Juvenile Idiopathic Arthritis
Conditions
Keywords
juvenile idiopathic arthritis, polyarthritis, combination therapy, biologic agents, TNF antagonists, infliximab
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.
Interventions
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.
DRUGCombination of DMARDs
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.
DRUGMethotrexate alone
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.
Sponsors
Foundation for Paediatric Research, Finland
Päivikki and Sakari Sohlberg Foundation, Finland
Rheumatism Foundation Hospital
Scandinavian Rheumatology Research Foundation
Paijat-Hame Hospital District
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 15 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ACR Pedi 75 response | 54 weeks from baseline (0) |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| clinically inactive disease | at 54 weeks |
| occurrence of side-effects and adverse events | 0 to 54 weeks |
| cost-benefit ratio in each treatment arm | 0 to 54 weeks |
| drug survival | 54 weeks |
Countries
Finland
Outcome results
None listed