Clinical trial NCT00167583: Interferon-alpha2a Versus Cyclosporin A for Severe Ocular Behcet's Disease (INCYTOB)
Official title: Phase III Study of Recombinant Human Interferon-alpha2a Versus Cyclosporin A for the Treatment of Ocular Behcet's Disease - a National,Randomised, Single-masked Controlled Trial (INCYTOB)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Behcet's Disease
Panuveitis
Posterior Uveitis
Retinal Vasculitis
Keywords: Ocular Behcet's disease
Panuveitis
Posterior Uveitis
Retinal vasculitis
Treatment
Interferon-alpha
Cyclosporin A
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2005-09-14
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate if interferon-alpha2a is superior to the standard treatment with cyclosporin A for the treatment of severe ocular manifestations of Behcet's disease.

Detailed description: Behcet's disease is a multisystem vasculitis often involving ocular (retinal) blood vessels (in 70% of all cases). This form of uveitis or retinal vasculitis still leads to blindness in 25 to 50% of the patients irrespective of immunosuppressive treatment.

The aim of the study is to evaluate if Interferon-alpha2a is superior to the present standard treatment (cyclosporin A (CSA)) for severe ocular (panuveitis, posterior uveitis, retinal vasculitis) Behçet's Disease (BD) and significantly improves visual prognosis and quality of health and life of the patients with ocular BD and is acting more rapidly than standard treatment. Furthermore, we want to evaluate if IFN-α induces long term remissions of ocular BD which can be maintained without further medical treatment.

The patients are randomised into two treatment groups (IFN/CSA) and treated for one year according to an algorithm which adapts dosages to clinical course. A crossover from one treatment arm to the other is planned in case of inefficacy.

Eligibility criteria: Inclusion Criteria:

* Behçet's disease fulfilling the International Study Group Criteria with active pan- or posterior uveitis (according to the posterior uveitis scoring system) or retinal vasculitis and active disease according to the Behcet's Disease activity scoring system.

Exclusion Criteria:

* Previous treatment with interferon-α or cyclosporin A
* Pregnancy, breast feeding women, malignancy
* Renal impairment (creatinine \> 1.5 mg/dl)
* Uncontrolled hypertension or diabetes
* Depression or other psychic disorders(also history of depression)
* History of acute or chronic inflammatory joint or autoimmune disease
* Organ or bone marrow transplant recipient, cardiac failure \> NYHAIII
* Acute liver disease with SGPT 2x above normal
* White blood cell count \< 3500/mm3
* Platelet count \< 100000/mm3
* Hgb \< 8.5g/dl
* Body weight \<45 kg
* Alcohol abuse or drug abuse
* Mental impairment
* Uncooperative attitude

Primary outcomes:
measure: Improvement of disease activity and preservation of visual acuity (monthly, at one and 2 years)
timeFrame: 2 years
measure: Time to improvement and remission
timeFrame: 2 years
Secondary outcomes:
measure: Laboratory values for inflammatory activity (monthly)
timeFrame: 2 years
measure: Number of switches from one treatment to the other
timeFrame: 2 years
measure: Quality of life for patients with low vision (monthly)
timeFrame: 2 years
measure: Number of ocular and non-ocular relapses (1 year, 2 years)
timeFrame: 2 years
measure: Duration of the treatment-free period (second year)
timeFrame: 2 years
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: Department of Internal Medicine II and Department of Ophthalmology
Study officials:
affiliation: Tuebingen University Hospital
name: Ina Koetter, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kotter I, Gunaydin I, Zierhut M, Stubiger N. The use of interferon alpha in Behcet disease: review of the literature. Semin Arthritis Rheum. 2004 Apr;33(5):320-35. doi: 10.1016/j.semarthrit.2003.09.010.
citation: Kotter I, Vonthein R, Zierhut M, Eckstein AK, Ness T, Gunaydin I, Grimbacher B, Blaschke S, Peter HH, Stubiger N. Differential efficacy of human recombinant interferon-alpha2a on ocular and extraocular manifestations of Behcet disease: results of an open 4-center trial. Semin Arthritis Rheum. 2004 Apr;33(5):311-9. doi: 10.1016/j.semarthrit.2003.09.005.
citation: Kotter I, Zierhut M, Eckstein AK, Vonthein R, Ness T, Gunaydin I, Grimbacher B, Blaschke S, Meyer-Riemann W, Peter HH, Stubiger N. Human recombinant interferon alfa-2a for the treatment of Behcet's disease with sight threatening posterior or panuveitis. Br J Ophthalmol. 2003 Apr;87(4):423-31. doi: 10.1136/bjo.87.4.423.
citation: Stuebiger N, Koetter I, Zierhut M. Complete regression of retinal neovascularization after therapy with interferon alfa in Behcet's disease. Br J Ophthalmol. 2000 Dec;84(12):1437-8. doi: 10.1136/bjo.84.12.1432g. No abstract available.
citation: Kotter I, Aepinus C, Graepler F, Gartner V, Eckstein AK, Stubiger N, Kaskas B, Zierhut M, Bultmann B, Kandolf R, Kanz L. HHV8 associated Kaposi's sarcoma during triple immunosuppressive treatment with cyclosporin A, azathioprine, and prednisolone for ocular Behcet's disease and complete remission of both disorders with interferon alpha. Ann Rheum Dis. 2001 Jan;60(1):83-6. doi: 10.1136/ard.60.1.83. No abstract available.
citation: Deuter CM, Kotter I, Gunaydin I, Zierhut M, Stubiger N. [Ocular involvement in Behcet's disease: first 5-year-results for visual development after treatment with interferon alfa-2a]. Ophthalmologe. 2004 Feb;101(2):129-34. doi: 10.1007/s00347-003-0927-7. German.
citation: Kotter I, Deuter C, Stubiger N, Zierhut M. Interferon-a (IFN-a) application versus tumor necrosis factor-a antagonism for ocular Behcet's disease: focusing more on IFN. J Rheumatol. 2005 Aug;32(8):1633; author reply 1634. No abstract available.