Clinical trial NCT01015547: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Juvenile Idiopathic Arthritis
Keywords: juvenile idiopathic arthritis
polyarthritis
combination therapy
biologic agents
TNF antagonists
infliximab
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Foundation for Paediatric Research, Finland
name: Päivikki and Sakari Sohlberg Foundation, Finland
name: Rheumatism Foundation Hospital
name: Scandinavian Rheumatology Research Foundation
name: Paijat-Hame Hospital District
First posted: 2009-11-18
Enrollment: 60
Sex: ALL
Minimum age (years): 4
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: ACR Pedi 75 response
timeFrame: 54 weeks from baseline (0)
Secondary outcomes:
measure: clinically inactive disease
timeFrame: at 54 weeks
measure: time spent in inactive disease
timeFrame: 0 to 54 weeks
measure: time spent in ACR Pedi 75
timeFrame: 0 to 54 weeks
measure: Other ACR Pedi responses (30, 50, 70, 90, 100)
timeFrame: 0 to 54 weeks
measure: drug survival
timeFrame: 54 weeks
measure: occurrence of side-effects and adverse events
timeFrame: 0 to 54 weeks
measure: cost-benefit ratio in each treatment arm
timeFrame: 0 to 54 weeks
Other outcomes:
Locations:
city: Heinola
country: Finland
facility: Rheumatism Foundation Hospital
city: Helsinki
country: Finland
facility: Hospital for Children and Adolescents
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Oulu
country: Finland
facility: Oulu University Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
Study officials:
affiliation: Hospital for Children and Adolescents in Helsinki University Central Hospital
name: Pekka Lahdenne, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Lahdenne P, Vahasalo P, Honkanen V. Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann Rheum Dis. 2003 Mar;62(3):245-7. doi: 10.1136/ard.62.3.245.
citation: Tynjala P, Vahasalo P, Tarkiainen M, Kroger L, Aalto K, Malin M, Putto-Laurila A, Honkanen V, Lahdenne P. Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial. Ann Rheum Dis. 2011 Sep;70(9):1605-12. doi: 10.1136/ard.2010.143347. Epub 2011 May 28.
citation: Tarkiainen M, Tynjala P, Vahasalo P, Aalto K, Kroger L, Rebane K, Lahdenne P, Martikainen J. Economic evaluation of infliximab, synthetic triple therapy and methotrexate in the treatment of newly diagnosed juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2022 Nov 16;20(1):97. doi: 10.1186/s12969-022-00748-w.
citation: Tarkiainen M, Tynjala P, Vahasalo P, Kroger L, Aalto K, Lahdenne P. Health-related quality of life during early aggressive treatment in patients with polyarticular juvenile idiopathic arthritis: results from randomized controlled trial. Pediatr Rheumatol Online J. 2019 Dec 16;17(1):80. doi: 10.1186/s12969-019-0370-1.