dr. Schuman.
“The combination drop had adverse events levels that were very similar to the concomitant use of the components,” he said. “The use of the combination drop did not seem to increase the number of adverse events.”
Mechanism of action
Extravan combines two drugs: a prostaglandin (travoprost) to increase aqueous drainage and a beta-blocker (timolol) to reduce aqueous production.
Dr. Schuman noted that there is potential for other glaucoma drug combinations to enter the market.
“There may be a better combination out there,” he said at the meeting. “On the other hand, this is significantly better than anything that’s currently available.”
A second of Alcon’s three phase 3 trials also compared Extravan to its components taken concomitantly. That study, which was presented here as a poster presentation, found that IOP was reduced to 18 mm Hg or lower in 91.2% of patients in the combination group, compared to 92% in the concomitant group.
Patients who used Extravan had diurnal pressure variations ranging from 0.3 mm Hg to 0.9 mm Hg. Among concomitant patients, mean diurnal pressure varied by 1.1 mm Hg to 1.3 mm Hg.
Extravan vs. travoprost
Another of the three studies, which was also presented as a poster here, compared Extravan solution to travoprost (0.004%) alone. Investigators found that Extravan lowered IOP by 2 mm Hg more than travoprost alone at the 8 a.m. time point. At 10 a.m. and 4 p.m., Extravan patients had pressures that were between 1 mm Hg and 2 mm Hg lower than the patients using travoprost alone.
Alcon has submitted a new drug application for Extravan solution to the U.S. FDA, and it has not yet been approved for marketing. Alcon plans to seek approval in other countries.
For Your Information:Reference:
- Joel S. Schuman, MD, is the Eye and Ear Foundation Professor and Chairman of Ophthalmology, University of Pittsburgh School of Medicine, and Director of UPMC Eye Center, 203 Lothrop St., Suite 816, Pittsburgh, PA 15213 U.S.A.; +1-412-647-2205; fax: +1-412-647-5119; e-mail: schumanjs@upmc.edu. Dr. Schuman receives grant and research support from Alcon.
- Choudhri S, Wand M, et al. A comparison of dorzolamide-timolol combination versus the concomitant drugs. Am J Ophthalmol. 2000;130:832-833.