Macular Edema, Ocular Sarcoidosis, Sarcoid-associated Uveitis
Conditions
Keywords
Sarcoid-associated uveitis, Macular oedema, Methotrexate, Conventional corticosteroids sparing agent.
Brief summary
The purpose of this study is to determine whether methotrexate is a effective corticosteroid sparing agent in the treatment of sarcoid-associated uveitis.
Detailed description
Macular oedema remains a significant cause of blindness. Corticosteroids are effective in the treatment of sarcoid-associated macular oedema but more than 50% of relapses occur when corticosteroids are tapered. Methotrexate (MTX) at low dose has been shown to be an effective and safe steroid-sparing agent for lung sarcoidosis and compilation of reported small series of patients with sarcoid-associated uveitis suggest that only 25% of relapses could be achieved with low dose MTX. We decide therefore to test the clinical efficacy of MTX in sarcoid-associated uveitis.
Interventions
DRUGMethotrexate
All patients will receive three pulses of methylprednisolone (5 mg/kg) followed by four weeks of prednisone (1 mg/kg daily). After randomization, patients will receive either prednisone (1 mg/kg daily) plus methotrexate (0.3 mg/kg weekly) or prednisone (1 mg/kg daily) plus placebo. Therapies will be administered orally. Corticosteroids will be progressively tapered when macular oedema completely resolve. Unilateral macular oedema relapses will be treated with a single local injection triamcinolone acetonide. Increasing dose of prednisone will be administered in case of bilateral macular oedema relapses.
DRUGPlacebo
All patients will receive three pulses of methylprednisolone (5 mg/kg) followed by four weeks of prednisone (1 mg/kg daily). After randomization, patients will receive either prednisone (1 mg/kg daily) plus methotrexate (0.3 mg/kg weekly) or prednisone (1 mg/kg daily) plus placebo. Therapies will be administered orally. Corticosteroids will be progressively tapered when macular oedema completely resolve. Unilateral macular oedema relapses will be treated with a single local injection of triamcinolone acetonide. Increasing dose of prednisone will be administered in case of bilateral macular oedema relapses.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients over 18 years old * Provided written consent for participation in the trial prior to any study-specific procedures or requirements * Posterior uveitis or panuveitis associated with macular oedema defined as increased macular thickness (more than 250 mm assessed by Stratus TD-OCT or 300 mm with Cirrus SD-OCT ) and/or the presence of cystoid spaces in the macula, and the absence of epiretinal membranes. * Patient with oral contraception * Posterior uveitis or panuveitis associated with macular oedema * Patients with histologically proven sarcoidosis or a presumed sarcoidosis. In case of a non caseating granuloma in biopsy tissues, the patients with presumed sarcoidosis meet at least 2 of the 4 following criteria: typical changes on chest radiography and computed tomography; predominantly CD4 lymphocytosis in bronchoalveolar lavage (BAL) fluid; elevated serum ACE levels; elevated gallium or 5 fluorodeoxyglucose uptake
Exclusion criteria
* Patients who do not fulfill the inclusion criteria * Other causes of uveitis * Extra ophthalmologic manifestations of sarcoidosis justifying corticosteroids * Patients previously treated with immunosuppressive agents or corticosteroids of more than 10 mg daily over 15 days. * Patients with life-threatening conditions * Chronic hepatopathy or renal failure * Uncontrolled diabetes mellitus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of macular oedema relapses. Every two weeks for five months, the amount of macular oedema will be assessed by Optical Coherence Tomography. | at 26 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Cumulated dose of prednisone | at 26 weeks |
| Number of triamcinolone injections | at 26 weeks |
| Adverse effects | at 26 weeks |
| Percentage of patients with best corrected visual acuity under 0.1, 0.2 and 0. | at 26 weeks |
| Percentage of patients with active anterior and /or posterior uveitis | at 26 weeks |
Countries
France
Outcome results
None listed