Systemic, localized treatment both effective for uveitis

Baltimore-Both systemic and localized treatment for vision-threatening uveitis are effective in improving visual acuity and controlling uveitis and macular edema, according to results from the Multicenter Uveitis Steroid Treatment (MUST) trial as presented by Jennifer E. Thorne, MD, PhD, here at the 24th annual Current Concepts in Ophthalmology meeting.

“There were no statistically significant differences between groups in the primary outcome-BCVA-at the 2-year mark,” said Dr. Thorne, who is associate professor of ophthalmology and epidemiology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore. The improvement that we saw in vision was similar between the two treatment arms at both the 1-year and 2-year mark. The patients who had the most to gain-those whose vision was 20/40 or worse-tended to be the ones who had the most improvement, likely because of the control of the uveitis and the resolution of macular edema.”

Currently, the two modalities for the treatment of sight-threatening intermediate, posterior, and panuveitis are systemic treatment with either corticosteroids, immunosuppressive agents, or both and local treatment with the fluocinolone acetonide implant (Retisert, Bausch + Lomb), which provides a constant low-dose corticosteroid over a period of 2.5 years.

“With intermediate, posterior, and panuveitis, visual acuity can be affected,” Dr. Thorne said. “Loss of visual acuity is quite common. Uveitis is estimated to be the fifth to sixth leading cause of blindness in this country, with onset in all age groups. The uveitides are thought to affect working Americans more frequently than some of the other age-related diseases such as cataract and macular degeneration.”

The MUST trial is a 23-center, randomized, controlled, comparative effectiveness trial, Dr. Thorne explained. Patients were stratified based upon the type of uveitis they had and by the clinical site where they were enrolled. In all, 255 patients were randomly assigned to either systemic (n = 126) or implant (n = 129) therapy. Crossover rates and losses to follow-up were low, she noted.

“The MUST trial was designed to compare these two treatment modalities with a primary outcome of best-corrected visual acuity at the 2-year mark,” Dr. Thorne said. “Secondary outcomes included: control of uveitis, development of or prevention of complications in the eye related to uveitis, ocular and systemic side effects associated with treatment, and quality of life measures.”

At 2 years, the implant and the systemic therapy groups had a mean improvement in visual acuity of +6.0 and +3.2 letters, respectively (p = 0.16).

“You could see a slight but steady improvement in vision in both groups,” Dr. Thorne said.

Residual active uveitis remained in 12% of those in the implant therapy group and 29% of those in the systemic therapy group (p = 0.001). At 2 years, there was a 66% reduction in the level of uveitis activity in the group with the implants and a 46% reduction in the systemic group, and this was statistically significant (p = 0.001).

“Control of active uveitis occurred more quickly and more frequently in the implant group than in the systemic arm, although there was an impressive improvement with both therapies,” Dr. Thorne said.

“Both approaches did an excellent job at controlling the inflammation in the majority of patients, but control appeared to be faster and more frequent in our implant group. We saw cystoid macular edema resolution in both groups, and the difference was not statistically significant, which was somewhat surprising to us as investigators,” she concluded.

Patients assigned to the implant group had a higher risk of cataract surgery (hazard ratio [HR] = 3.3, p < 0.0001), treatment for elevated IOP (HR = 4.2, p < 0.0001), and glaucoma (HR = 4.2, p = 0.0008) when compared with those assigned to the systemic treatment arm. Despite these adverse events, the number of cases of intraoperative complications was low.

Patients assigned to the systemic therapy group experienced more infections requiring antibiotic treatment than those in the implant therapy group (0.60/person-year [PY] versus 0.36/PY, p = 0.034), but these carried no notable long-term consequences. The incidence rates of other systemic adverse events in both groups were low, with minimal differences between the two groups.

At 2 years, improvements in vision-related quality of life were higher in the implant arm compared with the systemic arm (+11.4 and +6.8 units, respectively; p = 0.043), as were changes in health utility of +0.02 and –0.02 units (p = 0.06).

“We did see some mild differences in general quality of life measures that modestly favored the implant group. On some of these factors, those changes were statistically significant, but they were not thought to be clinically meaningful changes,” Dr. Thorne said.

Reference

The Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: The Multicenter Uveitis Steroid Treatment Trial. Ophthalmology. 2011;118:1916-1926.

Dr. Thorne is the recipient of the RPB Sybil B. Harrington Special Scholar Award.

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