Latanoprost a safe and effective alternative 

By Cheryl Guttman

Fort Lauderdale — Latanoprost (Xalatan) offers a safe and effective alternative when other agents are not producing adequate IOP reductions, according to two large prospective multicentre studies.

The Assessing Xalatan in Switch (AXIS) study is an open-label trial of patients whose physician deemed a therapeutic change was indicated because of insufficient IOP control, adverse event, noncompliance or suspected noncompliance.
Thom J Zimmerman MD, PhD presented six-week follow-up data from 888 patients who were enrolled in that study at the annual meeting of the Association for Research in Vision and Ophthalmology.

All patients had received at least one week of previous monotherapy. Patients had taken any of 17 different drugs and all classes of glaucoma medications, including other prostaglandin-like agents.
Almost 93% of enrolled subjects reached the six-week follow-up visit. The mean reduction from baseline IOP in those individuals was
3.0 mm Hg, he reported.

“The results of this study provide clinicians with the security of knowing that they can change treatment to latanoprost from any monotherapy regimen with reasonable assurance that the patient will likely tolerate their new treatment and benefit with maintenance or a decrease in IOP,” explained Dr Zimmerman, Senior Medical Director at Pharmacia and Emeritus Professor and Chairman of Ophthalmology, University of Louisville, Kentucky.

The AXIS study is ongoing. Approximately 3,000 patients are now participating and will be followed for six months after being switched from existing monotherapy to latanoprost.

Of the 888 patients included in the initial interim analysis presented by Dr Zimmerman, almost 90% were being treated for primary open angle glaucoma. The rest were ocular hypertension patients.
Reasons for medication change included was lack of efficacy in 599 patients (67.5%) and adverse event in 139 (15.7%). Noncompliance issues with existing therapy was the underlying cause for the enrolment of the remaining patients.

Switching drugs a useful strategy
Some 83% of the patients who were switched to latanoprost because of lack of efficacy of previous treatment achieved an IOP reduction of at least 1.0 mm Hg. Two out of three patients enrolled due to noncompliance with existing medication achieved similar reductions.
A full 90% of the 139 patients whose therapy was changed to latanoprost because of safety issues maintained IOP control while experiencing resolution of their previous treatment-induced adverse event.

When patients were stratified by their previous therapy, the six-week analyses showed IOP reductions from baseline were achieved consistently across all 17 groups. For most groups, the difference between the mean six-week and baseline IOP values was approximately 3 mm Hg. The benefit of latanoprost treatment for further reducing IOP was statistically significant in 11 of the 17 groups.

Two groups where statistical significance was not achieved were represented by patients switched to latanoprost from bimatoprost or travoprost. Mean baseline IOP values for those two groups were already among the lowest recorded in the study. IOP control for those patients was at least maintained after switching to latanoprost, Dr Zimmerman said.

Of the 63 patients who withdrew prior to the six-week visit, 27 (3%) patients stopped latanoprost because of an adverse event and 24 (2.7%) withdrew because of inadequate IOP response to treatment. Adverse events causing withdrawal from the study included conjunctival hyperemia (8%), body pain (4%) and ocular burning/stinging (5%).

Latanoprost-Brimonidine study group
Carl B Camras MD, Professor and Chairman of Ophthalmology, University of Nebraska, presented another study — the six-month US Latanoprost-Brimonidine Study Group trial which included 301 patients.
The study showed that latanoprost was significantly more effective than brimonidine in controlling IOP and offered a much more favorable safety profile, Dr Camras observed.
“The findings of this trial strongly corroborate previous head-to-head comparison studies that have shown latanaprost a significantly more effective ocular hypotensive agent than brimonidine when IOP is assessed on a diurnal basis. The study also confirms that latanoprost is better tolerated.”
Patients enrolled in the Latanoprost-Brimonidine study had to be at least 18 years of age with a diagnosis of primary open-angle glaucoma or ocular hypertension and an IOP of 22 mm Hg or higher without medication.
Both previously untreated individuals and those receiving monotherapy were eligible to participate. Any existing medical treatment for glaucoma was washed out prior to measurement of baseline IOP.

Treatment assignment was based on a 1:1 randomisation scheme and the evaluators were masked to study medication. Latanoprost was administered once daily at 8 a.m. and brimonidine was given twice a day at 8 a.m. and 8 p.m. Diurnal IOP was calculated as the average of measurements obtained at 8 a.m.,
10 a.m., 12 p.m. and 4 p.m. at the baseline, third and six month visits.

Baseline diurnal IOP values were 24.6 mm Hg in the latanoprost group and 24.8 mm Hg among brimonidine-treated patients. At three months, diurnal IOP was reduced significantly more from baseline in patients receiving latanoprost compared to brimonidine.

That benefit was maintained at six months, when adjusted mean diurnal IOP reductions were 5.7 mm Hg for latanoprost and 3.1 mm Hg for brimonidine.

The mean percentage reduction in diurnal IOP was 23% for latanoprost and 13% for brimonidine. Among latanoprost-treated patients, 44% achieved a 25% or greater reduction in diurnal IOP. That proportion was more than three times higher than the 13% rate observed in the brimonidine group.

The IOP-lowering effects of the two medications were not significantly different at 10 a.m. and 12 p.m. However, comparisons of IOP reductions obtained at 8 a.m. and 4 p.m. showed statistically significant differences favouring the greater efficacy of latanoprost.
At the first measurement in the morning, mean IOP was 2.9 mm Hg lower in the latanoprost group compared to the brimonidine-treated patients, and at 4 p.m. the difference in IOP-lowering effect between treatments was 3.9 mm Hg.

Local ocular reactions
Adverse events caused seven (5%) latanoprost-treated patients and 26 (17%) brimonidine-treated patients to discontinue study participation. Those side effects consisted of local ocular reactions in two latanoprost patients and 18 brimonidine patients.

Five patients receiving brimonidine withdrew because of central nervous system-related adverse events, including fatigue, dizziness, somnolence, depression, mental impairment and headache. None of the adverse event-related withdrawals in the latanoprost were associated with central nervous system sequelae.

Dr Camras is a consultant to the Pharmacia Corporation.



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