Methotrexate and Mycophenolate Mofetil for UVEITIS
Condition: Uveitis
MeSH terms: Uveitis
Intervention: Mycophenolate mofetil; Methotrexate; Prednisone
Intervention description: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID.; For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week); All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.
Intervention MeSH terms: Mycophenolic Acid; Prednisone; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 216.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: antimetabolite, noninfectious

Summary:

      In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, the
      investigators propose to establish which immunosuppressive therapy, methotrexate or
      mycophenolate mofetil, is more effective as a first-line, corticosteroid-sparing agent for
      the treatment of non-infectious uveitis in a block-randomized, observer-masked, comparative
      effectiveness trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All the following criteria must be met at enrollment:

        Historical non-infectious intermediate, anterior and intermediate, posterior or panuveitis
        in at least one eye

        Active inflammation within the last 180 days, defined by the presence of any of the
        following (in at least one eye) according to SUN criteria:

          -  ≥ 2+ anterior chamber cells

          -  ≥ 2+ vitreous haze

          -  active retinal or choroidal lesions

        Active inflammation at enrollment, defined by the presence of any of the following (in at
        least one eye) according to SUN criteria:

          -  ≥1+ anterior chamber cells and/or

          -  ≥1+ vitreous haze and/or

          -  active retinal/choroidal lesions

        At least one of the following criteria must be met before or at enrollment:

          -  Active inflammation after 4 weeks of high-dose (1mg/kg prednisone equivalent)
             corticosteroid treatment or 4 weeks following a regional corticosteroid injection

          -  Treatment with oral corticosteroids resulting in a reduction of inflammation, followed
             by an increase in inflammation (of at least 1 grade in anterior chamber cells or
             vitreous haze or a change of non-active to active lesions) when corticosteroid is
             tapered, in the 180 weeks prior to enrollment

          -  Active inflammation after long-acting corticosteroid injection 4 weeks to 180 days
             prior to enrollment

          -  Active inflammation after treatment with >10mg/day oral prednisone for at least the
             past 90 days prior to enrollment

          -  Known chronic condition necessitating corticosteroid-sparing immunosuppressive
             treatment: Behcet's disease with posterior segment involvement, multifocal choroiditis
             with panuveitis, serpiginous choroidopathy, birdshot retinochoroidopathy, diffuse
             retinal vasculitis, Vogt-Koyanagi-Harada with bullous serous retinal detachments
             and/or choroidal detachments, sympathetic ophthalmia. No prior therapy required for
             these patients

        Willingness to start corticosteroid treatment at 1mg/kg or 60mg a day of prednisone,
        whichever is less

        Willingness to limit alcohol consumption

        Willingness to use an acceptable method of contraception during the study period (i.e.
        pharmacologics, devices, barrier methods) or abstinence.

          -  Exclusion Criteria: Any of the following

        Any infectious cause of uveitis

        Prior immunosuppressive therapy other than corticosteroids in the past 12 months

        Prior intolerability or safety issues with methotrexate or mycophenolate mofetil

        Prior failure to control ocular or other inflammation using methotrexate or mycophenolate
        mofetil

        Prior biologic therapy at any time

        Media opacity (such as cataract and/or corneal scar) and/or extensive posterior synechiae
        such that examination of the posterior segment is not possible in both eyes

        Chronic hypotony (IOP < 5 mm Hg for > 3 months) in both eyes

        Periocular or intravitreal corticosteroid injection in the past 4 weeks

        Fluocinolone acetonide implant in either eye in < 3 years

        Intraocular surgery in < 30 days, or planning on getting surgery within the next 6 months

        Best spectacle-corrected visual acuity (BSCVA) of hand motions or worse in better eye

        < 16 years of age at enrollment

        Planning to conceive during the study period, pregnant or breast-feeding (blood or urine
        pregnancy test for all females, excluding those who are post-menopausal is mandatory)*

        Any history of cancer (If a patient has a history of non-melanoma skin cancer they can
        still be considered for inclusion in this study, provided it is not currently active).

        Systemic autoimmune disease anticipated to dictate treatment course

        Abnormal Complete blood count (≤ 2,500 white blood cells and/or ≤ 75,000 platelets and/or
        ≤9 hemoglobin) within 4 weeks prior to enrollment*

        Abnormal alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2 times
        the upper limit of normal for the lab and/or creatinine ≥ 1.5 within 4 weeks prior to
        enrollment*

        Evidence of active tuberculosis, HIV infection, syphilis, or hepatitis B or C (patients
        must have a tuberculin skin test, or interferon-gamma release assay, a chest radiograph,
        RPR/VDRL, FTA-ABS, or other treponemal tests, Hepatitis B surface antigen, Hepatitis C
        antibody tests, and HIV test within 90 days prior to enrollment)**

        *Testing required within 4 weeks prior to enrollment; **Testing required within 90 days
        prior to enrollment.