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

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-naive" group, only 1 in the anti-TNF biologics-containing group and 29 in the "both MTX-and biologics-naive" 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-naive 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-naive 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.