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Intravenous administration of the anti-interleukin-6 (IL-6) agent tocilizumab (Actemra, Genentech) is well-tolerated in patients with non-infectious uveitis involving the posterior segment and showing promising efficacy, according to interim outcomes reported by Quan Dong Nguyen, MD.
By Cheryl Guttman Krader
Las Vegas-Intravenous administration of the anti-interleukin-6 (IL-6) agent tocilizumab (Actemra, Genentech) is well-tolerated in patients with non-infectious uveitis involving the posterior segment and showing promising efficacy, according to interim outcomes reported by Quan Dong Nguyen, MD.
Speaking at the 2015 meeting of the American Academy of Ophthalmology, a total of 37 patients were entered at 5 sites across the United States into the investigator-sponsored study known as STOP-UVEITIS.
Patients were randomly assigned to receive tocilizumab 4 or 8 mg/kg. Treatment was initiated with 6 mandatory infusions at 1-month intervals. The primary endpoint was assessed at 6 months, and then tocilizumab administration was changed to an “as needed” basis.
“This is the first formal study looking at an IL-6 inhibitor for the treatment of uveitis,” said Dr. Nguyen, professor and chair of ophthalmology, University of Nebraska Medical Center, Omaha.
“Safety was most important, but we also looked at a number of exploratory efficacy outcomes and found that tocilizumab was associated with significant improvements in visual acuity, retinal edema, and vitreous haze,” he said. “In addition, its use allowed for a nice tapering of systemic corticosteroid treatment.
“Now we will continue to follow the patients and assess how well they do after starting on an as needed treatment regimen,” Dr. Nguyen said.
Tocilizumab is available in the United States with indications for treating juvenile idiopathic arthritis and rheumatoid arthritis.
Interest in investigating it as treatment of non-infectious uveitis was based on evidence that IL-6 causes ocular inflammation, is present in elevated levels in the vitreous of patients with active intermediate or posterior uveitis, and its inhibition resulted in improvement in an animal model of autoimmune uveoretinitis.
In addition, there are a few reports that tocilizumab was clinically effective for treating refractory uveitis and uveitic macular edema, Dr. Nguyen said.
Patients were eligible for the STOP-UVEITIS study if they had active noninfectious intermediate, posterior, or panuveitis. They could be treatment-naïve, on a systemic corticosteroid, and/or on a systemic immunomodulatory therapy, although the latter had to be discontinued within 30 days prior to starting tocilizumab.
The only adverse event recorded in this relatively small patient cohort was margination of neutrophils, which occurred in two patients and resolved after tocilizumab was withheld.
The exploratory efficacy analyses showed a steady increase in BCVA over time with a mean gain of about 8 letters at month 6. Central retinal thickness similarly decreased over time with an average decrease of about 84 µm from baseline to 6 months and of almost 200 µm among the 15 eyes with edema at baseline.
About three-fourths of eyes had a 1-step or greater decrease in vitreous haze grading, and over one-third had a 2-step or greater decrease in vitreous haze. Seven patients were on an oral corticosteroid at baseline at a mean (predisone equivalent) daily dose of 15.7 mg; at month 6, one patient remained on the systemic corticosteroid at a daily dose of 2 mg.
Subgroup analyses of the efficacy parameters suggested benefit for both doses.
STOP-UVEITIS is funded by a research grant from Genentech. Dr. Nguyen serves on the Scientific Advisory Board for Genentech.