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Clinical Rheumatology

, Volume 38, Issue 4, pp 1025–1030 | Cite as

The frequency of infections in patients with juvenile idiopathic arthritis on biologic agents: 1-year prospective study

  • Deniz Aygun
  • Sezgin Sahin
  • Amra Adrovic
  • Kenan Barut
  • Haluk Cokugras
  • Yıldız Camcıoglu
  • Ozgur KasapcopurEmail author
Original Article

Abstract

Introduction

The most effective and concurrently the safest treatment regimen selection is important to provide early control of juvenile idiopathic arthritis (JIA) and to have an acceptable quality of life. The effectivity of biologic agents as well as standard disease-modifying drugs is well documented in treatment of JIA. In spite of their high benefit, these drugs have the risk of serious infections. Herein, we conducted a prospective study to investigate the infectious complications of biologic agents in patients diagnosed with JIA.

Methods

Patients on biologic treatment regimen were examined by the pediatric infectious disease specialist in every 2 months during 1-year long.

Results

Throughout the study period, 57% (n:175) of the patients developed infection and 43% (n:132) of them completed this period without any infection. Upper respiratory tract infections which were treated in outpatient clinic were the most common infection. Only three serious infections (two pneumonia, one pleural effusion), which required hospitalization, developed. The infection rate was highest in systemic JIA and lowest in enthesitis-related arthritis (p < 0.001). The total rate of infection development after 1-year period was lowest for etanercept; it was highest for the patients on infliximab treatment (p < 0.001).

Conclusion

We comment that the altered immune system of JIA can be responsible from the serious infections irrespective of immunosuppressive therapy. Biologic agents can be safely used in JIA evaluating the loss and benefit statement.

Keywords

Biologic agents Etanercept Infection Juvenile idiopathic arthritis 

Notes

Compliance with ethical standards

The study protocol was in line with the guidelines of the 1975 Declaration of Helsinki. Ethics Committee approval was obtained from Faculty Local Ethics Committee (367966). Written informed consents were taken from all parents before commencing this study.

Disclosures

None.

References

  1. 1.
    Barut K, Adrovic A, Şahin S, Kasapçopur Ö (2017) Juvenile idiopathic arthritis. Balkan Med J 34:90–101CrossRefGoogle Scholar
  2. 2.
    Gowdie PJ, Tse SM (2012) Juvenile idiopathic arthritis. Pediatr Clin N Am 59:301–327CrossRefGoogle Scholar
  3. 3.
    Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM et al (2011) American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res 63:465–482CrossRefGoogle Scholar
  4. 4.
    Weiss JE, Ilowite NT (2005) Juvenile idiopathic arthritis. Pediatr Clin N Am 52:413–442CrossRefGoogle Scholar
  5. 5.
    Ravelli A, Martini A (2007) Juvenile idiopathic arthritis. Lancet 369:767–778CrossRefGoogle Scholar
  6. 6.
    Klein A, Horneff G (2009) Treatment strategies for juvenile idiopathic arthritis. Expert Opin Pharmacother 10:3049–3060CrossRefGoogle Scholar
  7. 7.
    Kilic O, Kasapcopur O, Camcioglu Y, Cokugras H, Arisoy N, Akcakaya N (2012) Is it safe to use anti-TNF-α agents for tuberculosis in children suffering with chronic rheumatic disease? Rheumatol Int 32:2675–2679CrossRefGoogle Scholar
  8. 8.
    Lovell DJ, Reiff A, Jones OY, Schneider R, Nocton J, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore JB, White B, Giannini EH, Pediatric Rheumatology Collaborative Study Group (2006) Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 54:1987–1994CrossRefGoogle Scholar
  9. 9.
    Lovell DJ, Reiff A, Ilowite NT, Wallace CA, Chon Y, Lin SL, Baumgartner SW, Giannini EH, Pediatric Rheumatology Collaborative Study Group (2008) Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum 58:1496–1504CrossRefGoogle Scholar
  10. 10.
    Becker I, Horneff G (2017) Risk of serious infection in juvenile idiopathic arthritis patients associated with tumor necrosis factor inhibitors and disease activity in the German biologics in pediatric rheumatology registry. Arthritis Care Res 69:552–560CrossRefGoogle Scholar
  11. 11.
    Prince FHM, Twilt M, ten Cate R, van Rossum MA, Armbrust W, Hoppenreijs EP et al (2009) Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register. Ann Rheum Dis 68:635–641CrossRefGoogle Scholar
  12. 12.
    Beukelman T, Xie F, Baddley JW, Chen L, Delzell E, Grijalva CG, Mannion ML, Patkar NM, Saag KG, Winthrop KL, Curtis JR, on behalf of the SABER Collaboration (2013) Brief report: incidence of selected opportunistic infections among children with juvenile idiopathic arthritis. Arthritis Rheum 65:1384–1389CrossRefGoogle Scholar
  13. 13.
    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 31:390–392Google Scholar
  14. 14.
    Prakken B, Albani S, Martini A (2011) Juvenile idiopathic arthritis. Lancet 377:2138–2149CrossRefGoogle Scholar
  15. 15.
    De Benedetti F, Massa M, Pignatti P, Albani S, Novick D, Martini A (1994) Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 93:2114–2119CrossRefGoogle Scholar
  16. 16.
    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 responseto IL-1blockade. J Exp Med 201:1479–1486CrossRefGoogle Scholar
  17. 17.
    Woo P (2002) Cytokines and juvenilei diopathic arthritis. Curr Rheumatol Rep 4:452–457CrossRefGoogle Scholar
  18. 18.
    Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, Nemcova D, Mouy R, Sandborg C, Bohnsack J, Elewaut D, Foeldvari I, Gerloni V, Rovensky J, Minden K, Vehe RK, Weiner LW, Horneff G, Huppertz HI, Olson NY, Medich JR, Carcereri-de-Prati R, McIlraith M, Giannini EH, Martini A, Pediatric Rheumatology Collaborative Study Group, Pediatric Rheumatology International Trials Organisation (2008) Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med 359:810–820CrossRefGoogle Scholar
  19. 19.
    Lahdenne P, Vahasalo P, Honkanen V (2003) Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann Rheum Dis 62:245–247CrossRefGoogle Scholar
  20. 20.
    Horneff G, Burgos-Vargas R, Constantin T, Foeldvari I, Vojinovic J, Chasnyk VG et al (2014) Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study. Ann Rheum Dis 73:1114–1122CrossRefGoogle Scholar
  21. 21.
    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, for the Childhood Arthritis and Rheumatology Research Alliance (2012) Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis Rheum 64:2012–2021CrossRefGoogle Scholar
  22. 22.
    Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, Higgins G, Gottlieb B, Singer NG, Pediatric Rheumatology Collaborative Study Group, Chon Y, Lin SL, Baumgartner SW (2009) Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum 60:2794–2804CrossRefGoogle Scholar
  23. 23.
    Horneff G, Klein A, Klotsche J, Minden K, Huppertz HI, Weller-Heinemann F, Kuemmerle-Deschner J, Haas JP, Hospach A (2016) Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab. Arthritis Res Ther 18:272CrossRefGoogle Scholar
  24. 24.
    Davies R, Southwood TR, Kearsley-Fleet L, Lunt M, Hyrich KL, British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (2015) Medically significant infections are increased in patients with juvenile idiopathic arthritis treated with etanercept: results from the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study. Arthritis Rheum 67:2487–2494CrossRefGoogle Scholar
  25. 25.
    Horneff G (2015) Biologic-associated infections in pediatric rheumatology. Curr Rheumatol Rep 17:66CrossRefGoogle Scholar
  26. 26.
    Walters HM, Pan N, Lehman TJ, Adams A, Huang WT, Sitaras L et al (2015) A prospective study comparing infection risk and disease activity in children with juvenile idiopathic arthritis treated with and without tumor necrosis factor-alpha inhibitors. Clin Rheumatol 34:457–464CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  1. 1.Department of Pediatric Infectious Disease, Cerrahpasa Medical SchoolIstanbul UniversityIstanbulTurkey
  2. 2.Department of Pediatric Rheumatology, Cerrahpasa Medical SchoolIstanbul UniversityIstanbulTurkey

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