Antimetabolite Therapy for Uveitis: Methotrexate or Mycophenolate?

Effect of Corticosteroid-Sparing TreatmentWith Mycophenolate Mofetil vs Methotrexate on Inflammation in PatientsWith Uveitis: A Randomized Clinical Trial S. R. Rathinam, MD, PhD, John A. Gonzales, MD, Radhike Thundikandy,MD, et al. IMPORTANCE: Methotrexate andmycophenolate mofetil 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 ofmethotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. DESIGN, SETTING, AND PARTICIPANTS: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring 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, 25mg weekly (n = 107), or oralmycophenolate mofetil, 3 g daily (n = 109). MAIN OUTCOMES AND MEASURES: The primary outcomewas treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, 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 methotrexate group vs 56 (57.1%) in themycophenolate group (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 uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in themycophenolate group (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 uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3%[95%CI, -51.6%to 1.1%]; OR, 0.29 [95%CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in themycophenolate group. CONCLUSIONS AND RELEVANCE: Among adults with noninfectious uveitis, the use ofmycophenolate mofetil compared with methotrexate as first-line corticosteroidsparing 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.