Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis

Study Overview
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Brief Summary
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The objective of this study is to compare in very early polyarticular juvenile idiopathic arthritis (JIA) the efficacy, safety, and cost-benefit-ratio of three treatment strategies: biologic combination, combination of conventional disease-modifying drugs (DMARDs), and methotrexate alone.

Detailed Description
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DMARD-naive polyarticular JIA patients with an early disease (onset less than 6 months) are randomized into one of three treatment strategies: (1) biological combination, i.e., anti-TNF therapy with infliximab plus methotrexate; (2) Combination of DMARDs with methotrexate, sulfasalazine, plus hydroxychloroquine; and (3) Methotrexate alone. The efficacy is evaluated by American College of Rheumatology Pediatric (ACR Pedi) criteria based on 6 core set variables (CSVs): 1. no of active joints; 2. no. of joints with pain or tenderness and limitation of motion; 3. ESR (mm/hr); 4. the Childhood Health Assessment Questionnaire (CHAQ); 5. Physician's Visual Analogue Scale (VAS); 6. Patient/Parent VAS. To fulfill ACR Pedi 75 criteria, 3/6 CSVs have to improve 75% and not more than 1/6 CSV worsen more than 30%. All direct and indirect costs are documented. The first phase of the study is open-label clinical trial lasting for 54 weeks. In the second phase of the study the patients are followed up to 5 years, and the long-term outcome of early aggressive therapy is analyzed. Serum, urine, and saliva samples are collected at 3 and 5 years for translational research.

Official Title
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Comparison of Anti-TNF Therapy Plus Methotrexate, Combination Therapy of DMARDs, and Methotrexate Alone in Very Early Polyarticular Juvenile Idiopathic Arthritis. A National Randomized Multicenter Clinical Trial.

Conditions
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Juvenile Idiopathic Arthritis

Intervention / Treatment
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* Drug: Infliximab plus methotrexate
* Drug: Combination of DMARDs
* Drug: Methotrexate alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: juvenile idiopathic arthritis arthritis lasting for at least 6 weeks but not more than 6 months polyarticular disease with at least 5 active joints with at least 3 joints with pain or tenderness and limitation of motion no previous treatment with DMARDs Exclusion Criteria: systemic JIA any abnormality in the hematopoietic or lymphatic system any major concurrent medical condition inadequate psychosocial situation pregnancy a non-abstinent female with reproductive capacity without regular contraceptive use

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 15 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: Infliximab plus Methotrexate<br>infliximab 3-5 mg/kg every 6 weeks, plus methotrexate 15 mg/m2 weekly given orally (dose escalation if ACR Pedi less than 75). no oral prednisolone. intra-articular steroids allowed. | Drug: Infliximab plus methotrexate<br>* IFX given 3-5mg/kg every 6 weeks, oral MTX given 15mg/m2 weekly. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.<br>* Other names: IFX: Remicade, MTX: Trexan or Methotrexate;|
| Experimental: Combination of DMARDs<br>methotrexate 15mg/m2 weekly given orally (dose escalation and parenteral injection if ACR Pedi less than 75), plus standard doses of sulfasalazine and hydroxychloroquine. no oral prednisolone. intra-articular steroids allowed. | Drug: Combination of DMARDs<br>* IFX given 3-5mg/kg every 6 weeks, oral MTX given 15mg/m2 weekly, SSZ 40mg/kg up to 2000mg daily, HCQ 5mg/kg daily. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.<br>* Other names: MTX: Trexan or Methotrexate, SSZ: Salazopyrin, HCQ: Oxiklorin;|
| Active Comparator: Methotrexate alone<br>Conventional drug therapy: methotrexate 15mg/m2 weekly given orally (dose escalation and parenteral injection if ACR Pedi less than 75). no oral prednisolone. intra-articular steroids allowed. | Drug: Methotrexate alone<br>* Oral MTX given 15mg/m2 weekly. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.<br>* Other names: MTX: Trexan or Methotrexate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR Pedi 75 response |  | 54 weeks from baseline (0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinically inactive disease |  | at 54 weeks | 
| time spent in inactive disease |  | 0 to 54 weeks | 
| time spent in ACR Pedi 75 |  | 0 to 54 weeks | 
| Other ACR Pedi responses (30, 50, 70, 90, 100) |  | 0 to 54 weeks | 
| drug survival |  | 54 weeks | 
| occurrence of side-effects and adverse events |  | 0 to 54 weeks | 
| cost-benefit ratio in each treatment arm |  | 0 to 54 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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juvenile idiopathic arthritis, polyarthritis, combination therapy, biologic agents, TNF antagonists, infliximab