Association between long-lasting intravitreous fluocinolone acetonide implant vs systemic anti-inflammatory therapy and visual acuity at 7 years among patients with intermediate, posterior, or panuveitis

John H. Kempen, Michael M. Altaweel, Janet Teresa Holbrook, Elizabeth Sugar, Jennifer Thorne, Douglas Jabs

Research output: Contribution to journalArticle

Abstract

IMPORTANCE A 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. OBJECTIVE To 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 PARTICIPANTS Nonprespecified 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). INTERVENTIONS Participants 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 MEASURES Primary 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. RESULTS Seven-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 RELEVANCE In 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.

Original languageEnglish (US)
Pages (from-to)1993-2005
Number of pages13
JournalJAMA - Journal of the American Medical Association
Volume317
Issue number19
DOIs
StatePublished - May 16 2017

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Fluocinolone Acetonide
Panuveitis
Visual Acuity
Anti-Inflammatory Agents
Uveitis
Therapeutics
Adrenal Cortex Hormones
Immunosuppression
Randomized Controlled Trials
Steroids
Metabolic Bone Diseases
Immunosuppressive Agents
Group Psychotherapy
Hyperlipidemias

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{779bc2d3e3464def897284c5221112e0,
title = "Association between long-lasting intravitreous fluocinolone acetonide implant vs systemic anti-inflammatory therapy and visual acuity at 7 years among patients with intermediate, posterior, or panuveitis",
abstract = "IMPORTANCE A 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. OBJECTIVE To 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 PARTICIPANTS Nonprespecified 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). INTERVENTIONS Participants 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 MEASURES Primary 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. RESULTS Seven-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 RELEVANCE In 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.",
author = "Kempen, {John H.} and Altaweel, {Michael M.} and Holbrook, {Janet Teresa} and Elizabeth Sugar and Jennifer Thorne and Douglas Jabs",
year = "2017",
month = "5",
day = "16",
doi = "10.1001/jama.2017.5103",
language = "English (US)",
volume = "317",
pages = "1993--2005",
journal = "JAMA - Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
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TY - JOUR

T1 - Association between long-lasting intravitreous fluocinolone acetonide implant vs systemic anti-inflammatory therapy and visual acuity at 7 years among patients with intermediate, posterior, or panuveitis

AU - Kempen, John H.

AU - Altaweel, Michael M.

AU - Holbrook, Janet Teresa

AU - Sugar, Elizabeth

AU - Thorne, Jennifer

AU - Jabs, Douglas

PY - 2017/5/16

Y1 - 2017/5/16

N2 - IMPORTANCE A 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. OBJECTIVE To 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 PARTICIPANTS Nonprespecified 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). INTERVENTIONS Participants 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 MEASURES Primary 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. RESULTS Seven-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 RELEVANCE In 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.

AB - IMPORTANCE A 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. OBJECTIVE To 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 PARTICIPANTS Nonprespecified 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). INTERVENTIONS Participants 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 MEASURES Primary 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. RESULTS Seven-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 RELEVANCE In 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.

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