Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis

Study Overview
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Brief Summary
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This study is a multi-center randomized non-inferiority study that aims to observe the short-term (3 months) efficacy and safety of adalimumab plus medium-dose glucocorticosteroid (30mg/d prednisone or equivalent) with slow tapering for recurrent Behçet's uveitis (BU) attack compared with adalimumab plus high-dose glucocorticosteroid (60mg/d prednisone or equivalent) with slow tapering.

Detailed Description
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According to the most recent European League Against Rheumatism (EULAR) recommendation, patients presenting with an initial or recurrent episode of acute sight-threatening uveitis should be treated with high-dose glucocorticoids, infliximab or interferon-α. Adalimumab, another TNFα antagonist, is also considered as an alternative for infliximab and have proved its efficacy in several RCTs in the treatment of non-infectious intermediate, posterior and pan-uveitis. As higher dose glucocorticosteroid have greater side effects, this study aims to evaluate the non-inferior efficacy and safety of adalimumab plus medium-dose glucocorticosteroid compared with adalimumab plus high-dose glucocorticosteroid (and slow tapering) for recurrent posterior or pan-uveitis attack of Behcet's uveitis. Refractory BU is defined as relapse of posterior or panuveitis with at least 10mg daily prednisone (or equivalent). The acute attack will be controlled with adalimumab (80mg once, 40mg q2w thereafter) plus medium dose initial oral glucocorticosteroid (30mg daily prednisone or equivalent) in the medium dose group or plus high dose oral glucocorticosteroid (60mg daily prednisone or equivalent) in the high dose group with fixed tapering protocols. Patients will be followed up at 2w, 4w, 8w, and 12w after initiation of treatment. The primary endpoint is the inflammatory control rate. Secondary endpoints are BCVA, vascular leakage score on fundus fluorescein angiography (FFA), BOS 24 score and uveitis deterioration rate. The safety profiles of both groups will be also monitored.

Official Title
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Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis, Compared With Adalimumab Plus High Dose Oral Glucocorticosteroid, a Non-inferior, Multi-center, Randomized Controlled Trial.

Conditions
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Uveitis

Intervention / Treatment
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* Drug: Adalimumab plus different doses of oral glucocorticosteroid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Behçet's disease (BD) 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 Exclusion Criteria: Previous treatment with TNFα inhibitors within 3 months Pregnancy, breast feeding women Malignancy Heart failure Demyelinating diseases Renal impairment (creatinine > 1.5 mg/dl) 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 intermediate dose corticosteroids 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: Medium dose group (Adalimumab plus medium dose oral glucocorticosteroid)<br>Patients will be given adalimumab with 30mg daily prednisone or equivalent with a fixed slow tapering plan. | Drug: Adalimumab plus different doses of oral glucocorticosteroid<br>* A loading dose of 80mg adalimumab will be given subcutaneously and then change to 40mg adalimumab every two weeks. Medium dose oral glucocorticosteroid (30mg/d prednisone or equivalent) will be given to the experimental dose group and high dose oral glucocorticosteroid (60mg/d prednisone or equivalent) will be given to the high dose group.<br>* Other names: Humira, prednisone;|
| Active Comparator: High dose group (Adalimumab plus high dose oral glucocorticosteroid)<br>Patients will be given adalimumab with 60mg daily prednisone or equivalent with a fixed slow tapering plan. | Drug: Adalimumab plus different doses of oral glucocorticosteroid<br>* A loading dose of 80mg adalimumab will be given subcutaneously and then change to 40mg adalimumab every two weeks. Medium dose oral glucocorticosteroid (30mg/d prednisone or equivalent) will be given to the experimental dose group and high dose oral glucocorticosteroid (60mg/d prednisone or equivalent) will be given to the high dose group.<br>* Other names: Humira, prednisone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uveitis control | Inflammation control according to SUN criteria (two steps decrease of anterior chamber cell or vitreous haze or decreased to zero) or active retinal lesion recession with vitreous haze less than 0.5 grade | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best corrected visual acuity (BCVA) | BCVA was transformed into logMar form | 3 months | 
| Extent of vascular leakage | Vascular leakage was quantified based on the method developed by the Angiography Scoring for Uveitis Working Group (ASUWOG), in which vascular leakage in the posterior pole and in each peripheral quadrant was scored 1 if limited | 3 months | 
| BOS 24 score | BOS 24 scoring system refers to article Behc et's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab | 3 months | 
| Uveitis deterioration | Inflammation deterioration according to SUN criteria (two steps increase of anterior chamber cell or vitreous haze or increases to grade 4) or new active retinal lesions or new onset of retinal vasculitis | 3 months |