Findings of a recent study show that loteprednol 0.5%/tobramycin 0.3% and dexamethasone 0.1%/tobramycin 0.3% were equivalent in reducing the signs and symptoms of blepharokeratoconjunctivitis. Some safety concerns emerged, however, concerning elevated IOP in patients treated with the dexamethasone/tobramycin product.
Los Angeles-In a comparison study of safety and efficacy, two combination agents were equally effective in reducing the signs and symptoms of ocular inflammation associated with blepharokeratoconjunctivitis. Jonathan Macy, MD, a private practitioner in Los Angeles, and colleagues recently published the evaluation of loteprednol 0.5%/tobramycin 0.3% (Zylet, Bausch & Lomb) with dexamethasone 0.1%/tobramycin 0.3% (Tobradex, Alcon Laboratories).
The multicenter, randomized, investigator-masked, parallel group study evaluated a newer combination agent, loteprednol/tobramycin, and an established product generally considered the standard therapy, dexamethasone/tobramycin. Loteprednol/tobramycin received FDA approval in December 2004, and dexamethasone/tobramycin was approved in November 1988. Although other combination drugs have been introduced, none has approached dexamethasone/tobramycin in popularity because of the broad spectrum of coverage provided by the tobramycin and the potent, well-tolerated steroid component, dexamethasone, Dr. Macy said.
The study appeared recently was published (Curr Med Res Opin. 2008; 24:287-296). Its objective was not to demonstrate whether one agent was better than the other but to demonstrate non-inferiority.
He explained that patients treated with dexamethasone/tobramycin had a statistically significant increase in IOP compared with those treated with loteprednol/tobramycin at day 7, day 15, and overall. Twice as many patients in the dexamethasone/tobramycin treatment group experienced increases in IOP of 5 to 9 mm/Hg above baseline, and one individual in the dexamethasone/tobramycin group had an increase of at least 10 mm Hg over baseline.
The study was conducted at 17 centers in the United States; between January and June 2007, 276 patients with blepharokeratoconjunctivitis were randomly assigned to receive loteprednol/tobramycin (n = 138) or dexamethasone/tobramycin (n = 138). Of these, 263 completed the study (132, loteprednol/tobramycin, and 131, dexamethasone/tobramycin). Baseline characteristics of the two treatment groups were similar. The mean age in both was 55 years, and the majority was white.
After randomization, patients were to self-administer 1 or 2 drops of medication in the affected eye at approximately 4-hour intervals during the day for 14 days. Follow-up visits were scheduled at days 1, 3, 7, and 15.
The efficacy assessment was based on ocular signs and symptoms as well as the investigator's global assessment. Ocular signs assessed were blepharitis, conjunctivitis, and keratitis, and the symptoms included were itchiness, foreign body sensation, blurred vision, light sensitivity, painful or sore eyes, and burning. The global assessment was performed by rating overall global changes on a 4-point scale from 0 (cured) to 3 (worsened), relative to the previous visit.
The safety endpoints were visual acuity, biomicroscopy findings, IOP measurements, and adverse events; they were assessed at each visit.
The results showed that mean days on the study were 14.6 and 14.5 for the loteprednol/tobramycin and dexamethasone/tobramycin groups, respectively, and the mean number of drops per eye per day was 5.70 and 5.71, respectively. Both groups had a decline of 78% from baseline in their signs and symptoms, based on composite scores from all study visits. The percentage of patients considered cured at the final visit was 43.6% for the loteprednol/tobramycin group and 40.9% for the dexamethasone/tobramycin group.
Four subjects in each treatment group reported a non-ocular treatment-emergent adverse event (AE). Most were considered mild to moderate except for one case of hypertension in the dexamethasone/tobramycin group and one instance of headache in the loteprednol/tobramycin group, which were classified as severe. In addition, four subjects in the loteprednol/tobramycin group and nine in the dexamethasone/tobramycin group reported ocular adverse events. AEs in the loteprednol/tobramycin group included allergic conjunctivitis, eye irritation, eye pain, and increased IOP, and events in the dexamethasone/tobramycin group included decreased lacrimation, punctate keratitis, foreign body sensation, and increased IOP. All were considered mild to moderate in severity.