Differential efficacy of human recombinant interferon-α2a on ocular and extraocular manifestations of behçet disease: results of an open 4-center trial

https://doi.org/10.1016/j.semarthrit.2003.09.005Get rights and content

Abstract

Objective

Behçet disease (BD) is a multisystem vasculitis of unknown origin. Standard treatment mainly comprises systemic immunosuppressive agents. In a study primarily designed for refractory ocular disease, we additionally evaluated the efficacy of recombinant human interferon-α2a (rhIFN-α2a) on the extraocular manifestations of BD.

Methods

Fifty patients were included in the study. RhIFN-α2a was applied at a dose of 6 × 106 units subcutaneously daily. Dose reduction was performed according to a decision tree until discontinuation. Disease activity was evaluated by the Behçet’s Disease Activity Scoring System and the Uveitis Scoring System.

Results

Response rate of the ocular manifestations was 92%. Visual acuity rose significantly from 0.56 to 0.84 at week 24 (P < .0001). Mean Behçet’s Disease Activity Score fell in a dose-dependent fashion by 1.2 points in the first week (P < .0001) and from 5.8 to 3.3 at week 24 and further to 2.8 at week 52. After a mean observation period of 36.4 months, 17 patients have been off treatment and disease-free for 29.5 months (mean). In the other patients, maintenance IFN dosage is 3 million units 3 times weekly. Whereas extraocular manifestations such as genital ulcerations, arthritis, and skin lesions remitted with IFN, only 36% of oral aphthous ulcers responded.

Conclusions

RhIFN-α2a is effective in ocular BD, resulting in significant improvement of vision and complete remission of ocular vasculitis in the majority of patients. It is also beneficial for the extraocular manifestations of the disease, although less so for oral aphthous ulcers.

Section snippets

Study design

Fifty patients with refractory ocular BD were included in 4 participating hospitals between March 1995 and March 2000. The final evaluation was performed in March 2001. Forty-six patients fulfilled the International Study Group Criteria (16), and 4 patients had incomplete BD with typical oral aphthous ulcers and panuveitis with occlusive retinal vasculitis and/or hypopion. The study protocol (adhering to the Declaration of Helsinki) had been approved by the Ethics Committee of each hospital and

Results

Fifty patients were included (9 in Essen, 5 in Freiburg, 2 in Göttingen, 34 in Tübingen). The mean age was 32 years (SD, 7.6, range, 21–52, years) male:female ratio, 36:14, and mean duration of BD was 5.2 (SD, 4.8, range, 0–19) years. HLA-B51 was positive in 41 patients (81%). All 50 patients had typical oral aphthous ulcers (100%), 38 patients had cutaneous manifestations (76%), 26 had genital ulcers (52%), 24 had arthritis (48%), 3 patients had vascular manifestations (deep vein thrombosis)

Discussion

Severe, sight-threatening ocular disease usually is treated with AZA or CSA 23, 27, 28, 29, 30. In refractory cases, combinations of both drugs with glucocorticosteroids or cyclophophamide or chlorambucil have been used 30, 31, 32, 33, 34, sometimes with serious side effects such as renal insufficiency (when CSA at more than 5 mg/kg was required) or secondary malignancy 29, 35, 36. In the present study, rhIFN-α2a was primarily instituted to treat severe refractory ocular BD. For this

Acknowledgements

The authors thank Prof C. A. Müller, Tübingen, for the HLA-analysis; Prof R. Klein, Tübingen, for the detection of autoantibodies; U. Rückwaldt and S. Koch for their technical assistance; and Prof Graham Pawelec, Tübingen, for his critical review of the manuscript.

Ina Kötter, MD: University Hospital, Department of Internal Medicine II (Hematology, Oncology, Immunology, and Rheumatology), Tübingen, Germany

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    Ina Kötter, MD: University Hospital, Department of Internal Medicine II (Hematology, Oncology, Immunology, and Rheumatology), Tübingen, Germany

    Reinhard Vonthein, PhD: University Hospital, Department of Medical Biometry, Tübingen, Germany

    Manfred Zierhut, MD: University Hospital, Department of Ophthalmology, Tübingen, Germany

    Anja Katrin Eckstein, MD: University Hospital, Department of Ophthalmology, Essen, Germany

    Thomas Ness, MD: University Hospital, Department of Ophthalmology, Freiburg, Germany

    Ilhan Günaydin, MD: University Hospital, Department of Internal Medicine II (Hematology, Oncology, Immunology, and Rheumatology), Tübingen, Germany;

    Bodo Grimbacher, MD: University Hospital, Department of Internal Medicine, Division of Clinical Immunology and Rheumatology, Freiburg, Germany

    Sabine Blaschke, MD: University Hospital, Department of Internal Medicine, Division of Nephrology and Rheumatology, Göttingen, Germany

    Hans Hartmut Peter, MD: University Hospital, Department of Internal Medicine, Division of Clinical Immunology and Rheumatology, Freiburg, Germany

    Nicole Stübiger, MD: University Hospital, Department of Ophthalmology, Tübingen, Germany

    View full text