Multicenter Uveitis Steroid Treatment (MUST) Trial

To compare the efficacy of standardized systemic therapy versus fluocinolone acetonide implant therapy for the treatment of severe cases of non-infectious intermediate uveitis, posterior uveitis, or panuveitis.

Uveitis refers to several ocular diseases characterized by intraocular inflammation and is a major cause of visual loss and blindness in the United States. Intermediate uveitis, posterior uveitis, and panuveitis are generally the more severe forms of uveitis that result in the highest incidence of vision loss and often requiring long-term systemic treatment with oral corticosteroids, sometimes in conjunction with other immunosuppressive agents. A local therapy approach that accomplishes long-term control of inflammation and avoids systemic side effects would be desirable. Based on prelimanry studies, the fluocinolone acetonide implant appears to be a promising local therapy which may have advantages and disadvantages in comparison with standard systemic therapy. Although the study leading to FDA approval of the fluocinolone acetonide implant demonstrated its efficacy in controlling inflammation in these types of uveitides, there are no data comparing the long term visual outcomes of the implant to conventional systemic corticosteroid/immunosuppressive drug therapy. Further, data on comparative risks of these two types of therapy are sparse. As such the role (timing, indications vis-à-vis systemic therapy) of the implant in the management of patients with severe intermediate, posterior, or panuveitis remains to be established. The MUST trial will directly address these issues.

The MUST Trial will enroll patients whose uveitis is severe enough to require systemic therapy. The MUST Trial will compare the efficacy of the fluocinolone acetonide implant with standardized systemic therapy.

The MUST Trial is a randomized controlled clinical trial comparing two treatments for patients with vision-threatening non-infectious intermediate uveitis, posterior uveitis, or panuveitis: 1) local therapy with fluocinolone acetonide intraocular implant in affected eyes; versus 2) standard therapy: systemic corticosteroid therapy supplemented, when indicated, by corticosteroid-sparing potent immuno-modulator therapy. Study ophthalmologists, clinic coordinators, and patients will not be masked to treatment assignment. Masking will be applied to the determination of visual function (at baseline, the six month visit, and all subsequent follow-up visits), those outcomes based on photographic reading, blood pressure measurements, laboratory studies, and diagnosis of glaucoma by the glaucoma outcomes committee. Patients will be followed until death, participant withdrawal, or a common study closeout. Patients will be seen at baseline, one month after randomization, three months after randomization, and every three months thereafter for data collection. Both ophthalmological and medical data will be collected to evaluate the outcomes of treatment of the uveitis, complications of the uveitis, and complications from therapy itself. Selected laboratory data related to the complications from systemic corticosteroid therapy will be collected.

The planned sample size of 250 patients, 125 per treatment group, is expected to give sufficient power to detect clinically important differences in visual acuity outcomes. Patients meeting the eligibility criteria detailed above will be enrolled at approximately 23 clinical centers in the United States, Australia and UK and randomized on a 1:1 basis to one of the two treatment groups.

Patients with active non-infectious intermediate uveitis, posterior uveitis, or panuveitis for whom oral corticosteroid therapy is indicated are eligible for the MUST Trial. Current or past use of oral corticosteroids or other immunosuppressive agents for uveitis is acceptable. Previous use of fluocinolone acetonide therapy also is acceptable if any implant still present in an eye was placed more than 3 years previously. Uveitis with or without an associated systemic disease is acceptable; however, the systemic disease must not be sufficiently active that it dictates therapy with oral corticosteroids or other immunosuppressive agents at the time of study entry.

Specific inclusion criteria include:

Specific exclusion criteria include: