Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial.

Abstract

OBJECTIVES:

In juvenile idiopathic arthritis (JIA), the efficacy of very early disease-modifying drug therapy, synthetic or biological, is not well known. Three alternative strategies were compared for treating recent-onset polyarticular JIA.

METHODS:

In a 54-week multicentre open-label clinical trial, 60 disease-modifying antirheumatic drug (DMARD)-naive patients aged 4-15 years were randomly assigned into three treatment arms. The efficacy of infliximab plus methotrexate (TNF) was compared to that of two synthetic therapies: methotrexate alone (MTX) and DMARD methotrexate, sulphasalazine and hydroxychloroquine in combination (COMBO). Primary endpoint was American College of Rheumatology paediatric 75% improvement (ACR Pedi 75). Secondary endpoints were inactive disease and safety.

RESULTS:

In 59 patients, mean (±SE) age at baseline was 9.6±0.4 years, duration of JIA 1.9±0.2 months and number of active joints 18±1. ACR Pedi 75 was achieved in 100% (19/19) of patients receiving TNF, 65% (13/20) on COMBO (95% CI 44% to 86%) and 50% (10/20) on methotrexate (95% CI 28% to 72%) p<0.0001. Thirteen patients receiving TNF (68%; 95% CI 47% to 89%) achieved inactive disease, whereas eight (40%; 95% CI 22% to 63%) on COMBO and five (25%; 95% CI 6% to 44%) on methotrexate did (p=0.002). Patients on TNF spent a mean 26 weeks (95% CI 18 to 34) with inactive disease, longer than did those receiving COMBO (13 weeks; 95% CI 6 to 20), or methotrexate (6 weeks; 95% CI 2 to 10). Serious adverse events were rare.

CONCLUSION:

In early polyarticular JIA, targeting to achieve minimally active or inactive disease, infliximab plus methotrexate was superior to synthetic DMARD in combination and strikingly superior to methotrexate alone.

• Authors: Pirjo Tynjälä, Paula Vähäsalo, Maarit Tarkiainen, Liisa Kröger, Kristiina Aalto, Merja Malin, Anne Putto-Laurila, Visa Honkanen, Pekka Lahdenne
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 70 Issue 9 Pg. 1605-12 (Sep 2011) ISSN: 1468-2060 [Electronic] England
• PMID: 21623000 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antirheumatic Agents
• Drug Combinations
• Glucocorticoids
• Tumor Necrosis Factor-alpha
• Sulfasalazine
• Hydroxychloroquine
• Infliximab
• Methotrexate

Topics

• Adolescent
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antirheumatic Agents (adverse effects, therapeutic use)
• Arthritis, Juvenile (drug therapy)
• Child
• Child, Preschool
• Drug Combinations
• Epidemiologic Methods
• Female
• Glucocorticoids (administration & dosage)
• Humans
• Hydroxychloroquine (adverse effects, therapeutic use)
• Infliximab
• Injections, Intra-Articular
• Male
• Methotrexate (adverse effects, therapeutic use)
• Sulfasalazine (adverse effects, therapeutic use)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)