Original article
Long-term Efficacy and Safety of Low-dose Interferon Alpha2a Therapy in Severe Uveitis Associated With Behçet Disease

https://doi.org/10.1016/j.ajo.2008.08.038Get rights and content

Purpose

To investigate long-term responsiveness of patients with severe uveitis associated with Behçet disease to interferon alpha2a (IFN-α2a).

Design

Retrospective study.

Methods

Thirty-two patients with sight-threatening uveitis associated with Behçet disease who relapsed despite corticosteroids and immunosuppressive agents were included. IFN-α2a was administered subcutaneously (three million units thrice a week). Ophthalmologic examination and fluorescein angiography associated with laboratory tests were performed at regular intervals. Main outcome measures were visual acuity and recurrence of uveitis attacks before, during, and after initiation of IFN-α2a therapy.

Results

Control of inflammation was achieved in 28 of 32 patients (88%). Mean observation period of the 28 responder patients was 70.6 months (range, 30.3 to 129.2 months). Median visual acuity improved from 0.52 to 0.33 (logarithm of the minimum angle of resolution units; P = .005) two years after initiation of IFN-α2a therapy. The relapse rate decreased significantly during IFN-α2a treatment from 1.68 ± 1.22 relapses/patient/year to 0.11 ± 0.20 relapses/patient/year (P < .0001). IFN-α2a was discontinued in 19 of 28 patients (68%) after 32 months of treatment (range, 16 to 50 months). Mean follow-up after IFN-α2a discontinuation was 43 months (range, 11 to 84 months). After IFN-α2a discontinuation, the relapse rate increased from 0.08 ± 0.21 relapse/person/year to 0.74 ± 1.40 relapse/person/year (P = 0.04).

Conclusions

IFN-α2a is efficient and safe for the long-term management of severe uveitis associated with Behçet disease. Meanwhile it seems to be a suspensive therapeutic strategy, even though long-term remission is possible in some patients.

Section snippets

Study Design

Clinical records of patients presenting with highly resistant ocular Behçet disease (according to the International Study Group's classification criteria31), and referred to the Ophthalmology and Internal Medicine Departments of the Pitié-Salpêtrière Hospital, Paris, France, between May 1995 and May 2004, for therapeutic management with IFN-α2a, were retrospectively reviewed. To be included, patients had to present active posterior uveitis or panuveitis, which had been refractory to at least

Patients

Thirty-two patients were included in this retrospective study, with a minimum of 16 months follow-up. Five patients were excluded from this study. Of these five patients, two were lost of follow-up, one had an insufficient follow-up time, one suffered from severe depression leading to permanent discontinuation of IFN-α2a after one month of treatment, and one, who was never treated with corticosteroids, suffered from an active hepatitis C. Median age was 30.3 years (range, 11 to 58 years) and

Discussion

Interferon-α2a has shown encouraging results in the treatment of Behçet disease alone or combined with corticosteroid and/or immunosuppressants.23, 29, 34, 35, 36, 37, 38 Several studies showed effectiveness of IFN-α2a in non-Behçet uveitis.26, 39, 40, 41 Initial treatment modalities, ie, doses ranging from three to nine MU daily vs thrice-a-week regimen, as well as duration of IFN-α2a administration and corticotherapy tapering, vary widely among reported studies. Kotter and associates recently

Julie Gueudry graduated from Rouen University School of Medicine, Rouen, France, in 2001. She completed her ophthalmology residency at University of Rouen Hospital and at University of Paris VI, Pitié-Salpêtrière Hospital, Paris, France. Since 2007, Dr Gueudry has started a fellowship in University of Rouen, Department of Ophthalmology.

References (54)

  • I. Kotter et al.

    The use of interferon alpha in Behçet disease: review of the literature

    Semin Arthritis Rheum

    (2004)
  • E. Bloch-Michel et al.

    International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease

    Am J Ophthalmol

    (1987)
  • J.A. Schulman et al.

    Posterior segment complications in patients with hepatitis C treated with interferon and ribavirin

    Ophthalmology

    (2003)
  • G. Perlemuter et al.

    Visual loss during interferon-alpha therapy in hepatitis C virus infection

    J Hepatol

    (2002)
  • C.P. Lohmann et al.

    Severe loss of vision during adjuvant interferon-alfa-2b treatment for malignant melanoma

    Lancet

    (1999)
  • N. Cassoux et al.

    Ocular manifestations of Behçet's disease

    Ann Med Interne (Paris)

    (1999)
  • S. Yurdakul et al.

    A double-blind trial of colchicine in Behçet's syndrome

    Arthritis Rheum

    (2001)
  • H. Yazici et al.

    A controlled trial of azathioprine in Behçet's syndrome

    N Engl J Med

    (1990)
  • R.B. Bhisitkul et al.

    Diagnosis and ophthalmological features of Behçet's disease

    Int Ophthalmol Clin

    (1996)
  • I. Cochereau-Massin et al.

    Ocular prognosis in Behçet's disease

    J Fr Ophtalmol

    (1992)
  • M. El Belhadji et al.

    Ophthalmological involvement in Behçet diseaseApropos of 520 cases

    J Fr Ophtalmol

    (1997)
  • E.W. Lindstedt et al.

    Anti-TNF-alpha therapy for sight threatening uveitis

    Br J Ophthalmol

    (2005)
  • S. Ohno et al.

    Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet's disease with refractory uveoretinitis

    J Rheumatol

    (2004)
  • E.B. Suhler et al.

    A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes

    Arch Ophthalmol

    (2005)
  • B. Wechsler et al.

    Infliximab in refractory uveitis due to Behçet's disease

    Clin Exp Rheumatol

    (2004)
  • S.L. Brown et al.

    Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration

    Arthritis Rheum

    (2002)
  • J. Keane et al.

    Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent

    N Engl J Med

    (2001)

    • Julie Gueudry graduated from Rouen University School of Medicine, Rouen, France, in 2001. She completed her ophthalmology residency at University of Rouen Hospital and at University of Paris VI, Pitié-Salpêtrière Hospital, Paris, France. Since 2007, Dr Gueudry has started a fellowship in University of Rouen, Department of Ophthalmology.

    View full text
    Copyright © 2008 Elsevier Inc. All rights reserved.