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

BMC Cancer

Victor C Kok³  Jorng-Tzong Horng⁴  Jing-Long Huang⁵  Kuo-Wei Yeh²  Jia-Jing Gau⁴  Cheng-Wei Chang¹  Lai-Zhen Zhuang⁴ 

[1] Department of Information Management, Hsing Wu University, New Taipei City, Taiwan

[2] Division of Paediatric Allergy Asthma and Rheumatology, Department of Paediatrics, Chang Gung Memorial Hospital, Linkou, Taiwan

[3] Division of Medical Oncology, Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan

[4] Department of Computer Science and Information Engineering, National Central University, Chungli, Taiwan

[5] Chang Gung University College of Medicine, Taoyuan, Taiwan

关键词: Cohort studies (MeSH);    Risk (MeSH);    Neoplasms (MeSH);    Juvenile idiopathic arthritis;    Juvenile rheumatoid (MeSH);    Arthritis;   

Others  :  1121196
DOI  :  10.1186/1471-2407-14-634

 received in 2014-02-16, accepted in 2014-08-21,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Kok et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [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.
• [2]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.
• [3]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.
• [4]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.
• [5]Huang JL: New advances in juvenile idiopathic arthritis. Chang Gung Med J 2012, 35(1):1-14.
• [6]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.
• [7]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.
• [8]Manners PJ, Bower C: Worldwide prevalence of juvenile arthritis why does it vary so much? J Rheumatol 2002, 29(7):1520-1530.
• [9]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.
• [10]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.
• [11]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.
• [12]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.
• [13]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. BioMed Central Full Text
• [14]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.
• [15]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.
• [16]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.
• [17]Thomas E, Brewster DH, Black RJ, Macfarlane GJ: Risk of malignancy among patients with rheumatic conditions. Int J Cancer 2000, 88(3):497-502.
• [18]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.
• [19]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.
• [20]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.
• [21]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. BioMed Central Full Text
• [22]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.
• [23]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.
• [24]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.
• [25]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.
• [26]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.
• [27]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.
• [28]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. BioMed Central Full Text
• [29]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.
• [30]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.
• [31]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.
• [32]Onel KB, Onel K: Tumor necrosis factor inhibitors and cancer in juvenile idiopathic arthritis: Disentangling the web. Arthritis Rheum 2012, 64(4):966-969.
• [33]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.
• [34]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.