First Results of a Randomized Controlled Clinical Trial Comparing Interferon Beta With Methotrexate for the Treatment of Intermediate Uveitis With Macular Edema

Abstract

Purpose: : Intermediate uveitis is frequently associated with macular edema (ME) which makes treatment additionally challenging. In a retrospective pilot study we could show the efficacy of interferon-beta (IFN-ß) in a series of 13 patients. Here we want to present first results of a randomized, controlled trial.

Methods: : Local and federal authorities approval has been obtained. Patients with either primary uveitis or uveitis associated with multiple sclerosis (MS) are eligible. Main inclusion criteria are reduced visual acuity (VA) of 20/30 or less and ME as measured by OCT with central 1mm values of at least 250 µm. Patients fulfilling all inclusion and no exclusion criteria are randomized into either a therapy with IFN-ß 44 µg s.c. 3 weekly or 20 mg methotrexate (MTX) s.c weekly. After three months of therapy main outcome parameters are assessed and efficacy determined. In case of treatment failure switch to the other treatment arm is possible.

Results: : So far 13 patients (3 with MS, 10 primary) could be included. Seven were randomized into the MTX, 6 into the IFN-ß arm. 10 patients reached the three months time-point, one patient with MTX had to be excluded from evaluation for not complying to the study protocol. The 2 remaining patients have not yet reached the 3 months time point. Treatment was determined successful for the primary outcome parameter VA in 5 of 6 (83%) patients of the IFN-ß group with a mean increase in VA of 0.3 log mar and in all 6 patients for the secondary outcome decrease in macular edema (mean decrease in central OCT thickness by 189 µm) but only 2 (50%) for VA in the MTX group (mean = 0.16 log mar) and none for macular edema (thickness increased by a mean 44 µm). All MTX patients decided to switch to IFN-ß, which lead to significant improvement. All IFN-ß patients stayed on treatment, 4 have reached the study end of 12 months treatment with retained good VA and no or minimal amounts of ME. A mean of 6 mild to moderate adverse events (AE) per patient were seen in the IFN group with one not-drug related serious AE (hypertensive episode) versus a mean 4 AE in the MTX group.

Conclusions: : First results of the trial show superiority of IFN-ß over MTX in the treatment of intermediate uveitis and ME. More patients have to be included to have the sufficient power to decide if this treatment effect is significantly bigger.

Clinical Trial: : www.clinicaltrials.gov NCT00344253

Keywords: clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • uveitis-clinical/animal model