Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis
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.
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.
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Juvenile Idiopathic Arthritis
Intervention
Infliximab plus methotrexate, Combination of DMARDs, Methotrexate alone
Location
Rheumatism Foundation Hospital
Heinola
Finland
Status
Active, not recruiting
Source
Helsinki University Central Hospital
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01015547
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Methotrexate
An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.
Tetrahydrofolate Dehydrogenase
An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.
Arthritis, Juvenile Rheumatoid
Rheumatoid arthritis of children occurring in three major subtypes defined by the symptoms present during the first six months following onset: systemic-onset (Still's Disease, Juvenile-Onset), polyarticular-onset, and pauciarticular-onset. Adult-onset cases of Still's disease (STILL'S DISEASE, ADULT-ONSET) are also known. Only one subtype of juvenile rheumatoid arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.
Drug Therapy, Combination
Therapy with two or more separate preparations given for a combined effect.
Epilepsy, Absence
A childhood seizure disorder characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736)
Clinical Trials
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Combination Methotrexate and Infliximab
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PubMed Articles
Combination systemic therapies in psoriatic arthritis.
Abstract Psoriatic arthritis (PsA) is a chronic, progressive, and debilitating disorder. When monotherapy fails, combination therapy is necessary for the long-term management of these patients. There...
ABSTRACT: BACKGROUND: We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA). METHODS: In this randomized, placebo-controlled substudy, 1...
Combination therapy using methotrexate with DMARDs or biologics - current status.
Methotrexate (MTX) is the most frequently used drug in combination treatment with disease-modifying antirheumatic drugs (DMARDs) and biologics in rheumatoid arthritis. DMARD combinations are usually t...
OBJECTIVE:: Juvenile Idiopathic Arthritis (JIA) is the most common chronic pediatric rheumatic disease and can have long-term effects leading to disability in adulthood. Biologics are a new class of d...
What is already known about the subject: - Infliximab pharmacokinetics in ankylosing spondylitis has been described but using sparce data. - A previous work suggests that infliximab concentrations inf...
