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

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• 作者：Quan Dong Nguyen ; MD ; MSc¹ ; ^{quan.nguyen@unmc.edu" class="auth_mail" title="E-mail the corresponding author} ; Pauline T. Merrill ; MD² ; W. Lloyd Clark ; MD³ ; Alay S. Banker ; MD⁴ ; Christine Fardeau ; MD⁵ ; Pablo Franco ; MD⁶ ; Phuc LeHoang ; MD ; PhD⁵ ; Shigeaki Ohno ; MD ; PhD⁷ ; Sivakumar R. Rathinam ; FAMS ; PhD⁸ ; Stephan Thurau ; MD ; FEBO⁹ ; Abu Abraham ; MD¹⁰ ; Laura Wilson ; MD¹¹ ; Yang Yang ; PhD¹⁰ ; Naveed Shams ; MD ; PhD¹⁰ ; for the Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group^&lowast ;
• 关键词：BCVA ; best-corrected visual acuity ; CRT ; central retinal thickness ; IOP ; intraocular pressure ; mTOR ; mammalian target of rapamycin ; NEI VFQ-25 ; 25-item National Eye Institute Visual Function Questionnaire ; NIU ; noninfectious uveitis ; OCT ; optical coherence tomography ; SAKURA ; Sirolimus study Assessing double-masKed Uveitis tReAtment ; SAVE ; Sirolimus as a therapeutic Approach for uVEitis study ; VH ; vitreous haze
• 刊名：Ophthalmology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：123
• 期：11
• 页码：2413-2423
• 全文大小：1172 K

文摘

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.