Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE-JIA)

Helsinki University Central Hospital (HUCH)

Status and phase: Completed; Phase 3

Conditions: Juvenile Idiopathic Arthritis

Treatments: Drug: Methotrexate alone; Drug: Infliximab plus methotrexate; Drug: Combination of DMARDs

Study type: Interventional

Funder types: Other

Identifiers

NCT01015547

211864, 318/E0/2002

211864 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 4 to 15 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

Infliximab plus Methotrexate

Experimental group

Description:

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.

Treatment:

Drug: Infliximab plus methotrexate

Combination of DMARDs

Experimental group

Description:

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.

Treatment:

Drug: Combination of DMARDs

Methotrexate alone

Active Comparator group

Description:

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.

Treatment:

Drug: Methotrexate alone