Skip to main content

Advertisement

SpringerLink
Log in

Impact of biologics on disease course in systemic onset juvenile idiopathic arthritis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

To analyze our cohort of patients with systemic onset juvenile idiopathic arthritis (SoJIA) and investigate the impact of biologic disease-modifying antirheumatic drugs (BDMARDs) on disease course. Children who were diagnosed with SoJIA according to International League of Associations for Rheumatology (ILAR) criteria in Boston Children’s Hospital between January 1996 and December 2015 were included. Data were collected from patients’ charts retrospectively. Demographic features, disease course, and medication usage were identified. There were 76 patients who met ILAR criteria. Most common presenting features were fever (100%), arthralgia (92%), rash (87%), and arthritis (83%). Median follow-up was 69 months. At last visit, 18% still had active disease. Disease course was monophasic in 18 patients (24%), persistent in 24 patients (32%), and polycyclic in 34 patients (45%). Thirty-three percent (n, 6) of children with monophasic disease was diagnosed before 2004 and 67% (n, 12) was diagnosed after 2004 (p = 0.08). Sixty-six percent was treated with a BDMARD. Anakinra (37%) was the most common prescribed BDMARD. Monophasic disease was less common in patients treated with a BDMARD (n, 6, 12%) compared to children not treated with a BDMARD (n, 12, 46%) (p = 0.01). BDMARDs are started earlier (rs, − 0.67; p < 0.001) and diagnosis of SoJIA is made sooner after symptom onset in recent years (rs, − 0.37; p = 0.001). Most patients in our cohort were able to achieve remission. Proportion of monophasic disease tends to increase after 2004 although not statistically significant. In recent years, physicians tend to diagnose SoJIA earlier and treat more aggressively early in the course of the disease with BMARDs. Future prospective research in larger cohorts investigating the effects of BDMARDs on disease course and predictive factors for outcome is needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Fantini F, Gerloni V, Gattinara M, Cimaz R, Arnoldi C, Lupi E (2003) Remission in juvenile chronic arthritis: a cohort study of 683 consecutive cases with a mean 10 year followup. J Rheumatol 30:579–584

    PubMed  Google Scholar 

  2. Sengler C, Klotsche J, Niewerth M, Liedmann I, Föll D, Heiligenhaus A, Ganser G, Horneff G, Haas JP, Minden K (2015) The majority of newly diagnosed patients with juvenile idiopathic arthritis reach an inactive disease state within the first year of specialised care: data from a German inception cohort. RMD Open 1:e000074

    Article  Google Scholar 

  3. Danner S, Sordet C, Terzic J, Donato L, Velten M, Fischbach M, Sibilia J (2006) Epidemiology of juvenile idiopathic arthritis in Alsace, France. J Rheumatol 33:1377–1381

    PubMed  Google Scholar 

  4. Seth V, Kabra SK, Semwal OP, Jain Y (1996) Clinico-immunological profile in juvenile rheumatoid arthritis—an Indian experience. Indian J Pediatr 63:293–300

    Article  CAS  Google Scholar 

  5. Fitzpatrick L, Broadaway KA, Ponder L, Angeles-Han ST, Jenkins K, Rouster-Stevens K, Pelajo CF, Conneely K, Epstein MP, Lopez-Benitez J, Vogler LB, Prahalad S, CARRA Registry Investigators (2016) Phenotypic characterization of juvenile idiopathic arthritis in African American children. J Rheumatol 43:799–803

    Article  Google Scholar 

  6. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P, International League of Associations for Rheumatology (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392

    PubMed  Google Scholar 

  7. Cassidy JT, Petty RE (2016) Textbook of pediatric rheumatology. Elsevier, Philadelphia

    Google Scholar 

  8. Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J (2005) 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 201:1479–1486

    Article  CAS  Google Scholar 

  9. Pignatti P, Vivarelli M, Meazza C, Rizzolo MG, Martini A, De Benedetti F (2001) Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J Rheumatol 28:1670–1676

    CAS  PubMed  Google Scholar 

  10. Nigrovic PA, Mannion M, Prince FH, Zeft A, Rabinovich CE, van Rossum MA, Cortis E, Pardeo M, Miettunen PM, Janow G, Birmingham J, Eggebeen A, Janssen E, Shulman AI, Son MB, Hong S, Jones K, Ilowite NT, Cron RQ, Higgins GC (2011) Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum 63:545–555

    Article  CAS  Google Scholar 

  11. Vastert SJ, de Jager W, Noordman BJ, Holzinger D, Kuis W, Prakken BJ, Wulffraat NM (2014) 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 Rheum 66:1034–1043

    Article  CAS  Google Scholar 

  12. Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, Brik R, McCann L, Kasapcopur O, Rutkowska-Sak L, Schneider R, Berkun Y, Calvo I, Erguven M, Goffin L, Hofer M, Kallinich T, Oliveira SK, Uziel Y, Viola S, Nistala K, Wouters C, Cimaz R, Ferrandiz MA, Flato B, Gamir ML, Kone-Paut I, Grom A, Magnusson B, Ozen S, Sztajnbok F, Lheritier K, Abrams K, Kim D, Martini A, Lovell DJ, Printo PRCSG (2012) Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med 367:2396–2406

    Article  CAS  Google Scholar 

  13. Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, Iwata N, Umebayashi H, Murata T, Miyoshi M, Tomiita M, Nishimoto N, Kishimoto T (2008) Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 371:998–1006

    Article  CAS  Google Scholar 

  14. Janow G, Schanberg LE, Setoguchi S, Hasselblad V, Mellins ED, Schneider R, Kimura Y, CARRA Legacy Registry Investigators (2016) The systemic juvenile idiopathic arthritis cohort of the Childhood Arthritis and Rheumatology Research Alliance Registry: 2010-2013. J Rheumatol 43:1755–1762

    Article  Google Scholar 

  15. Lomater C, Gerloni V, Gattinara M, Mazzotti J, Cimaz R, Fantini F (2000) Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J Rheumatol 27:491–496

    CAS  PubMed  Google Scholar 

  16. Minden K, Kiessling U, Listing J, Niewerth M, Döring E, Meincke J, Schöntube M, Zink A (2000) Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy. J Rheumatol 27:2256–2263

    CAS  PubMed  Google Scholar 

  17. Singh-Grewal D, Schneider R, Bayer N, Feldman BM (2006) Predictors of disease course and remission in systemic juvenile idiopathic arthritis: significance of early clinical and laboratory features. Arthritis Rheum 54:1595–1601

    Article  CAS  Google Scholar 

  18. Bailey KM, McDonagh JE, Prieur AM (2004) Systemic juvenile idiopathic arthritis presenting in a young child with long term disability as an adolescent. Ann Rheum Dis 63:1544–1548

    Article  CAS  Google Scholar 

  19. Oen K, Malleson PN, Cabral DA, Rosenberg AM, Petty RE, Cheang M (2002) Disease course and outcome of juvenile rheumatoid arthritis in a multicenter cohort. J Rheumatol 29:1989–1999

    PubMed  Google Scholar 

  20. Packham JC, Hall MA (2002) Long-term follow-up of 246 adults with juvenile idiopathic arthritis: functional outcome. Rheumatology (Oxford) 41:1428–1435

    Article  CAS  Google Scholar 

  21. Nigrovic PA, White PH (2006) Care of the adult with juvenile rheumatoid arthritis. Arthritis Rheum 55:208–216

    Article  Google Scholar 

  22. Spiegel LR, Schneider R, Lang BA, Birdi N, Silverman ED, Laxer RM, Stephens D, Feldman BM (2000) Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: a multicenter cohort study. Arthritis Rheum 43:2402–2409

    Article  CAS  Google Scholar 

  23. Russo RA, Katsicas MM (2013) Patients with very early-onset systemic juvenile idiopathic arthritis exhibit more inflammatory features and a worse outcome. J Rheumatol 40:329–334

    Article  CAS  Google Scholar 

  24. Modesto C, Woo P, García-Consuegra J, Merino R, García-Granero M, Arnal C, Prieur AM (2001) Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis. Clin Exp Rheumatol 19:211–217

    CAS  PubMed  Google Scholar 

  25. Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, Aricò M, Avcin T, Behrens EM, De Benedetti F, Filipovic L, Grom AA, Henter JI, Ilowite NT, Jordan MB, Khubchandani R, Kitoh T, Lehmberg K, Lovell DJ, Miettunen P, Nichols KE, Ozen S, Pachlopnik Schmid J, Ramanan AV, Russo R, Schneider R, Sterba G, Uziel Y, Wallace C, Wouters C, Wulffraat N, Demirkaya E, Brunner HI, Martini A, Ruperto N, Cron RQ, Paediatric Rheumatology International Trials Organisation, Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology Collaborative Study Group, Histiocyte Society (2016) 2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis 75:481–489

    Article  CAS  Google Scholar 

  26. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, Mei Z, Curtin LR, Roche AF, Johnson CL (2000) CDC growth charts: United States. Adv Data 314:1–27

    Google Scholar 

  27. Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N, Childhood Arthritis Rheumatology Research Alliance, Pediatric Rheumatology Collaborative Study Group, Paediatric Rheumatology International Trials Organisation (2011) American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res 63:929–936

    Article  Google Scholar 

  28. Wallace CA, Huang B, Bandeira M, Ravelli A, Giannini EH (2005) Patterns of clinical remission in select categories of juvenile idiopathic arthritis. Arthritis Rheum 52:3554–3562

    Article  Google Scholar 

  29. Guzman J, Oen K, Tucker LB, Huber AM, Shiff N, Boire G, Scuccimarri R, Berard R, Tse SM, Morishita K, Stringer E, Johnson N, Levy DM, Duffy KW, Cabral DA, Rosenberg AM, Larché M, Dancey P, Petty RE, Laxer RM, Silverman E, Miettunen P, Chetaille AL, Haddad E, Houghton K, Spiegel L, Turvey SE, Schmeling H, Lang B, Ellsworth J, Ramsey S, Bruns A, Campillo S, Benseler S, Chédeville G, Schneider R, Yeung R, Duffy CM, ReACCh-Out investigators (2015) The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis 74:1854–1860

    Article  CAS  Google Scholar 

  30. Klotsche J, Raab A, Niewerth M, Sengler C, Ganser G, Kallinich T, Niehues T, Hufnagel M, Thon A, Hospach T, Horneff G, Minden K (2016) Outcome and trends in treatment of systemic juvenile idiopathic arthritis in the German National Pediatric Rheumatological Database from 2000 to 2013. Arthritis Rheum 68:3023–3034

    Article  CAS  Google Scholar 

  31. Woerner A, Uettwiller F, Melki I, Mouy R, Wouters C, Bader-Meunier B, Quartier P (2015) Biological treatment in systemic juvenile idiopathic arthritis: achievement of inactive disease or clinical remission on a first, second or third biological agent. RMD Open 1:e000036

    Article  CAS  Google Scholar 

  32. Behrens EM, Beukelman T, Gallo L, Spangler J, Rosenkranz M, Arkachaisri T, Ayala R, Groh B, Finkel TH, Cron RQ (2008) Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis: data from the Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR). J Rheumatol 35:343–348

    PubMed  Google Scholar 

  33. Otten MH, Anink J, Prince FH, Twilt M, Vastert SJ, ten Cate R, Hoppenreijs EP, Armbrust W, Gorter SL, van Pelt PA, Kamphuis SS, Dolman KM, Swart JF, van den Berg JM, Koopman-Keemink Y, van Rossum MA, Wulffraat NM, van Suijlekom-Smit LW (2015) Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national Arthritis and Biologics in Children Register. Ann Rheum Dis 74:1379–1386

    Article  Google Scholar 

  34. Hashkes PJ, Wright BM, Lauer MS, Worley SE, Tang AS, Roettcher PA, Bowyer SL (2010) Mortality outcomes in pediatric rheumatology in the US. Arthritis Rheum 62:599–608

    PubMed  Google Scholar 

  35. Woo P (2006) Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Pract Rheumatol 2:28–34

    Article  Google Scholar 

  36. Simon D, Fernando C, Czernichow P, Prieur AM (2002) Linear growth and final height in patients with systemic juvenile idiopathic arthritis treated with longterm glucocorticoids. J Rheumatol 29:1296–1300

    CAS  PubMed  Google Scholar 

  37. De Benedetti F, Brunner H, Ruperto N, Schneider R, Xavier R, Allen R, Brown DE, Chaitow J, Pardeo M, Espada G, Gerloni V, Myones BL, Frane JW, Wang J, Lipman TH, Bharucha KN, Martini A, Lovell D, Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group (2015) Catch-up growth during tocilizumab therapy for systemic juvenile idiopathic arthritis: results from a phase III trial. Arthritis Rheum 67:840–848

    Article  Google Scholar 

  38. Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M, Sibilia J, Koné-Paut I, Gandon-Laloum S, LeBideau M, Bader-Meunier B, Mouy R, Debré M, Landais P, Prieur AM (2003) Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 48:1093–1101

    Article  CAS  Google Scholar 

  39. Russo RA, Katsicas MM, Zelazko M (2002) Etanercept in systemic juvenile idiopathic arthritis. Clin Exp Rheumatol 20:723–726

    CAS  PubMed  Google Scholar 

  40. Kimura Y, Pinho P, Walco G, Higgins G, Hummell D, Szer I, Henrickson M, Watcher S, Reiff A (2005) Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 32:935–942

    CAS  PubMed  Google Scholar 

  41. Ringold S, Weiss PF, Beukelman T, EM DW, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Nigrovic PA, Robinson AB, Vehe RK, American Collge of Rheumatology (2013) 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum 65:2499–2512

    Article  Google Scholar 

  42. Kimura Y, Grevich S, Beukelman T, Morgan E, Nigrovic PA, Mieszkalski K, Graham TB, Ibarra M, Ilowite N, Klein-Gitelman M, Onel K, Prahalad S, Punaro M, Ringold S, Toib D, Van Mater H, Weiss JE, Weiss PF, Schanberg LE, CARRA Registry Investigators (2017) Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans. Pediatr Rheumatol Online J 15:23

    Article  Google Scholar 

  43. De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R, Ravelli A, Schneider R, Woo P, Wouters C, Xavier R, Zemel L, Baildam E, Burgos-Vargas R, Dolezalova P, Garay SM, Merino R, Joos R, Grom A, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A, Printo PRCSG (2012) Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med 367:2385–2395

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Marmara University Pendik Research and Training Hospital, Istanbul, Turkey

    Hatice Ezgi Baris

  2. Rheumatology Program, Division of Immunology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA, 02115-5724, USA

    Hatice Ezgi Baris, Edwin Anderson & Fatma Dedeoglu

  3. Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, Istanbul, Turkey

    Betul Sozeri

Authors
  1. Hatice Ezgi Baris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edwin Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Betul Sozeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatma Dedeoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fatma Dedeoglu.

Ethics declarations

Disclosures

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baris, H.E., Anderson, E., Sozeri, B. et al. Impact of biologics on disease course in systemic onset juvenile idiopathic arthritis. Clin Rheumatol 37, 3263–3273 (2018). https://doi.org/10.1007/s10067-018-4297-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-018-4297-6

Keywords

Search

Navigation