Population-based cohort study on the risk of malignancy in East Asian children with juvenile idiopathic arthritis

Victor C Kok, Jorng-Tzong Horng, Jing-Long Huang, Kuo-Wei Yeh, Jia-Jing Gau, Cheng-Wei Chang, Lai-Zhen Zhuang, Victor C Kok, Jorng-Tzong Horng, Jing-Long Huang, Kuo-Wei Yeh, Jia-Jing Gau, Cheng-Wei Chang, Lai-Zhen Zhuang

Abstract

Background: To investigate the association and magnitude of risk between JIA, its associated treatment and cancer development in Taiwanese children.

Methods: Nationwide population-based 1:4 age- and gender-matched retrospective cohort study was designed using the National Health Insurance Research Database of Taiwan. A cohort of 2,892 children <16 years old with JIA was formed as well as a non-JIA cohort of 11,568 in year 2003 to 2005. They were followed up till a diagnosis of malignancy or up to 8 years until 2010. Relative risk (RR), incidence rate ratio (IRR), and adjusted hazard ratio (aHR) of developing malignancy were calculated.

Results: The female to male ratio was 0.79:1. There were 3 cases of incident cancer in the "MTX use, biologics-naïve" group, only 1 in the anti-TNF biologics-containing group and 29 in the "both MTX- and biologics-naïve" group, in comparison, there were 50 cases of cancer in the non-JIA comparator group. During a 16114.16 patient-years follow-up, the RR and IRR for developing a malignancy in both methotrexate- and anti-tumor necrosis factor (TNF) biologics-naïve JIA children were 2.75 (95% confidence interval, 1.75 - 4.32) and 3.21 (2.01 - 5.05), respectively. For leukemia, the IRR was 7.38 (2.50 - 22.75); lymphoma, 8.30 (1.23 - 69.79); and soft tissue sarcoma, 11.07 (0.84 - 326.4). The IRR of other cancers was 2.08 (1.11 - 3.71). The aHR on cancer risk was 3.14 (1.98 - 4.98) in methotrexate- and biologics-naïve group. There were no statistically significant increased risk in JIA patients treated with methotrexate and/or anti-TNF biologics.

Conclusions: Compared with children without JIA, children with JIA have 3-fold increase of risk on malignancy in East Asia. Seemingly neither methotrexate nor anti-TNF biologics increases the risk further.

Figures

Figure 1
Figure 1
Retrospective cohort study design and study flow chart. NHIRD: National Health Insurance Research Database Taiwan; JIA: Juvenile idiopathic arthritis equivalent.

References

    1. 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 classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–392.
    1. Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58(1):15–25. doi: 10.1002/art.23177.
    1. Sacks JJ, Helmick CG, Luo YH, Ilowite NT, Bowyer S. Prevalence of and annual ambulatory health care visits for pediatric arthritis and other rheumatologic conditions in the United States in 2001-2004. Arthritis Rheum. 2007;57(8):1439–1445. doi: 10.1002/art.23087.
    1. Symmons DP, Jones M, Osborne J, Sills J, Southwood TR, Woo P. Pediatric rheumatology in the United Kingdom: data from the British pediatric rheumatology group national diagnostic register. J Rheumatol. 1996;23(11):1975–1980.
    1. Huang JL. New advances in juvenile idiopathic arthritis. Chang Gung Med J. 2012;35(1):1–14.
    1. Huang JL, Yao TC, See LC. Prevalence of pediatric systemic lupus erythematosus and juvenile chronic arthritis in a Chinese population: a nation-wide prospective population-based study in Taiwan. Clin Exp Rheumatol. 2004;22(6):776–780.
    1. Fujikawa S, Okuni M. Clinical analysis of 570 cases with juvenile rheumatoid arthritis: results of a nationwide retrospective survey in Japan. Acta Paediatr Jpn. 1997;39(2):245–249. doi: 10.1111/j.1442-200X.1997.tb03593.x.
    1. Manners PJ, Bower C. Worldwide prevalence of juvenile arthritis why does it vary so much? J Rheumatol. 2002;29(7):1520–1530.
    1. Shen CC, Yeh KW, Ou LS, Yao TC, Chen LC, Huang JL. Clinical features of children with juvenile idiopathic arthritis using the ILAR classification criteria: a community-based cohort study in Taiwan. J Microbiol Immunol Infect. 2013;46(4):288–294. doi: 10.1016/j.jmii.2012.03.006.
    1. Anink J, Otten MH, Prince FH, Hoppenreijs EP, Wulffraat NM, Swart JF, Ten Cate R, van Rossum MA, van den Berg JM, Dolman KM, Koopman-Keemink Y, Armbrust W, Kamphuis S, van Pelt PA, Gorter SL, van Suijlekom-Smit LW. Tumour necrosis factor-blocking agents in persistent oligoarticular juvenile idiopathic arthritis: results from the Dutch arthritis and biologicals in children register. Rheumatology (Oxford) 2013;52(4):712–717. doi: 10.1093/rheumatology/kes373.
    1. Bracaglia C, Buonuomo PS, Tozzi AE, Pardeo M, Nicolai R, Campana A, Insalaco A, Cortis E, de Benedetti F. Safety and efficacy of etanercept in a cohort of patients with juvenile idiopathic arthritis under 4 years of age. J Rheumatol. 2012;39(6):1287–1290. doi: 10.3899/jrheum.111555.
    1. Gutierrez-Suarez R, Burgos-Vargas R. The use of methotrexate in children with rheumatic diseases. Clin Exp Rheumatol. 2010;28(5 Suppl 61):S122–S127.
    1. Kemper AR, Van Mater HA, Coeytaux RR, Williams JW, Jr, Sanders GD. Systematic review of disease-modifying antirheumatic drugs for juvenile idiopathic arthritis. BMC Pediatr. 2012;12:29. doi: 10.1186/1471-2431-12-29.
    1. Lovell J, Giannini H, Reiff A, Cawkwell D, Silverman D, Nocton J, Stein D, Gedalia A, Ilowite T, Wallace A, Whitmore J, Finck BK. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med. 2000;342:763–769. doi: 10.1056/NEJM200003163421103.
    1. Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Martini A, Rabinovich CE, Ruperto N. 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. 2011;63(4):465–482. doi: 10.1002/acr.20460.
    1. Bernatsky S, Rosenberg AM, Oen KG, Duffy CM, Ramsey-Goldman R, Labrecque J, St Pierre Y, Clarke AE. Malignancies in juvenile idiopathic arthritis: a preliminary report. J Rheumatol. 2011;38(4):760–763. doi: 10.3899/jrheum.100711.
    1. Thomas E, Brewster DH, Black RJ, Macfarlane GJ. Risk of malignancy among patients with rheumatic conditions. Int J Cancer. 2000;88(3):497–502. doi: 10.1002/1097-0215(20001101)88:3<497::AID-IJC27>;2-J.
    1. Simard J, Neovius M, Hagelberg S, Askling J. Juvenile idiopathic arthritis and risk of cancer: a nationwide cohort study. Ann Rheum Dis. 2010;69(Suppl 3):81.
    1. 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. 2012;64(9):1357–1364. doi: 10.1002/acr.21709.
    1. Beukelman T, Haynes K, Curtis JR, Xie F, Chen L, Bemrich-Stolz CJ, Delzell E, Saag KG, Solomon DH, Lewis JD. Rates of malignancy associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum. 2012;64(4):1263–1271. doi: 10.1002/art.34348.
    1. Kok VC, Horng JT, Lin HL, Chen YC, Chen YJ, Cheng KF. Gout and subsequent increased risk of cardiovascular mortality in non-diabetics aged 50 and above: a population-based cohort study in Taiwan. BMC Cardiovasc Disord. 2012;12:108. doi: 10.1186/1471-2261-12-108.
    1. Kok VC, Horng JT, Agustriawan D. Statins use increases the risk of urinary tract cancer: preliminary results of a nationwide population-based case-control study. Asia Pac J Clin Oncol. 2012;9(2):190–191. doi: 10.1111/j.1743-7563.2012.01552.x.
    1. Chen TA, Kang HY, Chang HC, Lin WC, Chao TM, Horng JT. Gender differences in colorectal cancer during the past 20 years in Taiwan. Int J Colorectal Dis. 2012;27(3):345–353. doi: 10.1007/s00384-011-1318-1.
    1. Chen TA, Horng JT, Lin WC. Metachronous colorectal cancer in Taiwan: analyzing 20 years of data from Taiwan Cancer Registry. Int J Clin Oncol. 2013;18(2):267–272. doi: 10.1007/s10147-011-0373-5.
    1. Chang CW, Kok VC, Tseng TC, Horng JT, Liu CE. Diabetic patients with severe sepsis admitted to intensive care unit do not fare worse than non-diabetic patients: a nationwide population-based cohort study. PLoS One. 2012;7(12):e50729. doi: 10.1371/journal.pone.0050729.
    1. Yeh KW, Yu CH, Chan PC, Horng JT, Huang JL. Burden of systemic lupus erythematosus in Taiwan: a population-based survey. Rheumatol Int. 2013;33(7):1805–1811. doi: 10.1007/s00296-012-2643-6.
    1. Yu HH, Chen PC, Wang LC, Lee JH, Lin YT, Yang YH, Lin CP, Chiang BL. Juvenile idiopathic arthritis-associated uveitis: a nationwide population-based study in Taiwan. PLoS One. 2013;8(8):e70625. doi: 10.1371/journal.pone.0070625.
    1. Cron R, Beukelman T. Guilt by association - what is the true risk of malignancy in children treated with etanercept for JIA? Pediatr Rheumatol. 2010;8(1):23. doi: 10.1186/1546-0096-8-23.
    1. Diak P, Siegel J, La Grenade L, 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;62:2517–2524. doi: 10.1002/art.27511.
    1. Horneff G, Foeldvari I, Minden K, Moebius D, Hospach T. Report on malignancies in the German juvenile idiopathic arthritis registry. Rheumatology (Oxford) 2011;50(1):230–236. doi: 10.1093/rheumatology/keq361.
    1. Lehman TJA. Should the food and drug administration warning of malignancy in children receiving tumor necrosis factor α blockers change the way we treat children with juvenile idiopathic arthritis? Arthritis Rheum. 2010;62(8):2183–2184. doi: 10.1002/art.27506.
    1. Onel KB, Onel K. Tumor necrosis factor inhibitors and cancer in juvenile idiopathic arthritis: Disentangling the web. Arthritis Rheum. 2012;64(4):966–969. doi: 10.1002/art.34349.
    1. Minden K, Niewerth M, Zink A, Seipelt E, Foeldvari I, Girschick H, Ganser G, Horneff G. Long-term outcome of patients with JIA treated with etanercept, results of the biologic register JuMBO. Rheumatology (Oxford) 2012;51(8):1407–1415. doi: 10.1093/rheumatology/kes019.
    1. Deepak P, Sifuentes H, Sherid M, Stobaugh D, Sadozai Y, Ehrenpreis ED. T-cell non-Hodgkin’s lymphomas reported to the FDA AERS with tumor necrosis factor-alpha (TNF-alpha) inhibitors: results of the REFURBISH study. Am J Gastroenterol. 2013;108(1):99–105. doi: 10.1038/ajg.2012.334.
Pre-publication history
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