Dataset Information

Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial.

ABSTRACT:

Objective

To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious intermediate, posterior, or panuveitis (uveitis).

Design

Randomized controlled parallel superiority trial.

Participants

Patients with active or recently active uveitis.

Methods

Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (3 countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis.

Main outcome measures

Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life, ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked.

Results

On evaluation of changes from baseline to 24 months among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), the implant and systemic therapy groups had an improvement in visual acuity of +6.0 and +3.2 letters (P = 0.16, 95% confidence interval on difference in improvement between groups, -1.2 to +6.7 letters, positive values favoring implant), an improvement in vision-related quality of life of +11.4 and +6.8 units (P = 0.043), a change in EuroQol-EQ5D health utility of +0.02 and -0.02 (P = 0.060), and residual active uveitis in 12% and 29% (P=0.001), respectively. Over the 24 month period, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio [HR] = 3.3, P < 0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, P < 0.0001), and glaucoma (17%, HR=4.2, P = 0.0008). Patients assigned to systemic therapy had more prescription-requiring infections than patients assigned to implant therapy (0.60 vs 0.36/person-year, P=0.034), without notable long-term consequences; systemic adverse outcomes otherwise were unusual in both groups, with minimal differences between groups.

Conclusions

In each treatment group, mean visual acuity improved over 24 months, with neither approach superior to a degree detectable with the study's power. Therefore, the specific advantages and disadvantages identified should dictate selection between the alternative treatments in consideration of individual patients' particular circumstances. Systemic therapy with aggressive use of corticosteroid-sparing immunosuppression was well tolerated, suggesting that this approach is reasonably safe for local and systemic inflammatory disorders.

Financial disclosure(s)

Proprietary or commercial disclosure may be found after the references.

SUBMITTER: Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group

PROVIDER: S-EPMC3191365 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Publications

Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial.

Kempen John H JH Altaweel Michael M MM Holbrook Janet T JT Jabs Douglas A DA Louis Thomas A TA Sugar Elizabeth A EA Thorne Jennifer E JE

Ophthalmology 20110815 10

<h4>Objective</h4>To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious intermediate, posterior, or panuveitis (uveitis).<h4>Design</h4>Randomized controlled parallel superiority trial.<h4>Participants</h4>Patients with active or recently active uveitis.<h4>Methods</h4>Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 2 ...[more]

PMID: 21840602

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Project description:To evaluate the 3-year incremental cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for the treatment of noninfectious intermediate, posterior, and panuveitis.Randomized, controlled, clinical trial.Patients with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment Trial.Data on cost and health utility during 3 years after randomization were evaluated at 6-month intervals. Analyses were stratified by disease laterality at randomization (31 unilateral vs 224 bilateral) because of the large upfront cost of the implant.The primary outcome was the incremental cost-effectiveness ratio (ICER) over 3 years: the ratio of the difference in cost (in United States dollars) to the difference in quality-adjusted life-years (QALYs). Costs of medications, surgeries, hospitalizations, and regular procedures (e.g., laboratory monitoring for systemic therapy) were included. We computed QALYs as a weighted average of EQ-5D scores over 3 years of follow-up.The ICER at 3 years was $297,800/QALY for bilateral disease, driven by the high cost of implant therapy (difference implant - systemic [?]: $16,900; P < 0.001) and the modest gains in QALYs (? = 0.057; P = 0.22). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.003 and 0.04, respectively. The ICER for unilateral disease was more favorable, namely, $41,200/QALY at 3 years, because of a smaller difference in cost between the 2 therapies (? = $5300; P = 0.44) and a larger benefit in QALYs with the implant (? = 0.130; P = 0.12). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.53 and 0.74, respectively.Fluocinolone acetonide implant therapy was reasonably cost-effective compared with systemic therapy for individuals with unilateral intermediate, posterior, or panuveitis but not for those with bilateral disease. These results do not apply to the use of implant therapy when systemic therapy has failed or is contraindicated. Should the duration of implant effect prove to be substantially >3 years or should large changes in therapy pricing occur, the cost-effectiveness of implant versus systemic therapy would need to be reevaluated.

Project description:PurposeTo compare the benefits of fluocinolone acetonide implant therapy versus systemic corticosteroid therapy supplemented (when indicated) with immunosuppression for intermediate uveitis, posterior uveitis, and panuveitis.DesignAdditional follow-up of a randomized comparative effectiveness trial cohort.ParticipantsTwo hundred fifty-five patients with intermediate uveitis, posterior uveitis, or panuveitis randomized to implant or systemic therapy.Main outcome measuresBest-corrected visual acuity (BCVA), visual field mean deviation (MD), activity of uveitis, and presence of macular edema (per reading center grading) ascertained prospectively.MethodsTrial participants were followed-up for 54 months from original randomization.ResultsThe visual function trajectory in uveitic eyes demonstrated a similar (P = 0.73) degree of modest (not statistically significant) improvement from baseline to 54 months in both groups (mean improvement in BCVA at 54 months, 2.4 and 3.1 letters in the implant and systemic groups, respectively). Many had excellent initial visual acuity, limiting the potential for improvement. The mean automated perimetry MD score remained similar to baseline throughout 48 months of follow-up in both groups. Overall control of inflammation was superior in the implant group at every time point assessed (P < 0.016), although most eyes in the systemic therapy arm also showed substantial improvement, achieving complete control or low levels of inflammation. Although macular edema improved significantly more often with implant treatment within the first 6 months, the systemic group gradually improved over time such that the proportions with macular edema converged in the 2 groups by 36 months and overlapped thereafter (P = 0.41 at 48 months).ConclusionsVisual outcomes of fluocinolone acetonide implant and systemic treatment for intermediate uveitis, posterior uveitis, and panuveitis were similarly favorable through 54 months. The implant maintained a clear advantage in controlling inflammation through 54 months. Nevertheless, with systemic therapy, most patients also experienced greatly improved inflammatory status. Macular edema improved equally with longer follow-up. Based on cost effectiveness and side-effect considerations, systemic therapy may be indicated as the initial treatment for many bilateral uveitis cases. However, implant therapy is a reasonable alternative, especially for unilateral cases and when systemic therapy is not feasible or is not successful.

Project description:PURPOSE:To evaluate the risks and quality-of-life (QoL) outcomes of fluocinolone acetonide implant versus systemic therapy with corticosteroid and immunosuppression when indicated for intermediate uveitis, posterior uveitis, and panuveitis. DESIGN:Additional follow-up of a randomized trial cohort. PARTICIPANTS:Two hundred fifty-five patients with intermediate uveitis, posterior uveitis, or panuveitis, randomized to implant or systemic therapy. METHODS:Randomized subjects with intermediate uveitis, posterior uveitis, or panuveitis (479 eyes) were followed up over 54 months, with 79.2% completing the 54-month visit. MAIN OUTCOME MEASURES:Local and systemic potential complications of the therapies and self-reported health utility and vision-related and generic health-related QoL were studied prospectively. RESULTS:Among initially phakic eyes, cataract and cataract surgery occurred significantly more often in the implant group (hazard ratio [HR], 3.0; P = 0.0001; and HR, 3.8; P < 0.0001, respectively). In the implant group, most cataract surgery occurred within the first 2 years. Intraocular pressure elevation measures occurred more frequently in the implant group (HR range, 3.7-5.6; all P < 0.0001), and glaucoma (assessed annually) also occurred more frequently (26.3% vs. 10.2% by 48 months; HR, 3.0; P = 0.0002). In contrast, potential complications of systemic therapy, including measures of hypertension, hyperlipidemia, diabetes, bone disease, and hematologic and serum chemistry indicators of immunosuppression toxicity, did not differ between groups through 54 months. Indices of QoL initially favored implant therapy by a modest margin. However, all summary measures of health utility and vision-related or generic health-related QoL were minimally and nonsignificantly different by 54 months, with the exception of the 36-item Short-Form Health Survey physical component summary score, which favored implant by a small margin at 54 months (3.17 on a scale of 100; P = 0.01, not adjusted for multiple comparisons). Mean QoL results were favorable in both groups. CONCLUSIONS:These results suggest that fluocinolone acetonide implant therapy is associated with a clinically important increased risk of glaucoma and cataract with respect to systemic therapy, suggesting that careful monitoring and early intervention to prevent glaucoma is warranted with implant therapy. Systemic therapy subjects avoided a significant excess of toxicities of systemic corticosteroid and immunosuppressive therapies in the trial. Self-reported QoL measures initially favored implant therapy, but over time the measures converged, with generally favorable QoL in both groups.

Project description:ImportanceA randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known.ObjectiveTo compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis.Design, setting, and participantsNonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016).InterventionsParticipants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated.Main outcomes and measuresPrimary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death.ResultsSeven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%).Conclusions and relevanceIn 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up.Trial registrationclinicaltrials.gov Identifier: NCT00132691.

Project description:ObjectiveTo examine the long-term efficacy and safety of the intravitreal 0.2-μg/day fluocinolone acetonide implant (FAi) to treat noninfectious uveitis (NIU) of the posterior segment (PS).DesignThree-year, phase III, multicenter, randomized, double-masked, controlled, prospective study (clinicaltrials.gov, NCT02746991).ParticipantsOverall, 153 patients in India with NIU-PS in ≥ 1 eye (with or without anterior uveitis) for ≥ 1 year who had ≥ 2 separate recurrences of uveitis requiring ocular injections or systemic therapy in the prior 12 months.MethodsPatients were randomized 2:1 for baseline FAi or sham injection and monitored for main outcome measures.Main outcome measuresIncidence and timing of uveitis recurrence, use of adjunctive therapy, best-corrected visual acuity, central foveal thickness, and monitoring of intraocular pressure (IOP)- and cataract-related events over 36 months.ResultsOverall, 153 patients (FAi, n = 101; treated sham, n = 52) were enrolled. Fluocinolone acetonide implant-treated eyes had significantly reduced uveitis recurrence rates versus treated sham (46.5% vs. 75.0%, respectively; P = 0.001) and a longer median time to recurrence (1116.0 [95% confidence interval, 847.00 to not evaluable] vs. 190.5 [95% confidence interval, 100.0-395.0] days for treated sham). Systemic adjunctive treatments were similar between groups, but fewer FAi-treated eyes required adjunctive injections (8.9% vs. 51.9% for treated sham). Visual outcomes were similar between groups, and residual macular edema was more common at 36 months in treated sham versus FAi-treated eyes (46.2% vs. 24.2%, respectively). The FAi-treated group had a lower central foveal thickness from month 12 onward. Intraocular pressure-lowering surgeries were stable in both groups, but, as expected, rates of IOP elevations were more frequent in the FAi-treated group than in the treated sham (IOP > 25 mmHg: 23.8% vs. 3.8%; IOP > 30 mmHg: 16.8% vs. 1.9%, respectively), and FAi-treated eyes had a higher incidence of cataract surgery than the treated sham (70.5% vs. 26.5%, respectively).ConclusionsIn patients with NIU-PS, the 0.2-μg/day FAi is associated with reduced-uveitis recurrence and increased time to first recurrence while controlling macular edema, maintaining stable IOP levels, and providing an expected safety profile, including a higher occurrence of cataract formation over 36 months.Financial disclosuresThe authors have no proprietary or commercial interest in any materials discussed in this article.

Dataset Information

Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial.

Objective

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Financial disclosure(s)

Publications

Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial.

Similar Datasets

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