Research Digest

Less Frequent Dosing of Ranibizumab Not as Effective

The first-year results of a phase 3b clinical trial of ranibizumab (Lucentis, Genentech), published by the American Journal of Ophthalmology, indicates that a less frequent fixed treatment regimen may not be optimal for the treatment of subfoveal choroidal neovascularization (CNV) secondary to AMD. One hundred eighty-four patients were included in the multicenter, double-masked study, which featured 2 dosings of ranibizumab (0.3 mg and 0.5 mg) and 1 of placebo. Sixty patients were randomized to the 0.3-mg group, 61 to the 0.5-mg group and 63 to sham.

The smaller phase 3b study was designed to investigate whether the drug would be as safe and efficacious when given at the same 2 doses as in the pivotal phase 3 ANCHOR and MARINA studies, but dosed less frequently. The investigators identified the primary efficacy endpoint as mean change from baseline visual acuity (VA) at month 12. Results showed the mean changes from baseline VA at 12 months were -16.3 letters for the sham group, -1.6 letters for the 0.3-mg group and -0.2 letters for the 0.5-mg group. And while ranibizumab halted CNV growth and reduced CNV-related leakage, the treatment effect declined under the quarterly dosing schedule ("at 3 months, the mean changes from baseline VA had been gains of 2.9 and 4.3 letters for the 0.3 mg and 0.5 mg doses, respectively," the authors say).

Carl D. Regillo, M.D., lead author of the paper, director of clinical retina research at Wills Eye Institute and professor of ophthalmology at Thomas Jefferson University, both in Philadelphia, reports that at the end of year 1, the mean VA of patients being treated with either of the doses was approximately the same as it was at baseline. "That's not quite as good, of course, as the pivotal phase 3 MARINA and ANCHOR studies because they showed, on average, a line or two of vision improvement by month 12," Dr. Regillo says. "So that was the first hint in the study that although ranibizumab was shown to be effective and safe as compared to the sham group, it wasn't as effective as monthly dosing. A few other endpoints were not as good as in the phase 3 studies. So it gave everyone the impression that patients may have been undertreated, on average, by treating quarterly."

He adds that clinicians should not extrapolate too much from this study, which will run for another year. Physicians must tailor their dosing regimen to the individual patient. "It's clear that some people need more than quarterly injections, but not necessarily everyone," Dr. Regillo explains. "In practice, we don't really ever give it on a fixed regimen, either monthly or every 3 months. You certainly can't treat patients in the same fashion to optimize results." OM

Gatifloxacin 1 Hour Preop vs. 1 Day

A recent study led by researchers at Stanford University School of Medicine compared the efficacy of topical gatifloxacin (Zymar, Allergan) in eliminating conjunctival bacterial flora following a 1-hour application with a 1-day application in patients about to undergo intraocular surgery. The study found the 1-hour prior-to-surgery application to be as effective as the 1-day application. Ninety-six eyes in 48 patients were evaluated in the masked non-randomized trial. Cultures were taken from the palpebral conjunctival sacs in both eyes at baseline. Researchers instructed patients to apply topical gatifoxacin into the surgical eye q.i.d. beginning 1 day before surgery (cataract, trabeculectomy or corneal transplant). On the surgical day, cultures were taken from both eyes with the surgical eye receiving gatifloxacin for 1 day and the contralateral eye receiving no treatment. One hour before surgery, both eyes received 3 more doses of the antibiotic, each given at 5-minute intervals. Investigators obtained cultures 45 minutes after the third doss. Thus, the surgical eye received 1-day and 1-hour gatifloxacin before surgery; the non-surgical eye received 1-hour antibiotic treatment.

For eyes that received preoperative antibiotic for 1 day and 1 hour, blood agar tests of the cultures showed that positive culture decreased from 56% at baseline to 13%. The nonsurgical eye that had received the 1-hour preop application showed a decrease from 63% at baseline to 13%. SeptiCheck (Becton Dickinson, Franklin Lakes, N.J.) tests of the cultures showed no statistical difference between the groups.

The study received support from Allergan. The abstract is on the Investigative Ophthalmology & Visual Science Web site at www.iovs.org. OM