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Interferon alpha may offer improved vision for Behçet's disease patients INTERFERON-ALPHA2a (IFNa2a) treatment can produce significant improvement of vision and complete remission of ocular vasculitis in patients with severe ocular Behçet's disease, according to the results of a German multicentre trial. "The mode of action is still unknown. It may be superior to the standard immunosuppressive treatment with respect to the possibility of complete tapering without relapse," notes Manfred Zierhut MD, who together with his associate at the University of Tuebingen , Dr Kötter, is a chief investigator in the trial. Dr Zierhut presented the results obtained in the first 50 patients treated with interferon-alpha for Behçet's disease. The study enrolled 31 Turkish and 10 German patients and nine from Mediterranean countries all with severe, refractory, sight threatening panuveitis or uveitis posterior due to Behçet´s disease.
Among responders visual acuity rose significantly from 0.56 to 0.84 at week 24 (p<0.0001). Posterior uveitis score of the affected eyes fell by 46% every week (p<0.001). All 77 of the affected eyes reached remission score by week 24. The mean Behçet's Disease Activity Score fell from 6.6 to 3.1 at week 24 and further to 1.8 at week 52. After a mean observation period of 36.4 months (range 12 - 74), 20 patients (40 %) have been off treatment and have been disease free for seven to 58 months (mean 29.5). The remaining responding patients had relapses and are receiving maintenance dosage of three million IU of interferon three times weekly. Side effects from the therapy were dose dependent and relatively mild. The major side effects were fibromyalgia in five patients and exacerbation of psoriasis in two patients who have had a history of the disease. Eight patients developed ANA antibodies and one had double-stranded DNS antibodies, but none of these patients developed clinical lupus. Three patients had anti-thyroid antibodies and two of them later developed thyroiditis. Remarkably, none of the patients produced anti-interferon antibodies. Comparing these results with previous studies, Dr Zierhut pointed out that one of his co-workers, Dr. Deuter, has recently analysed the five-year visual acuity data for 15 eyes in nine patients. The visual acuity improved in 10 eyes and remained constant in five. Not one eye deteriorated. None of the eyes developed optic nerve atrophy after treatment with interferon-alpha.
"There are concerns about the side effects of the interferon therapy and other anecdotal reports, which would suggest that retinal vascular disease can be a complication of this therapy. So I think it's very provocative but I think most people would like to see a little more information in a rigorously run controlled trial," Dr Nussenblatt told EuroTimes Dr Zierhut pointed that such retinal complications have been reported when interferon alpha has been used for treatment in tumour or hepatitis patients, but not as yet in any Behçet's patients. Dr Zierhut presented his study earlier this year at the 2003 annual meeting of the Association for Research in Vision and Ophthalmology. Manfred Zierhut , MD National Eye Institute
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"We started with six million IU of interferon-alpha2a in men, and three million IU in women. The women are more likely to suffer flu-like symptoms, which is typical for interferon alpha," he noted. Dose reduction was performed according to a decision tree until discontinuation. Disease activity was evaluated every second week using the Behçet's Disease Activity Scoring System and the Uveitis Scoring System. "We saw that 92% of the 50 patients completely responded to this therapy. Only four patients did not respond completely. Of those, three went blind despite other immunosuppressive drugs, and one needed additional treatment. There were also compliance problems. One patient showed a partial response. He needed very high doses of alpha interferon and a combination of alpha and gamma interferon, before he was able to control his situation," Dr Zierhut said. 
Looking to the future, Dr Zierhut is planning a controlled randomised study, matching IFN2a against cyclosporine A, the only treatment, which has been studied in a controlled study before for Behçet's disease. "Until that time, we will treat all patients with retinal vasculitis that is becoming occlusive with interferon-alpha. Compared to other immunosuppressive drugs, alpha interferon seems interesting in that we don't need a prophylactic treatment because it is effective in a very short time. All the patients in our study who had recurrences received repeat interferon treatment, and all improved. This is important. If these people don't respond to interferon-alpha, we will probably switch to other immunosuppressive drugs, probably to TNF alpha blockers, which have been reported to be also effective, but have not have not had longterm observation," Dr Zierhut added. Robert B. Nussenblatt MD, of the National Eye Institute, urged caution in the interpretation of the results from the study. He emphasised the need for a randomised controlled clinical study.