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.
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 60
- Locations
- 6
- Primary Endpoint
- ACR Pedi 75 response
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 4 Years to 15 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Infliximab plus Methotrexate
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.
Intervention: Infliximab plus methotrexate (Drug)
Combination of DMARDs
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.
Intervention: Combination of DMARDs (Drug)
Methotrexate alone
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.
Intervention: Methotrexate alone (Drug)
Outcomes
Primary Outcomes
ACR Pedi 75 response
Time Frame: 54 weeks from baseline (0)
Secondary Outcomes
- time spent in inactive disease(0 to 54 weeks)
- cost-benefit ratio in each treatment arm(0 to 54 weeks)
- drug survival(54 weeks)
- occurrence of side-effects and adverse events(0 to 54 weeks)
- clinically inactive disease(at 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)
Investigators
Pirjo Tynjala
MD PhD
Helsinki University Central Hospital