A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis.

Abstract

OBJECTIVE:

To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA).

METHODS:

This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate (MTX) therapy were randomized to receive infliximab or placebo for 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44.

RESULTS:

Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose.

CONCLUSION:

While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.

• Authors: Nicolino Ruperto, Daniel J Lovell, Ruben Cuttica, Nick Wilkinson, Patricia Woo, Graciela Espada, Carine Wouters, Earl D Silverman, Zsolt Balogh, Michael Henrickson, Maria-Teresa Apaz, Eileen Baildam, Anders Fasth, Valeria Gerloni, Pekka Lahdenne, Anne-Marie Prieur, Angelo Ravelli, Rotraud K Saurenmann, Maria Luz Gamir, Nico Wulffraat, Laszlo Marodi, Ross E Petty, Rik Joos, Francesco Zulian, Deborah McCurdy, Barry L Myones, Kalman Nagy, Peter Reuman, Ilona Szer, Suzanne Travers, Anna Beutler, Greg Keenan, Jason Clark, Sudha Visvanathan, Adedigbo Fasanmade, Aparna Raychaudhuri, Alan Mendelsohn, Alberto Martini, Edward H Giannini, Paediatric Rheumatology International Trials Organisation, Pediatric Rheumatology Collaborative Study Group
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 56 Issue 9 Pg. 3096-106 (Sep 2007) ISSN: 0004-3591 [Print] United States
• PMID: 17763439 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antirheumatic Agents
• Infliximab
• Methotrexate

Topics

• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antirheumatic Agents (administration & dosage, adverse effects)
• Arthritis, Juvenile (drug therapy)
• Child
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Infliximab
• Male
• Methotrexate (administration & dosage, adverse effects)