Glenn J Jaffe1, Carlos E Pavesio2. 1. Department of Ophthalmology, Duke University Eye Center, Duke University, Durham, North Carolina. Electronic address: jaffe001@mc.duke.edu. 2. Moorfields Eye Hospital, London, United Kingdom.
Abstract
PURPOSE: To examine the 36-month efficacy and safety of a 0.2 μg/day fluocinolone acetonide insert (FAi) to treat noninfectious uveitis of the posterior segment (NIU-PS). DESIGN: Phase 3, prospective, double-masked, multicenter study (clinicaltrials.gov, NCT01694186). PARTICIPANTS: Adults (≥18 years old) with a diagnosis of NIU-PS in ≥1 eye for ≥1 year and ≥2 recurrences of uveitis requiring systemic corticosteroid, immunosuppressive treatment, or intraocular corticosteroids. METHODS: Participants were randomized 2:1 to FAi or sham (injection plus standard of care) treatment. MAIN OUTCOME MEASURES: The primary outcome was the difference between the proportion of FAi-treated and sham-treated patients who had a uveitis recurrence. Secondary outcomes included time to first recurrence, number of recurrences, best-corrected visual acuity (BCVA) change from baseline, resolution of macular edema, and number of adjunctive treatments. RESULTS:One hundred twenty-nine participants (n = 87 FAi-treated; n = 42 sham-treated) were enrolled. Over 36 months of treatment, cumulative uveitis recurrences were significantly reduced with FAi compared with sham (65.5% vs. 97.6%, respectively; P < 0.001); time to first recurrence was commensurately longer (median 657.0 and 70.5 days, respectively; P < 0.001). The number of recurrences per eye was significantly lower in the FAi-treated compared with the sham-treated group (mean 1.7 vs. 5.3, respectively, P < 0.001). At 36 months, more FAi-treated eyes had a ≥15-letter increase in BCVA from baseline and fewer FAi-treated eyes had investigator-determined macular edema at month 36 compared with sham-treated eyes (33.3% vs. 14.7% and 13.0% vs. 27.3% for BCVA and macular edema, respectively). Fewer FAi compared with sham-treated participants required adjunctive treatments (57.5% vs. 97.6%, respectively). Intraocular pressure (IOP) was similar for both study groups at month 36 (mean ± standard deviation 14.5±5.1 and 14.8±5.3, respectively), and approximately half as many eyes in the FAi-treated group when compared with the sham-treated group underwent IOP-lowering surgery (5.7% vs. 11.9%). Cataract surgery was required more frequently over 36 months in the FAi-treated compared with the sham-treated group (73.8% vs. 23.8% of eyes, respectively). CONCLUSIONS:Fluocinolone acetonide insert-treated eyes had significantly reduced uveitis recurrence rates throughout the study duration, significantly increased recurrence-free durations, fewer recurrence episodes among those with recurrences, less adjunctive therapy, and an acceptable side-effect profile compared with sham-treated eyes.
RCT Entities:
PURPOSE: To examine the 36-month efficacy and safety of a 0.2 μg/day fluocinolone acetonide insert (FAi) to treat noninfectious uveitis of the posterior segment (NIU-PS). DESIGN: Phase 3, prospective, double-masked, multicenter study (clinicaltrials.gov, NCT01694186). PARTICIPANTS: Adults (≥18 years old) with a diagnosis of NIU-PS in ≥1 eye for ≥1 year and ≥2 recurrences of uveitis requiring systemic corticosteroid, immunosuppressive treatment, or intraocular corticosteroids. METHODS:Participants were randomized 2:1 to FAi or sham (injection plus standard of care) treatment. MAIN OUTCOME MEASURES: The primary outcome was the difference between the proportion of FAi-treated and sham-treated patients who had a uveitis recurrence. Secondary outcomes included time to first recurrence, number of recurrences, best-corrected visual acuity (BCVA) change from baseline, resolution of macular edema, and number of adjunctive treatments. RESULTS: One hundred twenty-nine participants (n = 87 FAi-treated; n = 42 sham-treated) were enrolled. Over 36 months of treatment, cumulative uveitis recurrences were significantly reduced with FAi compared with sham (65.5% vs. 97.6%, respectively; P < 0.001); time to first recurrence was commensurately longer (median 657.0 and 70.5 days, respectively; P < 0.001). The number of recurrences per eye was significantly lower in the FAi-treated compared with the sham-treated group (mean 1.7 vs. 5.3, respectively, P < 0.001). At 36 months, more FAi-treated eyes had a ≥15-letter increase in BCVA from baseline and fewer FAi-treated eyes had investigator-determined macular edema at month 36 compared with sham-treated eyes (33.3% vs. 14.7% and 13.0% vs. 27.3% for BCVA and macular edema, respectively). Fewer FAi compared with sham-treated participants required adjunctive treatments (57.5% vs. 97.6%, respectively). Intraocular pressure (IOP) was similar for both study groups at month 36 (mean ± standard deviation 14.5±5.1 and 14.8±5.3, respectively), and approximately half as many eyes in the FAi-treated group when compared with the sham-treated group underwent IOP-lowering surgery (5.7% vs. 11.9%). Cataract surgery was required more frequently over 36 months in the FAi-treated compared with the sham-treated group (73.8% vs. 23.8% of eyes, respectively). CONCLUSIONS:Fluocinolone acetonide insert-treated eyes had significantly reduced uveitis recurrence rates throughout the study duration, significantly increased recurrence-free durations, fewer recurrence episodes among those with recurrences, less adjunctive therapy, and an acceptable side-effect profile compared with sham-treated eyes.
Authors: Faruque Ghanchi; Rupert Bourne; Susan M Downes; Richard Gale; Christina Rennie; Ian Tapply; Sobha Sivaprasad Journal: Eye (Lond) Date: 2022-01-01 Impact factor: 4.456
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