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Biologic Response Modifiers in Pediatric Rheumatology

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Pediatric Rheumatology

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Abstract

To introduce the concept of biologic response modifiers (BRMs)

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References

  1. Hashkes PJ, Uziel Y, Laxer RM. The safety profile of biologic therapies for juvenile idiopathic arthritis. Nat Rev Rheumatol. 2010;6:561–71.

    Article  CAS  PubMed  Google Scholar 

  2. Ruperto N, Martini A. Pediatric rheumatology: JIA, treatment and possible risk of malignancies. Nat Rev Rheumatol. 2011;7:6–7.

    Article  PubMed  Google Scholar 

  3. Ruperto N, Martini A. Juvenile idiopathic arthritis and malignancy. Rheumatology (Oxford). 2014;53:968–74.

    Article  Google Scholar 

  4. Beukelman T, Xie F, Chen L, Baddley JW, Delzell E, Grijalva CG, et al. Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum. 2012;64:2773–80.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Diak P, Siegel J, La GL, Choi L, Lemery S, McMahon A. Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the Food and Drug Administration. Arthritis Rheum. 2010;62:2517–24.

    Article  PubMed  Google Scholar 

  6. Horneff G, Schmeling H, Biedermann T, Foeldvari I, Ganser G, Girschick HJ, et al. The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis. 2004;63:1638–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Horneff G, Foeldvari I, Minden K, Moebius D, Hospach T. Report on malignancies in the German juvenile idiopathic arthritis registry. Rheumatology (Oxford). 2011;50:230–6.

    Article  CAS  Google Scholar 

  8. Simard JF, Neovius M, Hagelberg S, Askling J. Juvenile idiopathic arthritis and risk of cancer: a nationwide cohort study. Arthritis Rheum. 2010;62:3776–82.

    Article  CAS  PubMed  Google Scholar 

  9. Beukelman T, Haynes K, Curtis JR, Xie F, Chen L, Bemrich-Stolz CJ, et al. Rates of malignancy associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum. 2012;64:1263–71.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Nordstrom BL, Mines D, Gu Y, Mercaldi C, Aquino P, Harrison MJ. Risk of malignancy in children with juvenile idiopathic arthritis not treated with biologic agents. Arthritis Care Res (Hoboken). 2012;64:1357–64.

    Article  Google Scholar 

  11. Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA et al. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Arthritis Rheum. 2010;62(6):1792–802.

    Google Scholar 

  12. Ruperto N, Quartier P, Wulffraat N, Woo P, Loy A, Mouy R et al. Evaluation of safety and preliminary efficacy of canakinumab (ACZ885), a new IL-1 beta blocking monoclonal antibody has a beneficial effect in children with systemic juvenile idiopathic arthritis (sJIA). Arth Rheumat. 2009;60:s769. 2011. Ref Type: Abstract.

    Google Scholar 

  13. Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70:747–54.

    Article  CAS  PubMed  Google Scholar 

  14. Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008;371:998–1006.

    Article  CAS  PubMed  Google Scholar 

  15. Ilowite N, Porras O, Reiff A, Rudge S, Punaro M, Martin A, et al. Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study. Clin Rheumatol. 2009;28:129–37.

    Article  PubMed  Google Scholar 

  16. Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med. 2000;342:763–9.

    Article  CAS  PubMed  Google Scholar 

  17. Horneff G, Ebert A, Fitter S, Minden K, Foeldvari I, Kummerle-Deschner J, et al. Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis. Rheumatology (Oxford). 2009;48:916–9.

    Article  CAS  Google Scholar 

  18. Gerloni V, Pontikaki I, Gattinara M, Fantini F. Focus on adverse events of tumour necrosis factor alpha blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients. Ann Rheum Dis. 2008;67:1145–52.

    Article  CAS  PubMed  Google Scholar 

  19. Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M, et al. Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum. 2003;48:1093–101.

    Article  CAS  PubMed  Google Scholar 

  20. Papsdorf V, Horneff G. Complete control of disease activity and remission induced by treatment with etanercept in juvenile idiopathic arthritis. Rheumatology (Oxford). 2011;50:214–21.

    Article  CAS  Google Scholar 

  21. Otten MH, Prince FH, Armbrust W, Ten CR, Hoppenreijs EP, Twilt M, et al. Factors associated with treatment response to etanercept in juvenile idiopathic arthritis. JAMA. 2011;306:2340–7.

    Article  CAS  PubMed  Google Scholar 

  22. Halbig M, Horneff G. Improvement of functional ability in children with juvenile idiopathic arthritis by treatment with etanercept. Rheumatol Int. 2009;30:229–38.

    Article  CAS  PubMed  Google Scholar 

  23. Prince FH, Geerdink LM, Borsboom GJ, Twilt M, van Rossum MA, Hoppenreijs EP, et al. Major improvements in health-related quality of life during the use of etanercept in patients with previously refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2010;69:138–42.

    Article  CAS  PubMed  Google Scholar 

  24. Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, et al. Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:3259–64.

    Article  CAS  PubMed  Google Scholar 

  25. Billiau AD, Loop M, Le PQ, Berthet F, Philippet P, Kasran A, et al. Etanercept improves linear growth and bone mass acquisition in MTX-resistant polyarticular-course juvenile idiopathic arthritis. Rheumatology (Oxford). 2010;49:1550–8.

    Article  CAS  Google Scholar 

  26. Nielsen S, Ruperto N, Gerloni V, Simonini G, Cortis E, Lepore L, et al. Preliminary evidence that etanercept may reduce radiographic progression in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2008;26:688–92.

    CAS  PubMed  Google Scholar 

  27. Kimura Y, Pinho P, Walco G, Higgins G, Hummell D, Szer I, et al. Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol. 2005;32:935–42.

    CAS  PubMed  Google Scholar 

  28. Prince FH, Twilt M, Ten CR, van Rossum MA, Armbrust W, Hoppenreijs EP, et al. Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register. Ann Rheum Dis. 2009;68:635–41.

    Article  CAS  PubMed  Google Scholar 

  29. Southwood TR, Foster HE, Davidson JE, Hyrich KL, Cotter CB, Wedderburn LR, et al. Duration of etanercept treatment and reasons for discontinuation in a cohort of juvenile idiopathic arthritis patients. Rheumatology (Oxford). 2011;50:189–95.

    Article  CAS  Google Scholar 

  30. Tynjala P, Vahasalo P, Honkanen V, Lahdenne P. Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis. Ann Rheum Dis. 2009;68:552–7.

    Article  CAS  PubMed  Google Scholar 

  31. Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005;201:1479–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. De Benedetti F, Martini A. Is systemic juvenile rheumatoid arthritis an interleukin 6 mediated disease? J Rheumatol. 1998;25:203–7.

    PubMed  Google Scholar 

  33. Solari N, Palmisani E, Consolaro A, Pistorio A, Viola S, Buoncompagni A, et al. Factors associated with achievement of inactive disease in children with juvenile idiopathic arthritis treated with etanercept. J Rheumatol. 2013;40:192–200.

    Article  CAS  PubMed  Google Scholar 

  34. Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, et al. Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2794–804.

    Article  CAS  PubMed  Google Scholar 

  35. Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, et al. Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:3259–64.

    Article  CAS  PubMed  Google Scholar 

  36. Horneff G, De BF, Foeldvari I, Girschick HJ, Michels H, Moebius D, et al. Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis. 2009;68:519–25.

    Article  CAS  PubMed  Google Scholar 

  37. Prince FH, Twilt M, Simon SC, van Rossum MA, Armbrust W, Hoppenreijs EP, et al. When and how to stop etanercept after successful treatment of patients with juvenile idiopathic arthritis. Ann Rheum Dis. 2009;68:1228–9.

    Article  CAS  PubMed  Google Scholar 

  38. Hashkes PJ, Shajrawi I. Sarcoid-related uveitis occurring during etanercept therapy. Clin Exp Rheumatol. 2003;21:645–6.

    CAS  PubMed  Google Scholar 

  39. Kuek A, Hazleman BL, Gaston JH, Ostor AJ. Successful treatment of refractory polyarticular juvenile idiopathic arthritis with rituximab. Rheumatology (Oxford). 2006;45:1448–9.

    Article  CAS  Google Scholar 

  40. Saurenmann RK, Levin AV, Feldman BM, Laxer RM, Schneider R, Silverman ED. Risk of new-onset uveitis in patients with juvenile idiopathic arthritis treated with anti-TNFalpha agents. J Pediatr. 2006;149:833–6.

    Article  CAS  PubMed  Google Scholar 

  41. Kaneko U, Kishi T, Kikuchi M, Hara R, Shinoki T, Miyamae T, et al. Two patients with childhood-onset Behcet’s disease successfully treated by anti-tumor necrosis factor therapy. Nihon Rinsho Meneki Gakkai Kaishi. 2010;33:157–61.

    Article  PubMed  Google Scholar 

  42. Sakallioglu O, Duzova A, Ozen S. Etanercept in the treatment of arthritis in a patient with familial Mediterranean fever. Clin Exp Rheumatol. 2006;24:435–7.

    CAS  PubMed  Google Scholar 

  43. Kusuhara K, Hoshina T, Saito M, Ishimura M, Inoue H, Horiuchi T, et al. Successful treatment of a patient with tumor necrosis factor receptor-associated periodic syndrome using a half-dose of etanercept. Pediatr Int. 2012;54:552–5.

    Article  PubMed  Google Scholar 

  44. Choueiter NF, Olson AK, Shen DD, Portman MA. Prospective open-label trial of etanercept as adjunctive therapy for kawasaki disease. J Pediatr. 2010;157:960–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ruperto N, Lovell DJ, Cuttica R, Wilkinson N, Woo P, Espada G, et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007;56:3096–106.

    Article  CAS  PubMed  Google Scholar 

  46. Ruperto N, Lovell DJ, Cuttica R, Woo P, Meiorin S, Wouters C, et al. Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis: findings from an open-label treatment extension. Ann Rheum Dis. 2010;69:718–22.

    Article  CAS  PubMed  Google Scholar 

  47. Smith EM, Foster HE, Beresford MW. The development and assessment of biological treatments for children. Br J Clin Pharmacol. 2015;79:379–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359:810–20.

    Article  CAS  PubMed  Google Scholar 

  49. Durmoqicz EL. Pediatric focused safety review: adalimumab. FDA [online]. 2010. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM193197.pdf.

  50. Biester S, Deuter C, Michels H, Haefner R, Kuemmerle-Deschner J, Doycheva D, et al. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol. 2007;91:319–24.

    Article  PubMed  Google Scholar 

  51. Tynjala P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, et al. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology (Oxford). 2008;47:339–44.

    Article  CAS  Google Scholar 

  52. Gattorno M, Piccini A, Lasiglie D, Tassi S, Brisca G, Carta S, et al. The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2008;58:1505–15.

    Article  CAS  PubMed  Google Scholar 

  53. Nigrovic PA, Mannion M, Prince FH, Zeft A, Rabinovich CE, Van Rossum MA, et al. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum. 2011;63:545–55.

    Article  CAS  PubMed  Google Scholar 

  54. Vastert SJ, de Jager W, Noordman BJ, Holzinger D, Kuis W, Prakken BJ, et al. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis: results of a prospective cohort study. Arthritis Rheumatol. 2014;66:1034–43.

    Article  CAS  PubMed  Google Scholar 

  55. Swart JF, Barug D, Mohlmann M, Wulffraat NM. The efficacy and safety of interleukin-1-receptor antagonist anakinra in the treatment of systemic juvenile idiopathic arthritis. Expert Opin Biol Ther. 2010;10:1743–52.

    Article  CAS  PubMed  Google Scholar 

  56. Nigrovic PA. Review: is there a window of opportunity for treatment of systemic juvenile idiopathic arthritis? Arthritis Rheumatol. 2014;66:1405–13.

    Article  CAS  PubMed  Google Scholar 

  57. Zeft A, Hollister R, LaFleur B, Sampath P, Soep J, McNally B, et al. Anakinra for systemic juvenile arthritis: the Rocky Mountain experience. J Clin Rheumatol. 2009;15:161–4.

    Article  PubMed  Google Scholar 

  58. Caorsi R, Federici S, Gattorno M. Biologic drugs in autoinflammatory syndromes. Autoimmun Rev. 2012;12:81–6.

    Article  CAS  PubMed  Google Scholar 

  59. Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2396–406.

    Article  CAS  PubMed  Google Scholar 

  60. De Benedetti F, Massa M, Pignatti P, Albani S, Novick D, Martini A. Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL- 6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest. 1994;93:2114–9.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369:767–78.

    Article  CAS  PubMed  Google Scholar 

  62. De Benedetti F, Pignatti P, Gerloni V, Massa M, Sartirana P, Caporali R, et al. Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis. J Rheumatol. 1997;24:1403–9.

    PubMed  Google Scholar 

  63. de Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2385–95.

    Article  PubMed  Google Scholar 

  64. Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015;74:1110–7.

    Article  PubMed  Google Scholar 

  65. Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372:383–91.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Istituto Giannina Gaslini, University of Genova and Second Division of Pediatrics, Genova, Italy

    Alessandro Consolaro MD, PhD

  2. Istituto Giannina Gaslini, Pediatric Rheumatology International Trials Organization and Second Division of Pediatrics, Genova, Italy

    Nicola Ruperto MD, MPH

Authors
  1. Alessandro Consolaro MD, PhD
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  2. Nicola Ruperto MD, MPH
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Corresponding author

Correspondence to Alessandro Consolaro MD, PhD .

Editor information

Editors and Affiliations

  1. Pediatric Rheumatology Division Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India

    Sujata Sawhney

  2. Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

    Amita Aggarwal

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Consolaro, A., Ruperto, N. (2017). Biologic Response Modifiers in Pediatric Rheumatology. In: Sawhney, S., Aggarwal, A. (eds) Pediatric Rheumatology. Springer, Singapore. https://doi.org/10.1007/978-981-10-1750-6_8

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  • DOI: https://doi.org/10.1007/978-981-10-1750-6_8

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