Interferon α2a Versus Cyclosporine for Refractory Behçet's Disease Uveitis

Phase 3

Completed

• Conditions: Behçet Disease; Uveitis
• Interventions: Drug: Cyclosporine Pill; Drug: Interferon Alfa-2A

• Registration Number: NCT03209219
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-06-30
• Study First Submitted: 2017-07-04
• Study First Submitted QC: 2017-07-05
• Study First Posted: 2017-07-06
• Primary Completion: 2020-08-31
• Study Completion: 2021-01-31
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-20
• Last Update Posted: 2021-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyclosporine	Cyclosporine Pill	Patients are treated with oral CsA 100mg twice daily.
Interferon Alpha 2A	Interferon Alfa-2A	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Peking Union Medical College; 🇨🇳 Beijing, Beijing, China