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Original Investigation
September 10, 2019

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

Author Affiliations
  • 1Uvea Services, Aravind Eye Hospitals and Postgraduate Institute of Ophthalmology, Madurai, India
  • 2F. I. Proctor Foundation, University of California, San Francisco
  • 3Department of Ophthalmology, University of California, San Francisco
  • 4Uvea Services, Aravind Eye Hospitals and Postgraduate Institute of Ophthalmology, Coimbatore, India
  • 5Uvea Services, Aravind Eye Hospitals and Postgraduate Institute of Ophthalmology, Pondicherry, India
  • 6Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia
  • 7Casey Eye Institute, Portland, Oregon
  • 8Oregon Health and Science University, Portland
  • 9OHSU-PSU School of Public Health, and VA Portland Health Care System, Portland, Oregon
  • 10Division of Vitreoretinal Surgery and Uveitis, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
  • 11Department of Epidemiology and Biostatistics, University of California, San Francisco
JAMA. 2019;322(10):936-945. doi:10.1001/jama.2019.12618
Visual Abstract.
Visual Abstract.
Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Uveitis
Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Uveitis
Key Points

Question  Is methotrexate or mycophenolate mofetil more effective as first-line immunosuppressive treatment for patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis requiring corticosteroid-sparing therapy?

Findings  In this randomized clinical trial of 216 patients with active noninfectious intermediate uveitis, posterior uveitis, and panuveitis, 66.7% of patients in the methotrexate group achieved corticosteroid-sparing control of inflammation compared with 57.1% in the mycophenolate group, a difference that was not statistically significant.

Meaning  Mycophenolate mofetil was not more effective than methotrexate in treating noninfectious uveitis.

Abstract

Importance  Methotrexate and mycophenolate 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 of methotrexate 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, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 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 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 the mycophenolate 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 the mycophenolate 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 the mycophenolate group.

Conclusions and Relevance  Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as 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

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