Phase IV study shows improved DME outcomes with fluocinolone acetonide implant

By Lynda Charters;Reviewed by Jay G. Prensky, MD

An intravitreal fluocinolone acetonide implant (Iluvien, Alimera Sciences) provided patients with diabetic macular edema (DME) with anatomic and visual improvements at the 6-month evaluation in a phase IV study of the device’s efficacy, anatomic, and safety outcomes.

Patients with the worst baseline vision had the greatest improvements compared with those with better initial vision. The initial data suggested a decreased need for additional treatments for DME after implantation of the device

The PALADIN Real-World Observational Study is a prospective, non-randomized, open-label trial conducted to collect data from patients with DME who had been treated according to the U.S. indication to assess intraocular pressure (IOP) signals in this patient population.

Because the study dose of 0.2 mcg/day of fluocinolone acetonide is the only treatment for DME that continuously provides therapy for 3 years with 1 administration, the study will provide important information related to treatment burden, according to Jay Prensky, MD.

The 38-center study included 159 patients who were considered eligible for the implant based on the prescribing information. The best-corrected visual acuity (BCVA), central subfield thickness (CST), IOP, and lens status were recorded in 112 patients. Changes from the baseline BCVA and CST were analyzed at the 6-month evaluation. All patients had been treated for DME with steroids, anti-vascular endothelial growth factor (anti-VEGF) therapy, or laser.

Dr. Prensky, in private practice in Camp Hill, PA, reported the results of the interim analysis from 78 patients (51.3% male; mean age, 66.5 years) who completed the 6-month safety evaluation; 94 eyes were included in the safety assessment and 91 eyes in the visual assessment. The mean duration of DME was 5.3 years, mean BCVA 60.7 letters, mean CST 390.7 µm, and baseline IOP 14 mm Hg.

6-month findings

The investigators observed IOP elevations to over 30 mm Hg in 2 (2.1%) patients and an increase of 10 mm Hg or higher in 6 (6.4%) patients. No patients required surgery to control the IOP.

Thirteen (13.8%) patients were treated emergently with IOP-lowering medication, and 22 (23.4%) patients were treated with IOP-lowering medications, 9 of whom had been treated before undergoing implantation of the device. Cataracts developed in 4 (25%) of 16 phakic patients.

Importantly, the BCVA improved significantly (P < 0.002 at all time points) beginning as early as 7 days after the implant and the increase was sustained out to the 6-month time point, Dr. Prensky reported. Along with the improvements in the BCVA, concurrent decreases in the CST were seen early after implantation and remained decreased to the 6-month evaluation.

Significant decreases were seen after implantation at day 7 (P < 0.001), month 2 (P = 0.038), month 3 (P < 0.003), and month 6 (P < 0.001).

“At the 6-month examination, 57.5% of patients had a CST of 350 µm or less, and 39.1% had a CST of 300 µm or less,” Dr. Prensky said.

Regarding the BCVA, the patients who had worse vision at baseline had the biggest gains in visual acuity, with about 67% of patients with 20/40 or better at baseline maintaining vision without the need for additional DME treatments at month 6; 34.1% of patients received additional treatment for DME, with anti-VEGF therapy prescribed for most of those patients.

Looking to the future

Dr. Prensky explained that the plan for the patients who participated in the PALADIN study is to continue the follow-up for a minimum of 3 years and to collect DME treatment and IOP data for 3 years prior to the implantation of the device for comparison with the data collected after the device was implanted.

The current data will corroborate findings from the recent U.S. Retrospective Chart Review in Patients Receiving Iluvien clinical study (USER study), which assessed the real-world outcomes of the fluocinolone acetonide 0.2 mcg/day implant for DME at 4 U.S. study centers in 160 eyes of 130 patients, determine the anatomic and function responses before and after implantation of the device, compare the number of DME treatments before and after device implantation, and compare the IOP signals associated with the real-world data to those reported in the Fluocinolone Acetonide in Diabetic Macular Edema study.

“The fluocinolone acetonide 0.2 mcg/day implant was well tolerated,” Dr. Prensky concluded. “A small number of patients had an IOP that increased to over 30 mm Hg. IOP-lowering surgery was not required in any patient. The interim analysis of the ongoing PALADIN trial indicated that continuous micro-dosing with this implant led to early improvements in BCVA and CST that were stable for 6 months.

“Almost two-thirds of patients did not require additional therapies to treat DME,” Dr. Prensky added. “The increases in vision were associated with the baseline vision, with patients with better baseline vision achieving lower increases in the post-implantation vision. Future reports will assess the effects on treatment burden compared with before implantation of the device.

Jay G. Prensky, MD

e. jpensky@gmail.com

This article is based on a presentation Dr. Prensky delivered at the 2017 American Society of Retina Specialists meeting. Dr. Prensky is an investigator for Alimera Sciences, which supported the study.