Long-Term Results of a Monocentric Randomized Controlled Clinical Trial Comparing Interferon Beta With Methotrexate in the Treatment of Uveitis Macular Edema

Abstract

Introduction: : intermediate uveitis is frequently associated with macular edema (ME) which makes treatment additionally challenging. Here we want to present 1 year results and further follow-up of a randomized, controlled trial comparing interferon-β (IFN) and methotrexate (MTX).

Methods: : Local and federal authorities approval has been obtained. Patients with either primary uveitis or uveitis associated with multiple sclerosis 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 are randomized into either a therapy with IFN-β 44 µg s.c. 3 weekly or 20 mg MTX s.c weekly. After three months outcome parameters are assessed and efficacy determined. In case of treatment failure switch to the other treatment arm is possible.

Results: : so far 18 patients (5 with MS, 13 primary) could be included. Ten were randomized into the MTX, 8 into the IFN-β arm. 16 patients reached the three months time-point, two patients with MTX had to be excluded. Treatment was determined successful for the primary outcome parameter VA in 5 of 8 (63%) patients of the IFN-β group with a mean increase in VA of 0.33 log mar and in all patients for the secondary outcome decrease in ME (mean decrease in OCT thickness by 180 µm) but only 3 (30%) for VA in the MTX group (mean = 0.14 log mar) and two for ME (thickness increased by a mean 47 µm). The difference of VA in the IFN group was statistically siginificant (p=0.0078). Six of the MTX patients decided to switch to IFN-β, which lead to significant improvement. All IFN-β patients stayed on treatment, 10 have reached the study end of 12 months treatment with retained good VA and no or minimal amounts of ME. 7 patients are still on IFN up to 45 months of treatment with a mean of 26.5 months. 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: : Longterm results of the trial show superiority of IFN-β over MTX in the treatment of intermediate uveitis and ME. Treatment seems to be safe and effective even after over 2 years time. Even though the patient group is still small this treatment effect was statistically significant.

Clinical Trial: : www.clinicaltrials.gov NCT00344253

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