Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients With Uveitis: A Randomized Clinical Trial

Importance Methotrexateand mycophenolatemofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective To compare the effect of methotrexateand mycophenolatefor achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants The First-line Antimetabolitesas Steroid-sparing Treatment (FAST) uveitistrial screened 265 adults with noninfectious uveitisrequiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolatemofetil, 3 g daily (n = 109). Main Outcomes and Measures The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexategroup vs 56 (57.1%) in the mycophenolategroup (difference, 9.5% [95% CI, −5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81];P = .20). Among patients with posterior uveitisor panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexategroup vs 42 (55.3%) in the mycophenolategroup (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90];P = .02); whereas among patients with intermediate uveitistreatment success occurred in 6 (33.3%) in the methotrexategroup vs 14 (63.6%) in the mycophenolategroup (difference, −30.3% [95% CI, −51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05];P = .07;Pfor interaction = .004). Elevated liver enzymeswere the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexategroup and 8 patients (7.4%) in the mycophenolategroup. Conclusions and Relevance Among adults with noninfectious uveitis, the use of mycophenolatemofetil compared with methotrexateas first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis. Trial Registration ClinicalTrials.gov Identifier:NCT01829295