Rescula first choice as adjunct therapy

The glaucoma drug’s safety profile makes it a good choice for adjunctive therapy, study shows.

LONDON — Rescula (unoprostone isopropyl, Novartis Ophthalmics) may be the first choice in combination therapy, according to three clinical trials.

Rescula in monotherapy was found to be as effective as betaxolol; however, it was found to be slightly less effective than timolol. Rescula combined with timolol is as effective as brimonidine plus timolol or dorzolamide plus timolol, said Jean-Philippe Nordmann, MD, PhD, of the Hôpital des Quinze-Vingts and professor of ophthalmology at University of Paris V in France.

He reported on three trials, Rescula as monotherapy, Rescula as adjunctive therapy and a systemic safety trial in a presentation at the European Glaucoma Society (EGS) meeting.

Efficacy and safety

The studies were undertaken to evaluate the efficacy and the safety of Rescula in monotherapy compared to beta-blockers and in combination with beta-blockers versus other combinations currently used in clinics, such as beta-blocker and dorzolamide, or beta-blocker and brimonidine. The last study in asthmatic patients was performed to ensure that Rescula is safe in this type of patient, as some doubts exist with Xalatan (latanoprost, Pharmacia), Dr. Nordmann told Ocular Surgery News.

The first study compared the intraocular pressure (IOP)-lowering efficacy and safety of unoprostone 0.15% as monotherapy to timolol maleate 0.5% and to betaxolol hydrochloride 0.5% twice daily. All subjects had primary open-angle glaucoma or ocular hypertension in this randomized, multicenter, active controlled, three-arm study that lasted 12 months. He presented the 6-month data at the EGS meeting.

Unoprostone twice daily was equal to betaxolol twice daily and slightly less effective than timolol twice daily, Dr. Nordmann said.

Rescula showed no peak trough effects and exhibited a consistent diurnal curve. No tachyphylaxis was observed after 6 months.

Age, gender, iris color, diagnosis, baseline IOP and prior beta-blocker therapy showed no differences between groups.

Side effects

In the monotherapy study, burning and stinging were the most commonly reported side effects for each arm. In the uno.prostone group, 50 patients (18%) reported stinging, while 16 (11.6%) timolol patients and 31 (22.1%) betaxolol patients reported it.

Burning and stinging upon instillation was reported separately and affected 19 (6.8%) unoprostone patients, four (2.9%) timolol patients and 18 (12.9%) betaxolol patients.

Other ocular adverse events included abnormal vision, conjunctivitis, corneal lesions, dry eyes, eyelid disorders, foreign body sensation, injection, itching and lacrimal disorders.

Non-ocular adverse events were similar for the three treatment groups, with headache and rhinitis most commonly reported.

“Rescula is very effective in monotherapy, even though slightly less than timolol,” Dr. Nordmann said. “In practice, the efficacy and safety profile of Rescula makes it a good choice in case of contraindication to beta-blockers.”

Adjunctive therapy

A second study measured unoprostone’s efficacy as an adjunctive therapy. The randomized, multicenter, active controlled, three-arm study compared unoprostone 0.15% plus timolol 0.5%, dorzolamide 2% plus timolol 0.5%, and brimonidine 0.5% plus timolol 0.5%.

All drugs were given twice daily, and treatment duration was 12 weeks. All patients had to have an IOP less than 22 mm Hg on beta-blocker therapy and on adjunctive therapy during enrollment, 2 weeks before the baseline day. Patients then started timolol 0.5% twice daily until the baseline day. They then started a double-masked adjunctive therapy treatment period, adding unoprostone, dorzolamide or bromonidine to the timolol for the next 12 weeks.

Efficacy as monotherapy IOP values at baseline and month 6

Efficacy as monotherapy 12-hour diurnal IOP at month 6

Researchers measured the change in mean 8-hour diurnal IOP at week 12. Equivalence was concluded if the upper limit of the 95% confidence interval around the difference between treatment means was lower than 1.5 mm Hg.

Adjunctive unoprostone patients had a mean IOP of 21.94 mm Hg at baseline and 19.21 mm Hg at week 12, a 2.73-mm Hg drop and a 12.28% change.

Adjunctive dorzolamide patients had a mean IOP of 21.68 mm Hg at baseline and 18.55 mm Hg at week 12, a 3.14-mm Hg drop and a 14.39% change.

Adjunctive brominidine patients had a mean of 21.13 mm Hg IOP at baseline and 18.37 mm Hg at week 12, a 2.77 mm Hg drop and a 12.52% change.

“Rescula is as effective as the other drugs currently used in combination,” Dr. Nordmann said. “As the safety profile of Rescula is better, one can consider that Rescula could be the best choice in combination. The combination with beta-blockers has been extensively studied, and it is likely that combination with other drugs, such as brinzolamide or dorzolamide, would work as well.”

Safety profile

An important advantage of Rescula is its safety profile, as almost no systemic side effect has been reported in the studies, Dr. Nordmann said.

Adverse events included clinical observations of changes in ocular symptoms, ophthalmoscopy findings, slit lamp findings, morning IOPs, visual acuity, visual field results, irides and abnormal eyelash growth.

“Rescula is better tolerated than timolol or betaxolol, for example. This has been proved in asthmatic patients,” Dr. Nordmann said. “Rescula has roughly the same local tolerance as beta-blockers. The only local side effect that I consider common is some discomfort at instillation that lasts a few seconds and disappears after 1 month or 2.”

Efficacy as monotherapy Responder analysis at month 6 ITT

Efficacy as adjunctive therapy Results: Mean 8 hour diurnal IOP (PP)

For Your Information:

• Jean-Philippe Nordmann, MD, can be reached at the Hôpital des Quinze-Vingts, Paris, France; (33) 1-40 02-12-00; fax: (33) 01-40-02-12-99. Ocular Surgery News could not confirm whether or not Dr. Nordmann has a direct financial interest in any of the products mentioned in this article or if he is a paid consultant for any companies mentioned.