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Published in: Clinical Rheumatology 3/2015

01-03-2015 | Original Article

A prospective study comparing infection risk and disease activity in children with juvenile idiopathic arthritis treated with and without tumor necrosis factor-alpha inhibitors

Authors: Heather M. Walters, Nancy Pan, Thomas J. A. Lehman, Alexa Adams, Wei-Ti Huang, Lemonia Sitaras, Susanna Cunningham-Rundles, Thomas J. Walsh, Sima S. Toussi

Published in: Clinical Rheumatology | Issue 3/2015

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Abstract

Tumor necrosis factor-alpha (TNF-α) inhibitors are effective treatment for juvenile idiopathic arthritis (JIA) but may increase infection rates. However, active JIA may also render patients vulnerable to infection. In this study, we prospectively assessed infection rates in JIA patients treated with and without TNF-α inhibitors and correlated disease activity with infection risk. TNF-α inhibitor-naïve JIA subjects were followed up for 12 months. Subjects initiated on TNF-α inhibitors after enrollment were analyzed in the TNF group. Subjects treated without TNF-α inhibitors were analyzed in the non-TNF group. Questionnaires captured mild or severe infections. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Twenty TNF and 36 non-TNF subjects were analyzed. The total infection rate ratio for TNF versus non-TNF group subjects was 1.14 (95 % CI, 0.78–1.66; p = 0.51). The average rate of infections per month was 0.29 for TNF and 0.24 for non-TNF subjects. No severe infections or hospitalizations occurred in either group. Secondary infectious outcomes were also similar between groups. Controlling for study group, an increase in CHAQ pain score correlated with an increase in several infectious outcome measures. Our results suggest no difference in infection rates between JIA subjects treated with and without TNF-α inhibitors. Additionally, JIA disease activity may have contributed to infection risk in our cohort, irrespective of immunosuppressive therapy. Future analysis of the relationship between treatment regimens, disease activity, and infection rates may help to further delineate predictors of infection risk in JIA patients.
Literature
1.
go back to reference Ruperto N, Lovell DJ, Cuttica R, Wilkinson N, Woo P, Espada G et al (2007) A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 56:3096–3106CrossRefPubMed Ruperto N, Lovell DJ, Cuttica R, Wilkinson N, Woo P, Espada G et al (2007) A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 56:3096–3106CrossRefPubMed
2.
go back to reference Gerloni V, Pontikaki I, Gattinara M, Fantini F (2008) 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 67:1145–1152CrossRefPubMed Gerloni V, Pontikaki I, Gattinara M, Fantini F (2008) 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 67:1145–1152CrossRefPubMed
3.
go back to reference Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ et al (2000) Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med 342:763–769CrossRefPubMed Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ et al (2000) Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med 342:763–769CrossRefPubMed
4.
go back to reference Lovell DJ, Reiff A, Ilowite NT, Wallace CA, Chon Y, Lin S et al (2008) Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum 58:1496–1504CrossRefPubMed Lovell DJ, Reiff A, Ilowite NT, Wallace CA, Chon Y, Lin S et al (2008) Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum 58:1496–1504CrossRefPubMed
5.
go back to reference Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K (2008) Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med 359:810–820CrossRefPubMed Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K (2008) Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med 359:810–820CrossRefPubMed
6.
go back to reference Bracaglia C, Buonuomo PS, Tozzi AE, Pardeo M, Nicolai R, Campana A et al (2012) Safety and efficacy of etanercept in a cohort of patients with juvenile idiopathic arthritis under 4 years of age. J Rheumatol 39:1287–1290CrossRefPubMed Bracaglia C, Buonuomo PS, Tozzi AE, Pardeo M, Nicolai R, Campana A et al (2012) Safety and efficacy of etanercept in a cohort of patients with juvenile idiopathic arthritis under 4 years of age. J Rheumatol 39:1287–1290CrossRefPubMed
7.
go back to reference Mori M, Takei S, Imagawa T, Imanaka H, Nerome Y, Higuchi R et al (2012) Safety and efficacy of long-term etanercept in the treatment of methotrexate-refractory polyarticular-course juvenile idiopathic arthritis in Japan. Mod Rheumatol 22:720–726CrossRefPubMed Mori M, Takei S, Imagawa T, Imanaka H, Nerome Y, Higuchi R et al (2012) Safety and efficacy of long-term etanercept in the treatment of methotrexate-refractory polyarticular-course juvenile idiopathic arthritis in Japan. Mod Rheumatol 22:720–726CrossRefPubMed
8.
go back to reference Hashkes PJ, Uziel Y, Laxer RM (2010) The safety profile of biologic therapies for juvenile idiopathic arthritis. Nat Rev Rheumatol 6:561–571CrossRefPubMed Hashkes PJ, Uziel Y, Laxer RM (2010) The safety profile of biologic therapies for juvenile idiopathic arthritis. Nat Rev Rheumatol 6:561–571CrossRefPubMed
9.
go back to reference Toussi SS, Pan N, Walters HM, Walsh TJ (2013) Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-α inhibitors: systematic review of the literature. Clin Infect Dis 57:1318–1330CrossRefPubMedCentralPubMed Toussi SS, Pan N, Walters HM, Walsh TJ (2013) Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-α inhibitors: systematic review of the literature. Clin Infect Dis 57:1318–1330CrossRefPubMedCentralPubMed
10.
go back to reference Smitten AL, Choi HK, Hochberg MC, Suissa S, Simon T, Testa M et al (2008) The risk of hospitalized infection in patients with rheumatoid arthritis. J Rheumatol 35:387–393PubMed Smitten AL, Choi HK, Hochberg MC, Suissa S, Simon T, Testa M et al (2008) The risk of hospitalized infection in patients with rheumatoid arthritis. J Rheumatol 35:387–393PubMed
11.
go back to reference Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE (2002) Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 46:2287–2293CrossRefPubMed Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE (2002) Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 46:2287–2293CrossRefPubMed
12.
go back to reference Au K, Reed G, Curtis JR, Kremer J, Jeffrey G, Strand V et al (2011) High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis. Ann Rheum Dis 70:785–791CrossRefPubMed Au K, Reed G, Curtis JR, Kremer J, Jeffrey G, Strand V et al (2011) High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis. Ann Rheum Dis 70:785–791CrossRefPubMed
13.
go back to reference Beukelman T, Xie F, Chen L, Baddley JW, Delzell E, Grijalva CG et al (2012) Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 64:2773–2780CrossRefPubMedCentralPubMed Beukelman T, Xie F, Chen L, Baddley JW, Delzell E, Grijalva CG et al (2012) Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 64:2773–2780CrossRefPubMedCentralPubMed
14.
go back to reference Hurd A, Beukelman T (2013) Infectious complications in juvenile idiopathic arthritis. Curr Rheumatol Rep 15:327CrossRefPubMed Hurd A, Beukelman T (2013) Infectious complications in juvenile idiopathic arthritis. Curr Rheumatol Rep 15:327CrossRefPubMed
15.
go back to reference Beukelman T, Xie F, Baddley JW, Chen L, Delzell E, Grijalva CG et al (2013) Brief report: incidence of selected opportunistic infections among children with juvenile idiopathic arthritis. Arthritis Rheum 65:1384–1389CrossRefPubMedCentralPubMed Beukelman T, Xie F, Baddley JW, Chen L, Delzell E, Grijalva CG et al (2013) Brief report: incidence of selected opportunistic infections among children with juvenile idiopathic arthritis. Arthritis Rheum 65:1384–1389CrossRefPubMedCentralPubMed
16.
go back to reference Furst DE (2010) The risk of infections with biologic therapies for rheumatoid arthritis. Semin Arthritis Rheum 39:327–346CrossRefPubMed Furst DE (2010) The risk of infections with biologic therapies for rheumatoid arthritis. Semin Arthritis Rheum 39:327–346CrossRefPubMed
17.
go back to reference Crum NF, Lederman ER, Wallace MR (2005) Infections associated with tumor necrosis factor-alpha antagonists. Medicine (Baltimore) 84:291–302CrossRef Crum NF, Lederman ER, Wallace MR (2005) Infections associated with tumor necrosis factor-alpha antagonists. Medicine (Baltimore) 84:291–302CrossRef
18.
go back to reference Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, Stoyanova-Scholz M et al (2005) Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 52:3403–3412CrossRefPubMed Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, Stoyanova-Scholz M et al (2005) Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 52:3403–3412CrossRefPubMed
19.
go back to reference Askling J, Dixon W (2008) The safety of anti-tumour necrosis factor therapy in rheumatoid arthritis. Curr Opin Rheumatol 20:138–144CrossRefPubMed Askling J, Dixon W (2008) The safety of anti-tumour necrosis factor therapy in rheumatoid arthritis. Curr Opin Rheumatol 20:138–144CrossRefPubMed
20.
go back to reference Patkar NM, Teng GG, Curtis JR, Saag KG (2008) Association of infections and tuberculosis with antitumor necrosis factor alpha therapy. Curr Opin Rheumatol 20:320–326CrossRefPubMed Patkar NM, Teng GG, Curtis JR, Saag KG (2008) Association of infections and tuberculosis with antitumor necrosis factor alpha therapy. Curr Opin Rheumatol 20:320–326CrossRefPubMed
21.
go back to reference Salliot C, Gossec L, Ruyssen-Witrand A, Luc M, Duclos M, Guignard S et al (2007) Infections during tumour necrosis factor-alpha blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients. Rheumatology (Oxford) 46:327–334CrossRef Salliot C, Gossec L, Ruyssen-Witrand A, Luc M, Duclos M, Guignard S et al (2007) Infections during tumour necrosis factor-alpha blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients. Rheumatology (Oxford) 46:327–334CrossRef
22.
go back to reference Kroesen S, Widmer AF, Tyndall A, Hasler P (2003) Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy. Rheumatology (Oxford) 42:617–621CrossRef Kroesen S, Widmer AF, Tyndall A, Hasler P (2003) Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy. Rheumatology (Oxford) 42:617–621CrossRef
23.
go back to reference Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295:2275–2285CrossRefPubMed Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295:2275–2285CrossRefPubMed
24.
go back to reference Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A et al (2009) Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum 60:2794–2804CrossRefPubMed Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A et al (2009) Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum 60:2794–2804CrossRefPubMed
25.
go back to reference Horneff G, De Bock F, Foeldvari I, Girschick HJ, Michels H, Moebius D et al (2009) 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 68:519–525CrossRefPubMed Horneff G, De Bock F, Foeldvari I, Girschick HJ, Michels H, Moebius D et al (2009) 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 68:519–525CrossRefPubMed
26.
go back to reference 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 32:2675–2679CrossRefPubMed 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 32:2675–2679CrossRefPubMed
27.
go back to reference Mohan AK, Coté TR, Block JA, Manadan AM, Siegel JN, Braun MM (2004) Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor. Clin Infect Dis 39:295–299CrossRefPubMed Mohan AK, Coté TR, Block JA, Manadan AM, Siegel JN, Braun MM (2004) Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor. Clin Infect Dis 39:295–299CrossRefPubMed
28.
go back to reference Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO (2004) Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 38:1261–1265CrossRefPubMed Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO (2004) Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 38:1261–1265CrossRefPubMed
29.
go back to reference Elbek O, Uyar M, Aydin N, Borekci S, Bayram N, Bayram H et al (2009) Increased risk of tuberculosis in patients treated with antitumor necrosis factor alpha. Clin Rheumatol 28:421–426CrossRefPubMed Elbek O, Uyar M, Aydin N, Borekci S, Bayram N, Bayram H et al (2009) Increased risk of tuberculosis in patients treated with antitumor necrosis factor alpha. Clin Rheumatol 28:421–426CrossRefPubMed
30.
go back to reference Armbrust W, Kamphuis SSM, Wolfs TWF, Fiselier TJW, Nikkels PG, Kuis W et al (2004) Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis. Rheumatology (Oxford) 43:527–529CrossRef Armbrust W, Kamphuis SSM, Wolfs TWF, Fiselier TJW, Nikkels PG, Kuis W et al (2004) Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis. Rheumatology (Oxford) 43:527–529CrossRef
Metadata
Title
A prospective study comparing infection risk and disease activity in children with juvenile idiopathic arthritis treated with and without tumor necrosis factor-alpha inhibitors
Authors
Heather M. Walters
Nancy Pan
Thomas J. A. Lehman
Alexa Adams
Wei-Ti Huang
Lemonia Sitaras
Susanna Cunningham-Rundles
Thomas J. Walsh
Sima S. Toussi
Publication date
01-03-2015
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 3/2015
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-014-2779-8

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