Purpose

To report outcomes of Vogt-Koyanagi-Harada (VKH) disease from a clinical trial of antimetabolite therapies.

Design

Subanalysis from an observer-masked randomized clinical trial for noninfectious intermediate, posterior, and panuveitis.

Methods

setting: Clinical practice at Aravind Eye Hospitals, India.

Patient population

Forty-three of 80 patients enrolled (54%) diagnosed with VKH.

Intervention

Patients were randomized to either 25 mg oral methotrexate weekly or 1 g mycophenolate mofetil twice daily, with a corticosteroid taper.

Main outcome measures

Primary outcome was corticosteroid-sparing control of inflammation at 5 and 6 months. Secondary outcomes included visual acuity, central subfield thickness, and adverse events. Patients were categorized as acute (diagnosis ≤3 months prior to enrollment) or chronic (diagnosis >3 months prior to enrollment).

Results

Twenty-seven patients were randomized to methotrexate and 16 to mycophenolate mofetil; 30 had acute VKH. The odds of achieving corticosteroid-sparing control of inflammation with methotrexate were 2.5 times (95% CI: 0.6, 9.8; P = .20) the odds with mycophenolate mofetil, a difference that was not statistically significant. The average improvement in visual acuity was 12.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. On average, visual acuity for patients with acute VKH improved by 14 more ETDRS letters than those with chronic VKH (P < .001), but there was no difference in corticosteroid-sparing control of inflammation (P = .99). All 26 eyes with a serous retinal detachment at baseline resolved, and 88% achieved corticosteroid-sparing control of inflammation.

Conclusions

The majority of patients treated with antimetabolites and corticosteroids were able to achieve corticosteroid-sparing control of inflammation by 6 months. Although patients with acute VKH gained more visual improvement than those with chronic VKH, this did not correspond with a higher rate of controlled inflammation.

Objective

To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis.

Design

Multicenter, block-randomized, observer-masked clinical trial.

Participants

Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India.

Intervention

Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered.

Main outcome measures

Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence.

Results

Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31).

Conclusions

There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.