Multicenter Uveitis Steroid Treatment Trial: MUST Results

The Multicenter Uveitis Steroid Treatment Trial (MUST) compared two ways of treating noninfectious intermediate, posterior, and panuveitis: a fluocinolone acetonide implant in the eye, or systemic corticosteroids with immunosuppressive drugs when needed.

It is also the main randomized study of local versus systemic therapy in these diseases (see uveitic macular edema).

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Design of the Multicenter Uveitis Steroid Treatment Trial

The trial enrolled 255 patients, with 479 eyes, who had active or recently active disease. Investigators randomized them to a 0.59 milligram fluocinolone implant or to systemic therapy (see the references).

Patients in the systemic arm received oral prednisone, with immunosuppressive drugs, such as methotrexate, mycophenolate, or others, added when needed, and some received periocular steroids.

In addition, the primary outcome was the visual acuity at two years.

Multicenter Uveitis Steroid Treatment Trial: Visual Outcomes

Visual acuity improved in both groups, and the difference between them was small and not significant at two years (see the references).

At seven years the visual results were similar, and the finding suggests that both strategies protect vision when used well.

Control of Inflammation

The implant gave better control of inflammation in the treated eye, with fewer eyes with active uveitis and less macular edema in the early years.

Systemic therapy treated both eyes and the other organs involved, while the implant treated only one eye per implant.

Multicenter Uveitis Steroid Treatment Trial: Eye Side Effects of the Implant

• Cataract: nearly all phakic eyes needed cataract surgery
• Raised pressure: more eyes needed drops, and glaucoma surgery was more common than in the systemic arm (see steroid-induced glaucoma)
• Surgery: implant placement and removal need an operation

Systemic Side Effects

The systemic arm had more adverse events related to medicine, such as infections, anemia, and bone effects. The study found a similar rate of serious events overall.

Patients with systemic disease, bilateral involvement, or contraindications to the implant are better served by systemic therapy.

Multicenter Uveitis Steroid Treatment Trial: Quality of Life

Vision-related quality of life improved in both groups, and the scores were close at the end.

Which Patient for Which Option

• Implant: unilateral or asymmetric disease, a pseudophakic eye, the wish to avoid systemic drugs, and no history of steroid response
• Systemic therapy: bilateral disease, systemic features, a steroid responder, or a young phakic patient

Biologic drugs such as adalimumab have added a third option for noninfectious uveitis (see steroid-sparing immunosuppression in uveitis).

Multicenter Uveitis Steroid Treatment Trial: Practical Use

Check pressure often, monitor the lens, and shift to another approach when the pressure or cataract becomes a problem.

An Example Case

A 38-year-old woman has chronic unilateral intermediate uveitis with cystoid macular edema in the right eye despite periocular steroids.

She has had cataract surgery.

She declines systemic immunosuppression, and a fluocinolone implant is placed, which controls the inflammation and edema, with acuity improving from 20/80 to 20/30.

Her pressure rises to 27 mmHg at month six and is managed with two drops, and she is monitored regularly.

Practical Steps in the Clinic

• Exclude infection and masquerade syndromes before starting treatment (see uveitis masquerade syndromes)
• Test the pressure response with a short course of steroid if possible
• Discuss the plan for cataract and pressure before an implant
• Share care with a rheumatologist when the team chooses systemic therapy

Counselling the Patient

Explain that the study compared two reasonable ways to treat, that both gave similar vision, and that the differences were in the type of side effects.

Make clear that treatment may be needed for years, and that follow-up is long.

Key Points to Remember

• Vision outcomes were similar over years
• The implant controlled the inflammation better in the treated eye
• Cataract and glaucoma were more common with the implant
• Systemic therapy treats both eyes and other organs

Limits of the Study

The trial pre-dated the widespread use of adalimumab for noninfectious uveitis, so it does not tell how the implant compares with biologic drugs.

Patients were selected, and many centers have changed practice, but the comparison of local and systemic therapy remains a useful guide.

Looking Ahead

Trials are comparing biologic drugs, such as adalimumab, with other options, and are testing treatment strategies that aim to taper steroids.

Imaging with widefield angiography and OCT is also improving how disease activity is measured.

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References

1. Multicenter Uveitis Steroid Treatment 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.
2. Kempen JH, Altaweel MM, Drye LT, et al. Benefits of systemic anti-inflammatory therapy versus fluocinolone acetonide intraocular implant for intermediate uveitis, posterior uveitis, and panuveitis: fifty-four-month results of the Multicenter Uveitis Steroid Treatment (MUST) Trial. Ophthalmology. 2015;122:1967-1975.
3. Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130:492-513.
4. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 9: Uveitis and Ocular Inflammation. AAO; current edition.