Childhood Arthritis

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

  1. Nicolino Ruperto1,‡,*,
  2. Daniel J. Lovell2,‡,
  3. Ruben Cuttica3,
  4. Nick Wilkinson4,
  5. Patricia Woo5,
  6. Graciela Espada6,
  7. Carine Wouters7,
  8. Earl D. Silverman8,
  9. Zsolt Balogh9,
  10. Michael Henrickson10,
  11. Maria-Teresa Apaz11,
  12. Eileen Baildam12,
  13. Anders Fasth13,
  14. Valeria Gerloni14,
  15. Pekka Lahdenne15,
  16. Anne-Marie Prieur16,
  17. Angelo Ravelli17,
  18. Rotraud K. Saurenmann18,‡,
  19. Maria Luz Gamir19,
  20. Nico Wulffraat20,
  21. Laszlo Marodi21,
  22. Ross E. Petty22,
  23. Rik Joos23,
  24. Francesco Zulian24,
  25. Deborah McCurdy25,
  26. Barry L. Myones26,
  27. Kalman Nagy27,
  28. Peter Reuman28,
  29. Ilona Szer29,
  30. Suzanne Travers30,‡,
  31. Anna Beutler30,‡,
  32. Greg Keenan30,‡,
  33. Jason Clark30,‡,
  34. Sudha Visvanathan30,‡,
  35. Adedigbo Fasanmade30,‡,
  36. Aparna Raychaudhuri30,‡,
  37. Alan Mendelsohn30,‡,
  38. Alberto Martini17,
  39. Edward H. Giannini2

Article first published online: 30 AUG 2007

DOI: 10.1002/art.22838

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 56, Issue 9, pages 3096–3106, September 2007

Additional Information

How to Cite

Ruperto, N., Lovell, D. J., Cuttica, R., Wilkinson, N., Woo, P., Espada, G., Wouters, C., Silverman, E. D., Balogh, Z., Henrickson, M., Apaz, M.-T., Baildam, E., Fasth, A., Gerloni, V., Lahdenne, P., Prieur, A.-M., Ravelli, A., Saurenmann, R. K., Gamir, M. L., Wulffraat, N., Marodi, L., Petty, R. E., Joos, R., Zulian, F., McCurdy, D., Myones, B. L., Nagy, K., Reuman, P., Szer, I., Travers, S., Beutler, A., Keenan, G., Clark, J., Visvanathan, S., Fasanmade, A., Raychaudhuri, A., Mendelsohn, A., Martini, A. and Giannini, E. H. (2007), A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis & Rheumatism, 56: 3096–3106. doi: 10.1002/art.22838

Author Information

  1. 1

    IRCCS, Istituto G. Gaslini, Genoa, Italy

  2. 2

    Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

  3. 3

    Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina

  4. 4

    Nuffield Orthopaedic Centre, Oxford, UK

  5. 5

    Great Ormond Street Hospital, London, UK

  6. 6

    Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

  7. 7

    University Hospital Gasthuisberg, Leuven, Belgium

  8. 8

    Hospital for Sick Children, Toronto, Ontario, Canada

  9. 9

    National Institute of Rheumatology and Physiotherapy, Budapest, Hungary

  10. 10

    Children's Hospital, Oklahoma City, Oklahoma

  11. 11

    Universidad Catolica, Cordoba, Argentina

  12. 12

    Royal Liverpool Children's Hospital, Liverpool, UK

  13. 13

    Queen Silvia Children's Hospital, Goteborg, Sweden

  14. 14

    Istituto Gaetano Pini, Milan, Italy

  15. 15

    Hospital for Children and Adolescents, Helsinki, Finland

  16. 16

    Hôpital Necker Enfants Malades, Paris, France

  17. 17

    IRCCS, Istituto G. Gaslini, and University of Genoa, Genoa, Italy

  18. 18

    Kinderspital Zurich, Zurich, Switzerland

  19. 19

    Hospital Ramón y Cajal, Madrid, Spain

  20. 20

    Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands

  21. 21

    University of Debrecen, Debrecen, Hungary

  22. 22

    University of British Columbia, Vancouver, British Columbia, Canada

  23. 23

    Universitair Ziekenhuis Ghent, Ghent, Belgium

  24. 24

    Clinica Pediatrica, Padua, Italy

  25. 25

    Children's Hospital of Orange County, Orange, California

  26. 26

    Texas Children's Hospital Pediatric Rheumatology Center, Houston

  27. 27

    Borsod University Hospital, Miskolc, Hungary

  28. 28

    Children's Hospital Medical Center, Akron, Ohio

  29. 29

    Children's Hospital Medical Center, San Diego, California

  30. 30

    Centocor, Inc., Malvern, Pennsylvania

  1. ‡

    Drs. Ruperto, Lovell, Woo, Prieur, Petty, Martini, and Giannini have received honoraria and/or consulting fees (less than $10,000) from Centocor for serving as members of the study steering committee. Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Hoffmann-LaRoche, Amgen, Novartis, Bristol-Myers Squibb, Abbott, and Xoma and (more than $10,000) from Regeneron. Dr. Saurenmann has received honoraria (less than $10,000) from Essex for serving as a member of the Remicade “Switzerland” advisory board. Drs. Travers, Beutler, Keenan, Clark, Visvanathan, Fasanmade, Raychaudhuri, and Mendelsohn own stock or stock options in Johnson & Johnson, of which Centocor, Inc., is a subsidiary.

*IRCCS, Istituto G. Gaslini, Pediatria II–PRINTO, Largo Gaslini 5, 16147 Genoa, Italy

  1. †

    ClinicalTrials.gov identifier: NCT00036374.

  2. ‡

    Drs. Ruperto, Lovell, Woo, Prieur, Petty, Martini, and Giannini have received honoraria and/or consulting fees (less than $10,000) from Centocor for serving as members of the study steering committee. Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Hoffmann-LaRoche, Amgen, Novartis, Bristol-Myers Squibb, Abbott, and Xoma and (more than $10,000) from Regeneron. Dr. Saurenmann has received honoraria (less than $10,000) from Essex for serving as a member of the Remicade “Switzerland” advisory board. Drs. Travers, Beutler, Keenan, Clark, Visvanathan, Fasanmade, Raychaudhuri, and Mendelsohn own stock or stock options in Johnson & Johnson, of which Centocor, Inc., is a subsidiary.

Publication History

  1. Issue published online: 30 AUG 2007
  2. Article first published online: 30 AUG 2007
  3. Manuscript Accepted: 16 MAY 2007
  4. Manuscript Received: 25 OCT 2006

Funded by

  • Centocor, Inc.

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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.

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