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Uveitis recurrence rate lowered, adjunctive therapy reduced with implant
Retisert slowly releases fluocinolone acetonide during a 3-year period. The implant was effective in patients with chronic noninfectious posterior uveitis. It recently received FDA approval.
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FORT LAUDERDALE, Fla. — Patients who received a sustained-release fluocinolone acetonide implant had a significantly lower rate of uveitis after implantation than in the year before implantation, according to Glenn J. Jaffe, MD. The need for adjunctive therapy was also reduced in treated eyes, he said.
Dr. Jaffe presented results of a 2-year phase 2b/3 study of the device here at the Association for Research in Vision and Ophthalmology (ARVO) meeting. Retisert (fluocinolone acetonide intravitreal implant, Bausch & Lomb) is an extended-release implant, designed to deliver the corticosteroid fluocinolone acetonide to the back of the eye over a period of approximately 2.5 years. The device was approved for treatment of chronic, noninfectious posterior segment uveitis by the Food and Drug Administration in April. It was given orphan drug designation for the indication.
“There was a low rate of recurrence of uveitis,” Dr. Jaffe said during a press briefing at the ARVO meeting. “The use of systemic steroids, immunosuppressant or periocular injections was also reduced significantly in patients implanted with the device.”
In the study, 278 patients with uveitis were randomized to implantation in one eye with either a 0.59-mg or 2.1-mg formulation of Retisert. The uveitis recurrence rate before implantation in the treated eye and the rate in the untreated fellow eye were used as controls.
The recurrence rate in treated eyes declined from 59.7% before implantation to 5.4% after implantation at 1 year postoperative. By 2 years, the eyes implanted with the Retisert device had a recurrence rate of 11.2%, compared with a more than 50% recurrence rate in the untreated fellow eyes. This difference was statistically significant, Dr. Jaffe said.
“The recurrence rate dropped dramatically in the study eye, whereas in the fellow eye it actually increased significantly from 25.4% at baseline,” he noted.
By 2 years postoperatively, the need for adjunctive therapy with steroids or immunosuppressants in the study eyes decreased from 52.5% to 12.5%, and the need for periocular injection of steroids dropped from 68% to 9.7%, Dr. Jaffe said. In the fellow eyes, the need for adjunctive therapy increased from 30.4% prior to study enrollment to 45.3% after study enrollment.
The Retisert implant is expected to be available to practitioners this summer, according to Bausch & Lomb.
Reason for fluocinolone
In the multicenter trial for FDA approval, two formulations of the Retisert device were evaluated. Each released fluocinolone acetonide at a different level, Dr. Jaffe said. The formulation that was approved releases the drug at a steady rate of 0.3 to 0.4 µg daily. The implant contains 0.59 mg of the active ingredient.
“The point about the different release rates is that the one that releases more quickly would theoretically produce higher levels [of the drug] in the eye compared to the one that didn’t release as quickly. The two different release rates provided two different dosages to test in clinical trials,” he told OSN.
In previous trials during the development of the sustained-release Retisert device, another corticosteroid, dexamethasone, was tested, but it did not last as long as the fluocinolone acetonide, Dr. Jaffe said.
“The idea behind the fluocinolone acetonide was that it would last longer because it didn’t dissolve well in an aqueous solution. The low solubility meant that it would be there in relatively low concentrations, but it would be released very slowly,” he said.
Patient criteria and safety
Patients with chronic noninfectious posterior uveitis for more than 1 year were eligible for the trial. Cataract and elevated IOP levels are common in patients with uveitis, and the drug released may accelerate the two conditions. Patients with cataract were not enrolled to allow better vision evaluation. To be eligible for enrollment, patients had to have IOP levels less than 25 mm Hg on no more than two pressure-lowering medications, Dr. Jaffe said. As the study progressed, several patients developed cataract or required filtering surgery.
In addition to elevated IOP and cataract development, investigators observed patients for endophthalmitis, bleeding, retinal detachment, choroidal detachment and improper positioning of the implant. A small percentage of patients developed retinal detachment, but the rate was consistent with previous studies of patients with uveitis who did not undergo Retisert placement, Dr. Jaffe said.
“In general, [this complication] is higher in patients with uveitis than in the general population,” he said.
VA from baseline
Mean pre-trial visual acuity for study eyes in the multicenter FDA trial was 20/250. Visual acuity was unequal between the two eyes immediately following implantation, Dr. Jaffe said. By 6 months, however, the eyes with the implant had improved to 20/125, comparable to the fellow eyes, he said.
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Significant improvement in visual acuity was noted in the trial, although it generally declines in this population, Dr. Jaffe said. Even if macular edema is relieved in patients with posterior uveitis, there has often already been irreversible damage to the retina, he said.
“The majority of the eyes either had stabilized or improved vision during the study period,” he said.
According to Bausch & Lomb, 24% of the patients gained three lines of vision or more.
There is little data to date as to how many patients maintain quiet eyes after the drug reservoir in the implant is depleted, Dr. Jaffe said. Ideally, the duration of the device would sufficiently suppress inflammation and reduce the rate of recurrence. He recommended monitoring patients for flare-ups and replacing the device only if there is a recurrence.
“I’ve seen some patients go up to 5 years without a flare-up. I’ve also seen a handful of patients who had flare-ups between 2 and 3 years. I’ve replaced the device, and the eyes have gotten quiet again. I would decrease the intervals between visits so that I could monitor them for flare-ups, but I wouldn’t routinely [re-]implant them,” he said.
Future trials
The fluocinolone acetonide device continues to be investigated for other indications, Dr. Jaffe said. The Multicenter Uveitis Steroid Treatment (MUST) trial in the United States is comparing the implant to intravitreal injection of steroids. Patients who do not tolerate steroid treatment will be treated with immunosuppressants and will be compared to patients who receive the implant, he said.
“The idea is to [assess] the relative benefits and risks of those two different types of treatment,” he said.
A similar trial is being conducted in Europe, he said.
Dr. Jaffe is also conducting a compassionate-use trial to evaluate the Retisert implant for the treatment of central and branch retinal vein occlusion.
“It’s specific for macular edema associated with those two conditions,” he said.
Other investigators are evaluating the implant for the treatment of diabetic macular edema, he said.
For Your Information:Reference:
- Glenn J. Jaffe, MD, can be reacha paid consultant for Bausch & Lomb. He has no direct financial interest in the products mentioned in this article.ed at Box 382, Duke University Eye Center, Durham, NC 27710; 919-684-4458; fax: 919-684-6474. Dr. Jaffe has received research support from Control Delivery Systems Inc.
- Jaffe GJ, McCallum RM, et al. Long-term follow-up results of a pilot trial of a fluocinolone acetonide implant to treat posterior uveitis. Ophthalmology. 2005;112:1192-1198.
- Jeanne Michelle Gonzalez is an OSN Staff Writer who covers all aspects of ophthalmology, specializing in practice management, regulatory and legislative issues. She focuses geographically on Latin America.