Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis

Phase 3

Completed

Interventions: Drug: Infliximab plus methotrexate
Drug: Methotrexate alone
Drug: Combination of DMARDs

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Infliximab plus Methotrexate	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.
Methotrexate alone	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.
Combination of DMARDs	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.

Primary Outcome Measures

Name	Time	Method
ACR Pedi 75 response	54 weeks from baseline (0)

Secondary Outcome Measures

Name	Time	Method
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

Locations (6): Rheumatism Foundation Hospital
🇫🇮
Heinola, Finland
Hospital for Children and Adolescents
🇫🇮
Helsinki, Finland
Tampere University Hospital
🇫🇮
Tampere, Finland
Kuopio University Hospital
🇫🇮
Kuopio, Finland
Oulu University Central Hospital
🇫🇮
Oulu, Finland
Turku University Hospital
🇫🇮
Turku, Finland