Tocilizumab for the Treatment of Refractory Behcet's Uveitis

Study Overview
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Brief Summary
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The aim of this single-center prospective study is to evaluate the efficacy and safety of Tocilizumab (TCZ), humanized monoclonal antibody against IL-6receptor, in the treatment of refractory Uveitis of Behçet's disease (BDU), to verify its effects on decreasing the dose of cortical steroids, and to determine whether it can reduce BDU recurrence.

Detailed Description
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Uveitis of Behçet's disease (BDU) is the most common form of ocular manifestations, which is also the leading cause of irreversible visual impairment. The aim of the study is to Improve treatment strategy of the disease as well as to reduce blindness. Tocilizumab (TCZ) is a humanized antibody against IL-6 receptor, clinical trials on non-infectious uveitis and retrospective study on BDU has obtained expected results. This single-center prospective study is to evaluate the efficacy and safety of TCZ in the treatment of refractory BDU, to verify its effects on decreasing the dose of corticosteroids, and to determine whether it can reduce BDU recurrence.The investigators aim to enroll nine refractory BDU patients with acute onset uveitis, with difficulty tapering corticosteroids while being treated with at least one of the commonly used immunosuppressants. All participants will receive TCZ , oral corticosteroids and immunosuppressants will remain unchanged, intraocular injection will be avoided. During monthly follow-up, the investigators will measure and record intraocular inflammation status，as well as extraocular manifestations and the acute-phase reactants. The participants will continue to receive TCZ for six months, the primary end point is the efficacy four weeks after first dose of TCZ, secondary end points other than intraocular inflammation will be achieved on each follow-up visit, as quality of life improvements, side effects, recurrence of uveitis, and corticosteroids-tapering effects. On statistical analysis, the self-control treatment efficiency and recurrence rate difference will be determined using T-test of paired samples at a significance level of 0.05(2-sided). To ensure the interest of the participants, the study has been reviewed by the PUMCH ethics committee, and drug clinical research liability insurance was prepared.

Official Title
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Efficacy and Safety of Tocilizumab in the Treatment of Refractory Uveitis in Patients With Behcet's Disease

Conditions
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Behcet Syndrome, Uveitis

Intervention / Treatment
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* Biological: Tocilizumab (TCZ)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants fulfill the the proposed International Criteria for BD, either ISG criteria(1990) or ICBD criteria(2013). All participants present with refractory BDU , acute onset uveitis, either posterior segment involvement or panuveitis, with difficulty tapering corticosteroids while being treated with at least one of the commonly used immunosuppressants, without severe extraocular manifestations. Exclusion Criteria: Patients with impaired hepatic and renal function, other severe ocular diseases, active tuberculosis, viral hepatitis, malignancy, pregnancy will be excluded.

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
Intervention Model: Single Group Assignment
Interventional Model Description: Tocilizumab is approved for the treatment of several inflammatory disease, this study tends to evaluate the response to TCZ in refractory BDU, thus it is a self-control study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocilizumab for refractory BDU<br>This study is a self-control study and all the participants will be enrolled in the interventional arm. | Biological: Tocilizumab (TCZ)<br>* Patients with refractory BD associated uveitis will receive Tocilizumab therapy, the efficacy and corticosteroids-tapering effects will be evaluated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Tocilizumab on BD Uveitis | Remission or deterioration of uveitis，based on intraocular inflammation evaluation | four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular inflammation evaluation BOS24 index | Visual acuity, anterior chamber cells, vitreous opacities, retinal inflammation, macular thickness, etc. | each follow-up visit / every four weeks, up to six months | 
| Corticosteroid-tapering effects | Whether corticosteroid dosage could be tapered to minimum dose. | six months | 
| Reduction of uveitis recurrence | Differences of recurrence between before and after treatment | each follow-up visit / every four weeks, up to six months | 
| Severity of uveitis on recurrence | Differences of severity of recurrence between before and after treatment | each follow-up visit / every four weeks, up to six months | 
| Improvement of quality of life | Record quality of life on questionnaire: BDCAF | each follow-up visit / every four weeks, up to six months | 
| Improvement of quality of life | Record quality of life on questionnaire: SF-36 | each follow-up visit / every four weeks, up to six months | 
| Side effects of treatment | Record any side effects during intervention | each follow-up visit / every four weeks, up to six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tocilizumab, Refractory uveitis