Journal Article

Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE–JIA): a multicentre randomised open-label clinical trial

Lahdenne, Pekka, Kröger, Liisa, Honkanen, Visa, Vähäsalo, Paula, Aalto, Kristiina, Tarkiainen, Maarit, Tynjälä, Pirjo, Malin, Merja, Putto-Laurila, Anne

2011

Overview

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.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,BMJ Publishing Group,Elsevier Limited
• Subject: Adolescent / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - therapeutic use / Antirheumatic Agents - adverse effects / Antirheumatic Agents - therapeutic use / Arthritis, Juvenile - drug therapy / Biological and medical sciences / Child / Child, Preschool / Clinical trials / Diseases of the osteoarticular system / Drug Combinations / Drug dosages / Drug therapy / Epidemiologic Methods / Female / Gangrene / Glucocorticoids - administration & dosage / Humans / Hydroxychloroquine - adverse effects / Hydroxychloroquine - therapeutic use / Inflammatory joint diseases / Infliximab / Injections, Intra-Articular / Male / Medical sciences / Methotrexate - adverse effects / Methotrexate - therapeutic use / Rheumatic diseases / Rheumatology / Studies / Sulfasalazine - adverse effects / Sulfasalazine - therapeutic use / TNF inhibitors / Treatment Outcome / Tumor Necrosis Factor-alpha - antagonists & inhibitors / Tumor necrosis factor-TNF