The Efficacy and Safety of Adalimumab in Non-infectious Anterior Pediatric Uveitis With Peripheral Vascular Leakage

Study Overview
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Brief Summary
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Children with anterior uveitis are prone to suffer from chronic recurrent course of intraocular inflammation and adverse effects of glucocorticosteroids (GCs) /immunomodulatory treatment (IMT) agents. The performance of adalimumab has been shown to be fairly favorable in treating refractory non-infectious uveitis. This study aims to assess the efficacy and safety of adalimumab for inflammatory flare prevention in non-infectious anterior pediatric uveitis with peripheral vascular leakage compared with methotrexate. Children weighed ≥ 30kg and aged between 4-16 years old with active chronic non-infectious anterior uveitis with peripheral retinal vascular leakage on ultra wildfield fluorescence fundus angiography (UWFFA) will be included. They will be treated with a predesigned inflammatory control regimen to reach inflammatory quiescence in 1 month. After that they will be treated with either MTX or adalimumab and regularly followed up for at least 6 months. The primary endpoint is treatment failure defined as any inflammatory fare with anterior chamber cell count grading increased from 0 to 1. Secondary endpoints are best corrected visual acuity (BCVA), inflammation parameters (keratic precipitates, vitreous haze grades), extent of vascular leakage, frequency of topical steroid eyedrops, systemic immunosuppressive drug load, and adverse events.

Detailed Description
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This is a prospective, single-center, interventional, randomized, non-blinded, controlled clinical trial that will be performed at the Ophthalmology Department, Peking Union Medical College Hospital. Children with active noninfectious anterior uveitis demonstrating peripheral vascular leakage on UWFFA and meet the selection criteria will be randomly assigned to treatment group or control group. Both groups will be treated with a predesigned plan for the active inflammation. At one month or when patients' ocular inflammation gets controlled to 0.5+ cell in the anterior chamber, whichever comes later, patients in the treatment group will be given adalimumab subcutaneously at 40mg every 2 weeks, patients in the control group will be given methotrexate10mg orally once a week. Follow-up visits will be scheduled every two weeks at the run-in period and the first month after randomization, and every month from the second to the sixth month. The primary endpoint is treatment failure defined as any inflammatory fare with anterior chamber cell count grading increased from 0 to 1. Secondary endpoints are best corrected visual acuity (BCVA), inflammation parameters (keratic precipitates, vitreous haze grades), extent of vascular leakage, frequency of topical steroid eyedrops, systemic immunosuppressive drug load, and adverse events.

Official Title
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The Efficacy and Safety of Adalimumab for Inflammatory Flare Prevention in Non-infectious Anterior Pediatric Uveitis With Peripheral Vascular Leakage Compared With Methotrexate, a RCT Study

Conditions
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Uveitis, Anterior, Adalimumab

Intervention / Treatment
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* Drug: Adalimumab
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with noninfectious uveitis aged between 4-16, weight ≥ 30kg. Uveitis resistant to well conducted topical steroid therapy for three months, or uveitis resistant to well conducted 0.1% prednisolone twice a day for one month Retina peripheral vascular leakage demonstrated by UWFFA at the time of inclusion. Exclusion Criteria: Any contraindication to administration of immunosuppressive therapy (active tuberculosis, immune deficit, opportunistic infection, other severe chronic disease). Previous diagnosis or signs of demyelinating disease of the central nervous system. Children unable to cooperate with examinations and follow-up. Positive allergy skin test when conducting fluorescence fundus angiography. Diffuse vascular leakage, macula edema or any retina lesions demonstrated by UWFFA. History of oral immunosuppressive drug treatment within 2 months History of biological treatment within 2 months History of triamcinolone acetonide subconjunctival/intraocular injection within 3 months Current topical steroid use more than six times per day History of eye surgery within 3 months. Eye complications that interfere with fundus observation.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 16 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective, single-center,open-lablel, interventional, randomizedcontrolled clinical trial that will be performed at the Ophthalmology Department, Peking Union Medical College Hospital.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab<br>Adalimumab administered subcutaneously at 40mg every 2 weeks | Drug: Adalimumab<br>* ADA 40mg q2w<br>* Other names: ADA;|
| Active Comparator: Methotrexate<br>Methotrexate given 10mg orally once a week. | Drug: Methotrexate<br>* MTX 10mg qw<br>* Other names: MTX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uveitis flare | Uveitis flare is defined as anterior chamber cell count grading increased from 0 to 1. The grading method is in accordance with SUN criteria. Anterior chamber cell count was scored according to Standardization of Uveitis Nomenclature (SUN) criteria | At 6 months' follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of peripheral 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 and scored 2 if diffuse. Total maximum score will 8 since leakage in the posterior pole will be excluded in this study. | At 6 months' follow-up visit | 
| Keratic precipitates | Keratic precipitates was recorded in a dichotomous method. | At 6 months' follow-up visit | 
| Vitreous haze | Vitreous haze will graded as the same method of anterior chamber cell, the slit lamp will be pushed forward to the vitreous to observe vitreous haze. | At 6 months' follow-up visit | 
| Best corrected visual acuity (BCVA) | BCVA was transformed into logMar form | At 6 months' follow-up visit | 
| Adverse events | Adverse events included the infectious events and laboratory parameter abnormalities. | through study completion, an average of 6 months | 
| frequency of topical steroid eyedrops if any inflammatory flare happens. | Different GCs eye drops are transformed into equivalent 1% prednisolone for analysis. | At 6 months' follow-up visit | 
| Systemic immunomodulatory therapy (sIMT, including GCs and immunosuppressive drugs)load at the 6-month follow-up visit if any inflammatory flare ever happens. | sIMT load is transformed into a quantizable score based on prior studies in uveitis. | At 6 months' follow-up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pheripheral retinal vasuclar leakage, adalimumab, methotrexate