First-line Antimetabolites as Steroid-sparing Treatment Uveitis Pilot Trial
Condition: Uveitis
MeSH terms: Uveitis
Intervention: Methotrexate; Mycophenolate mofetil
Intervention description: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.; Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
Intervention MeSH terms: Mycophenolic Acid; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 80.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: uveitis; antimetabolite; immunosuppressive; clinical trial

Summary:

      The proposed study is a masked trial, with stratified block randomization by site, designed
      to determine which treatment, methotrexate or mycophenolate mofetil, is more effective as
      first-line steroid-sparing treatment for patients with non-infectious uveitis requiring
      corticosteroid-sparing therapy.

      One hundred non-infectious uveitis patients in need of corticosteroid-sparing therapy will be
      randomized to receive either oral methotrexate or oral mycophenolate mofetil at Aravind Eye
      Hospitals (Madurai and Coimbatore, South India). They will be followed monthly for 6 months
      after enrollment or until treatment failure. The investigators hypothesize that the
      proportion achieving corticosteroid-sparing success at 6 months for patients taking
      mycophenolate mofetil will be improved in comparison with patients taking methotrexate.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Non-infectious anterior, intermediate, posterior or panuveitis

          -  Active uveitis within the last 60 days (defined by the presence of any of the
             following according to SUN criteria: ≥ 1+ anterior chamber cells, anterior vitreous
             cells, vitreous haze, active retinal or choroidal lesions)

          -  Prednisone dose ≥ 15 mg/day

          -  History of corticosteroid taper failure (inability to taper to prednisone 10 mg or
             less) or obvious chronic disease necessitating corticosteroid-sparing
             immunosuppressive treatment

        Exclusion Criteria:

          -  Any infectious cause of uveitis

          -  Tuberculosis: Evidence of active TB (PPD and CXR required - latent TB patients are
             still eligible)

          -  Positive for Hepatitis: HBsAg and/or Hep C antibody

          -  Positive for Syphilis: RPR/VDRL and/or FTA-ABS

          -  Abnormal CBC (<2500 WBC or <75,000 Plts or <10 Hgb)

          -  Abnormal liver and/or kidney tests (ALT/AST >2x normal or CR>1.5)

          -  Pregnancy or breast-feeding (blood or urine pregnancy test for all females, excluding
             those who are post-menopausal)

          -  Chronic hypotony (IOP < 5 mm Hg for > 3 months)

          -  Prior use of any immunosuppressive drug for the treatment of uveitis in the past 6
             months

          -  Prior failed treatment with methotrexate or mycophenolate mofetil

          -  Periocular or intravitreal corticosteroid injection in the past 3 months

          -  Fluocinolone acetonide implant surgery in either eye in < 3 years

          -  Intraocular surgery in < 30 days, or any ocular surgery scheduled during the 6-month
             study period

          -  VA of hand motions or worse in better eye

          -  < 16 years of age at enrollment