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.

• Authors: Quan Dong Nguyen, Pauline T Merrill, W Lloyd Clark, Alay S Banker, Christine Fardeau, Pablo Franco, Phuc LeHoang, Shigeaki Ohno, Sivakumar R Rathinam, Stephan Thurau, Abu Abraham, Laura Wilson, Yang Yang, Naveed Shams, Sirolimus study Assessing double-masKed Uveitis tReAtment (SAKURA) Study Group
• Journal: Ophthalmology (Ophthalmology) Vol. 123 Issue 11 Pg. 2413-2423 (11 2016) ISSN: 1549-4713 [Electronic] United States
• PMID: 27692526 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunosuppressive Agents
• Sirolimus

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Immunosuppressive Agents (administration & dosage)
• Intravitreal Injections
• Male
• Middle Aged
• Posterior Eye Segment (pathology)
• Retina (pathology)
• Retrospective Studies
• Sirolimus (administration & dosage)
• Time Factors
• Tomography, Optical Coherence
• Treatment Outcome
• Uveitis (diagnosis, drug therapy)
• Visual Acuity
• Young Adult