Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis

Carol A. Wallace, Edward H. Giannini, Steven J. Spalding, Philip J. Hashkes, Kathleen M. O'Neil, Andrew S. Zeft, Ilona S. Szer, Sarah Ringold, Hermine I. Brunner, Laura E. Schanberg, Robert P. Sundel, Diana Milojevic, Marilynn G. Punaro, Peter Chira, Beth S. Gottlieb, Gloria C. Higgins, Norman Todd Ilowite, Yukiko Kimura, Stephanie Hamilton, Anne JohnsonBin Huang, Daniel J. Lovell

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Abstract

Objective To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Methods Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. Results By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (π 2 = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. Conclusion Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.

Original languageEnglish (US)
Pages (from-to)2012-2021
Number of pages10
JournalArthritis and Rheumatism
Volume64
Issue number6
DOIs
StatePublished - Jun 2012

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Juvenile Arthritis
Secondary Prevention
Rheumatoid Factor
Placebos
Prednisolone
Methotrexate
Therapeutics
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Wallace, C. A., Giannini, E. H., Spalding, S. J., Hashkes, P. J., O'Neil, K. M., Zeft, A. S., ... Lovell, D. J. (2012). Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis and Rheumatism, 64(6), 2012-2021. https://doi.org/10.1002/art.34343

Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. / Wallace, Carol A.; Giannini, Edward H.; Spalding, Steven J.; Hashkes, Philip J.; O'Neil, Kathleen M.; Zeft, Andrew S.; Szer, Ilona S.; Ringold, Sarah; Brunner, Hermine I.; Schanberg, Laura E.; Sundel, Robert P.; Milojevic, Diana; Punaro, Marilynn G.; Chira, Peter; Gottlieb, Beth S.; Higgins, Gloria C.; Ilowite, Norman Todd; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J.

In: Arthritis and Rheumatism, Vol. 64, No. 6, 06.2012, p. 2012-2021.

Research output: Contribution to journalArticle

Wallace, CA, Giannini, EH, Spalding, SJ, Hashkes, PJ, O'Neil, KM, Zeft, AS, Szer, IS, Ringold, S, Brunner, HI, Schanberg, LE, Sundel, RP, Milojevic, D, Punaro, MG, Chira, P, Gottlieb, BS, Higgins, GC, Ilowite, NT, Kimura, Y, Hamilton, S, Johnson, A, Huang, B & Lovell, DJ 2012, 'Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis', Arthritis and Rheumatism, vol. 64, no. 6, pp. 2012-2021. https://doi.org/10.1002/art.34343
Wallace CA, Giannini EH, Spalding SJ, Hashkes PJ, O'Neil KM, Zeft AS et al. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis and Rheumatism. 2012 Jun;64(6):2012-2021. https://doi.org/10.1002/art.34343
Wallace, Carol A. ; Giannini, Edward H. ; Spalding, Steven J. ; Hashkes, Philip J. ; O'Neil, Kathleen M. ; Zeft, Andrew S. ; Szer, Ilona S. ; Ringold, Sarah ; Brunner, Hermine I. ; Schanberg, Laura E. ; Sundel, Robert P. ; Milojevic, Diana ; Punaro, Marilynn G. ; Chira, Peter ; Gottlieb, Beth S. ; Higgins, Gloria C. ; Ilowite, Norman Todd ; Kimura, Yukiko ; Hamilton, Stephanie ; Johnson, Anne ; Huang, Bin ; Lovell, Daniel J. / Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. In: Arthritis and Rheumatism. 2012 ; Vol. 64, No. 6. pp. 2012-2021.
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abstract = "Objective To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Methods Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. Results By 6 months, clinical inactive disease had been achieved in 17 (40{\%}) of 42 patients in arm 1 and 10 (23{\%}) of 43 patients in arm 2 (π 2 = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. Conclusion Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.",
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T1 - Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis

AU - Wallace, Carol A.

AU - Giannini, Edward H.

AU - Spalding, Steven J.

AU - Hashkes, Philip J.

AU - O'Neil, Kathleen M.

AU - Zeft, Andrew S.

AU - Szer, Ilona S.

AU - Ringold, Sarah

AU - Brunner, Hermine I.

AU - Schanberg, Laura E.

AU - Sundel, Robert P.

AU - Milojevic, Diana

AU - Punaro, Marilynn G.

AU - Chira, Peter

AU - Gottlieb, Beth S.

AU - Higgins, Gloria C.

AU - Ilowite, Norman Todd

AU - Kimura, Yukiko

AU - Hamilton, Stephanie

AU - Johnson, Anne

AU - Huang, Bin

AU - Lovell, Daniel J.

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N2 - Objective To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Methods Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. Results By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (π 2 = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. Conclusion Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.

AB - Objective To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Methods Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. Results By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (π 2 = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. Conclusion Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.

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