After seven years, NIH–funded clinical trial finds systemic therapy better preserves visual acuity and has fewer side effects.
Systemic therapy consisting of corticosteroids and immunosuppressants preserved vision of uveitis patients better – and had fewer adverse outcomes – than a long–lasting corticosteroid intraocular implant, according to a clinical trial funded by the National Eye Institute (NEI). After seven years, visual acuity on average remained stable among participants on systemic therapy but declined by an average of six letters among participants who had the implant.

“This trial provides good evidence that for the average patient with uveitis, systemic therapy would be the first choice of treatment,” said John Kempen, MD, PhD, of Massachusetts Eye and Ear/Harvard Medical School, Boston, chair of the writing committee for the report. “The visual outcome over the long run was better, on average, there were fewer adverse outcomes, and the cost is less.”

The findings were published in the Journal of the American Medical Association.

The fluocinolone intraocular implant, developed by Bausch & Lomb, was approved by the U.S. Food and Drug Administration in 2005. Early data suggested the implant was effective at controlling inflammation but had local ocular side effects. The Multicenter Uveitis Steroid Treatment Trial (MUST) was undertaken to evaluate whether the implant treatment was an improvement over systemic therapy for management of uveitis.

Researchers recruited 255 uveitis patients at 23 sites (21 in the U.S., one in the U.K., and one in Australia) and randomly assigned them to receive the fluocinolone implant or systemic treatment with corticosteroids and immunosuppressants, which are not FDA–approved for uveitis, inhibit pathological immune responses, thus reducing the amount of corticosteroids needed over the long–term, mitigating such side effects.

Through the first two years, the visual acuity remained about the same in the two groups (results published in 2011). At seven years, visual acuity on average remained stable in the systemic group but declined about six letters in the implant group. The researchers found that implant–treated eyes had reactivations of uveitis after about five years, which coincided with a decline in visual acuity. The loss of vision in the implant group appears to have been due to increased damage in the retina and choroid.

“These results emphasize the importance of longer follow–up for studies of treatments for chronic diseases that are likely to require years of treatment,” said Elizabeth Sugar, PhD, of Johns Hopkins University, Baltimore, chair of the statistical analysis committee for the MUST research group and lead statistician for the manuscript.

With respect to side effects, patients in the implant group were more likely to develop ocular side effects like cataracts, intraocular pressure elevation that required treatment with medicine and often surgery, and glaucoma. Patients receiving systemic therapy had increased risk of needing treatment with antibiotics, possibly due to immunosuppression, but otherwise did not have large increases in the risk of adverse effects typically associated with systemic corticosteroids such as high blood pressure or diabetes.

“We were able to avoid most of the systemic adverse outcomes that people worry about with systemic corticosteroid and immunosuppressive therapy by following expert panel guidelines. The result is meaningful not just in ophthalmology but in other disease areas, because many different fields use this strategy to treat the inflammatory diseases of many different organs,” said Kempen.