Interferon α2a Versus Cyclosporine for Refractory Behçet's Disease Uveitis

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

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.

Study Overview

• Status: Completed
• Conditions: Uveitis; Behçet Disease
• Intervention / Treatment: Drug: Interferon Alfa-2A; Drug: Cyclosporine Pill

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interferon Alpha 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.	Drug: Interferon Alfa-2A; 3×10^6 IU， subcutaneous or intramuscular injection, qd for × 4 weeks, and qod thereafter
Active Comparator: Cyclosporine; Patients are treated with oral CsA 100mg twice daily.	Drug: Cyclosporine Pill; 100mg， oral, bid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2017
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): January 31, 2021

Study Registration Dates

• First Submitted: July 4, 2017
• First Submitted That Met QC Criteria: July 5, 2017
• First Posted (Actual): July 6, 2017

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 20, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: effectiveness, safety
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Behcet Syndrome; Uveitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Interferons; Interferon-alpha; Interferon alpha-2; Cyclosporine; Cyclosporins
• Other Study ID Numbers: Z171100001017217

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The individual participant data are available from the investigator upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No