Interferon α2a Versus Cyclosporine for Refractory Behçet's Disease Uveitis

Study Overview
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Brief Summary
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Brief summary: This study compares the long-term efficacy and safety of interferon (IFN) α2a and cyclosporine (cyclosporin A, CsA) following suppression of acute attack by high-dose oral glucocorticosteroid in patients with refractory Behçet's uveitis (BDU). Half of the participants will receive IFNα2a while the other half will receive CsA.

Detailed Description
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Detailed description: Both CsA and IFNα2a have been shown to be effective for long-term control of BDU, however, randomized prospective comparative studies are scarce, particularly in East Asian populations. Our preliminary data gave us the impression that IFNα2a might be more effectiveness than CsA in long-term control of refractory BDU, and this study aimed to compare their effectiveness and safety profiles in a well-designed prospective study. Refractory BDU is defined as relapse of posterior or pan- uveitis with at least 10mg daily prednisone (or equivalent) and one traditional immunomodulatory treatment (IMT) agents. The acute attack is controlled with large dose oral corticosteroid (60mg daily prednisone) for 4 weeks, and then the patients are randomly assigned to the IFN arm and the CsA arm, in which patients are treated with IFNα2a (3×10^6 IU qd for 4 weeks and qod thereafter) and CsA (100mg bid), respectively, along with a fixed tapering regimen of corticosteroid. Patients were followed up until relapse, or for 12 months.

Official Title
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Randomized Prospective Comparative Study of Interferon α2a and Cyclosporine in Patients With Refractory Behçet's Disease Uveitis

Conditions
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Uveitis, Behçet Disease

Intervention / Treatment
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* Drug: Interferon Alfa-2A
* Drug: Cyclosporine Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory BDU patients fulfilling the International Criteria for Behçet's disease (ICBD) published in 2013 with recent recurrence of pan- or posterior uveitis; The patient should be on ≥10mg/d oral prednisone or equivalent with at least one of the following IMT agents: cyclophosphamide≥50mg/d, CsA≥100mg/d, azathioprine≥50mg/d, methotrexate≥15mg/w, mycophenolate≥1000mg/d, tacrolimus≥2mg/d. Exclusion Criteria: Previous treatment with interferon-α; Pregnancy, breast feeding women; Malignancy; Renal impairment (creatinine > 1.5 mg/dl); Uncontrolled hypertension or diabetes; Depression or other psychic disorders; History of acute or chronic inflammatory joint or autoimmune disease; Patients with severe extra-ocular involvement other than oral/genital ulcer and skin involvement; Organ or bone marrow transplant recipient, cardiac failure > NYHA III; Acute liver disease with ALT or SGPT 2x above normal; White blood cell count < 3500/mm^3; Platelet count < 100000/mm^3; Hgb < 8.5g/dl; T-SPOT TB: ≥200 SFCs per 10^6 PBMC; Active peptic ulcer, systemic or local infection, moderate to severe osteoporosis or other contraindications of large dose corticosteroids; Previous intolerance to CsA; Other severe ocular diseases or intraocular surgery within 3 months; Media opacity precluding a clear view of the fundus; Positive screen test for HBV, HCV, HIV infection or syphilis; Body weight <45 kg; Alcohol abuse or drug abuse; Mental impairment; Uncooperative attitude.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interferon Alpha 2A<br>Patients are treated with IFNα2a 3×10^IU α2a by subcutaneous injection or intramuscular injection daily for 4 weeks, and followed by every other day there after. | Drug: Interferon Alfa-2A<br>* 3×10^6 IU， subcutaneous or intramuscular injection, qd for × 4 weeks, and qod thereafter<br>|
| Active Comparator: Cyclosporine<br>Patients are treated with oral CsA 100mg twice daily. | Drug: Cyclosporine Pill<br>* 100mg， oral, bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Percentage of participants who achieve complete remission or partial remission | Within the 12-month follow-up period | 
| Complete remission rate | Percentage of participants who achieve complete remission without relapse of posterior or pan-uveitis | Within the 12-month follow-up period | 
| Tolerance rate | Percentage of participants who adhere to the treatment without severe side effects | Within the 12-month follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach complete remission | The time from the therapy initiation to a complete absence of ocular inflammation for complete responders | Within the 12-month follow-up period | 
| Duration of relapse-free | The duration between the therapy initiation to the relapse for partial responders and nonresponders | within the 12-month follow-up period | 
| BCVA | Changes of best-corrected visual acuity | Within the 12-month follow-up period | 
| BOS24 score | Score of ocular inflammation using the Behcet disease ocular attack score 24 (BOS24) | Within the 12-month follow-up period | 
| Glucocorticoid-sparing effect | Changes of corticosteroid dosage | Within the 12-month follow-up period | 
| Incidence of adverse effects | Incidence of adverse effects | Within the 12-month follow-up period | 
| Incidence of significant abnormal changes in vital signs or laboratory test results | Incidence of significant abnormal changes in vital signs or laboratory test results | Within the 12-month follow-up period | 
| Adverse effects profile | Types of drug adverse effects | Within the 12-month follow-up period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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effectiveness, safety