Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA)

Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group

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Abstract

Purpose To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Design Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Participants Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Methods Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. Main Outcome Measures The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. Results A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Conclusions Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.

Original languageEnglish (US)
Pages (from-to)2413-2423
Number of pages11
JournalOphthalmology
Volume123
Issue number11
DOIs
StatePublished - Nov 1 2016

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Uveitis
Sirolimus
Double-Blind Method
Posterior Uveitis
Adrenal Cortex Hormones
Panuveitis
Visual Acuity
Prednisone
Outcome Assessment (Health Care)
Inflammation
Safety
Control Groups
Incidence

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Intravitreal Sirolimus for Noninfectious Uveitis : A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA). / Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group.

In: Ophthalmology, Vol. 123, No. 11, 01.11.2016, p. 2413-2423.

Research output: Contribution to journalArticle

Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group 2016, 'Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA)', Ophthalmology, vol. 123, no. 11, pp. 2413-2423. https://doi.org/10.1016/j.ophtha.2016.07.029
Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group. / Intravitreal Sirolimus for Noninfectious Uveitis : A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA). In: Ophthalmology. 2016 ; Vol. 123, No. 11. pp. 2413-2423.
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title = "Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA)",
abstract = "Purpose To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Design Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Participants Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Methods Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. Main Outcome Measures The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. Results A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8{\%}; P = 0.025) and 880 μg (16.4{\%}; P = 0.182) groups met the primary end point than in the 44 μg group (10.3{\%}). Likewise, higher proportions of subjects in the 440 μg (52.6{\%}; P = 0.008) and 880 μg (43.1{\%}; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0{\%}). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6{\%}], 440 μg [76.9{\%}], and 880 μg [66.7{\%}]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Conclusions Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.",
author = "{Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group} and Nguyen, {Quan Dong} and Merrill, {Pauline T.} and Clark, {W. Lloyd} and Banker, {Alay S.} and Christine Fardeau and Pablo Franco and Phuc LeHoang and Shigeaki Ohno and Rathinam, {Sivakumar R.} and Stephan Thurau and Abu Abraham and Laura Wilson and Yang Yang and Naveed Shams",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.ophtha.2016.07.029",
language = "English (US)",
volume = "123",
pages = "2413--2423",
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TY - JOUR

T1 - Intravitreal Sirolimus for Noninfectious Uveitis

T2 - A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA)

AU - Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group

AU - Nguyen, Quan Dong

AU - Merrill, Pauline T.

AU - Clark, W. Lloyd

AU - Banker, Alay S.

AU - Fardeau, Christine

AU - Franco, Pablo

AU - LeHoang, Phuc

AU - Ohno, Shigeaki

AU - Rathinam, Sivakumar R.

AU - Thurau, Stephan

AU - Abraham, Abu

AU - Wilson, Laura

AU - Yang, Yang

AU - Shams, Naveed

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Purpose To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Design Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Participants Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Methods Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. Main Outcome Measures The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. Results A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Conclusions Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.

AB - Purpose To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Design Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Participants Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Methods Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. Main Outcome Measures The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. Results A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Conclusions Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.

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