Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis

Official Title: “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.”

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Infliximab plus methotrexate
  • 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.
• Drug: Combination 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.
• Drug: Methotrexate 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 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.
• Experimental: 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.
• Active Comparator: 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.

Primary Measures

• ACR Pedi 75 response
  • Time Frame: 54 weeks from baseline (0)
    Safety Issue?: No

Secondary Measures

• clinically inactive disease
  • Time Frame: at 54 weeks
    Safety Issue?: No
• time spent in inactive disease
  • Time Frame: 0 to 54 weeks
    Safety Issue?: No
• time spent in ACR Pedi 75
  • Time Frame: 0 to 54 weeks
    Safety Issue?: No
• Other ACR Pedi responses (30, 50, 70, 90, 100)
  • Time Frame: 0 to 54 weeks
    Safety Issue?: No
• drug survival
  • Time Frame: 54 weeks
    Safety Issue?: No
• occurrence of side-effects and adverse events
  • Time Frame: 0 to 54 weeks
    Safety Issue?: Yes
• cost-benefit ratio in each treatment arm
  • Time Frame: 0 to 54 weeks
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 4 Years

Maximum Age for this Clinical Trial: 15 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Helsinki University Central Hospital Other

Overall Clinical Trial Officials and Contacts

Pekka Lahdenne, MD, PhD Study Director Hospital for Children and Adolescents in Helsinki University Central Hospital  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01015547

Study ID Number: 211864, 318/E0/2002

ClinicalTrials.gov Identifier: NCT01015547

Health Authority: Finland: Finnish Medicines Agency

Registry of Clinical Trials in Helsinki University Central Hospital

Finnish Medical Agency