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



Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus.



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.



Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120.



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.



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.



Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.
Ocular Imaging Research and Reading Center (OIRRC), Omaha, Nebraska. Electronic address: quan.nguyen@unmc.edu.
Quan Dong
QD
Nguyen
Department of Ophthalmology, Rush University Medical Center, Chicago, Illinois.
Pauline T
PT
Merrill
Palmetto Retina Center, LLC, West Columbia, South Carolina.
W Lloyd
WL
Clark
Banker's Retina Clinic and Laser Center, Navrangpura, Ahmedabad, India.
Alay S
AS
Banker
Department of Ophthalmology, Pitie-Salpetriere Hospital, University Pierre et Marie Curie, Paris VI, Paris, France.
Christine
C
Fardeau
Organización Médica de Investigación, Uruguay 725 PB, Buenos Aires, Argentina.
Pablo
P
Franco
Department of Ophthalmology, Pitie-Salpetriere Hospital, University Pierre et Marie Curie, Paris VI, Paris, France.
Phuc
P
LeHoang
Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
Shigeaki
S
Ohno
Aravind Eye Hospital, Madurai, Tamil Nadu, India.
Sivakumar R
SR
Rathinam
Department of Ophthalmology, Ludwig-Maximillians-University, Munich, Germany.
Stephan
S
Thurau
Santen, Inc., Emeryville, California.
Abu
A
Abraham
Genentech, Inc., South San Francisco, California.
Laura
L
Wilson
Santen, Inc., Emeryville, California.
Yang
Y
Yang
Santen, Inc., Emeryville, California.
Naveed
N
Shams
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D057972:Posterior Eye Segment / Q000473:pathology*; D012160:Retina / Q000473:pathology*; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D013997:Time Factors; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014605:Uveitis / Q000175:diagnosis / Q000188:drug therapy*; D014792:Visual Acuity; D055815:Young Adult
D007166:Immunosuppressive Agents; D020123:Sirolimus