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A single sustained-release dexamethasone intravitreal implant resulted in resolution of inflammation and improvement in visual acuity (VA) in patients with intermediate or posterior uveitis through 26 weeks in a multicenter, randomized, controlled clinical trial.
The device, a bioerodable PLA/PLGA implant containing one of two doses of dexamethasone, was more efficacious at the 700-μg dose compared with the 350-μg dose or sham treatment. The safety profile was good, with mild increases in IOP that resolved over time.
Dr. Whitcup reported the results of a phase III trial for the Uveitis Study Group during retina subspecialty day at the annual meeting of the American Academy of Ophthalmology.
A new treatment approach is the bioerodable drug delivery system containing dexamethasone. The PLA and PLGA implants degrade into lactic acid, glycolic acid, water, and carbon dioxide and release dexamethasone into the eye, Dr. Whitcup said.
The preclinical pharmacokinetic studies indicated that extremely high doses of dexamethasone are present in the eye initially.
"About 1,000-fold higher levels of dexamethasone are present in the eye compared with triamcinolone," he said. "Almost immediately after implantation of the device, the drug is released in a sustained-release fashion [for] about 6 months."
The trial was a 26-week, multi-masked, randomized, sham-controlled study of a dexamethasone intravitreal implant to treat noninfectious intermediate or posterior uveitis. The use of the implant for uveitis is an off-label use of this drug.
The 229 patients were randomly assigned to receive one of two doses of dexamethasone, 700 μg (77 patients) or 350 μg (76 patients), or to sham treatment (76 patients). Most patients completed the study, 94.8%, 96.1%, and 93.4%, respectively.
To participate in the study, patients had to be aged 18 or more years with noninfectious intermediate or posterior uveitis, have greater than +1 vitreous haze on a scale of 0 to 4, and have a best-corrected visual acuity (BCVA) of 20/32 to 20/630. Patients with a history of glaucoma or those who used an IOP-lowering medication within a month of enrollment in the study were excluded.
The primary study endpoint was the number of patients with grade 0 vitreous haze at week 8 after the start of treatment. Other key study points were the status of the vitreous haze at week 26 of the study, the BCVA, adverse events, and IOP measurement.
Most patients had intermediate uveitis and had vitreous haze of greater than 2+.
"At week 6 of treatment, there was a significant (p <0.001) difference between the active treatment groups and the sham group in the level of vitreous haze," Dr. Whitcup said. "The difference persisted to week 26."
The active treatment groups also had a three-line increase in VA that started at week 3 of treatment and lasted for the 26 weeks of the study.
"Significantly (p <0.001) more patients treated with both doses of dexamethasone implants achieved the three-line increase compared with the sham group," he said. "The efficacy was greater at the later time points, especially in the 700-μg group compared with 350 μg."
The change in mean VA in the two treatment groups was similar; there was a mean improvement of about 14 letters in the higher-dose group and about 13 letters in the lower-dose group, Dr. Whitcup said.
The patients assigned to the active treatment groups also had improvement in their quality of life measure on the National Eye Institute-Visual Function Questionnaire (NEI-VFQ) 25.
"Treatment with 700 μg of dexamethasone resulted in significant (p = 0.004) and clinically meaningful improvements at 6 months in the NEI-VFQ compared with sham," he said.
The most frequently occurring adverse event was increased IOP in the treatment groups compared with the sham group. One case of culture-negative endophthalmitis developed in the 700-μg group. No differences were seen among the groups in the number of cataract surgeries and retinal detachments, and no glaucoma surgeries were needed, although one patient in the 350-μg group required a laser iridotomy for a narrow angle. IOP increases were mild among the groups.
More patients in the sham group required escape medications to treat uveitis than in the active treatment groups at any visit.
By week 3, 15% of patients in the sham group needed an escape medication compared with 1% and 3% in the high- and low-dose treatment groups, respectively, Dr. Whitcup said.
"One injection of the dexamethasone implant was significantly more effective than sham in eliminating vitreous haze through week 26 of the study," he said. "At the primary endpoint, about four-fold more patients treated with 700 μg of dexamethasone had complete resolution of vitreous haze compared with those treated with sham. Improvement in the BCVA with dexamethasone was sustained until week 26. Treatment also resulted in significant improvements in the quality of life on the NEI-VFQ 25.
"Overall, the efficacy with the 700-μg dose was greater compared with the 350-μg dose, with a similar safety profile," he concluded.