Rates of malignancy associated with juvenile idiopathic arthritis and its treatment

Arthritis Rheum. 2012 Apr;64(4):1263-71. doi: 10.1002/art.34348. Epub 2012 Feb 10.


Objective: To determine the relative rates of incident malignancy among children with juvenile idiopathic arthritis (JIA) with respect to treatment as compared to children without JIA.

Methods: Using national Medicaid data from 2000 through 2005, we identified cohorts of children with JIA and without JIA according to the diagnosis codes used by their physicians and the medication prescriptions that were dispensed. Study followup began after a 6-month lag period to exclude prevalent and misdiagnosed malignancies. Treatment with methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors was categorized as ever exposed or never exposed. Malignancy outcomes were identified using an adapted version of a previously validated algorithm. Incident malignancies were categorized as possible, probable, or highly probable based on a comprehensive review of all claims. Malignancy rates were standardized to the age, sex, and race distribution of the overall JIA cohort. Standardized incidence ratios (SIRs) were calculated using children with attention deficit hyperactivity disorder (n = 321,821) (one of two comparator groups included) as the referent group.

Results: The JIA cohort included 7,812 children with a total followup time of 12,614 person-years; 1,484 of these children contributed 2,922 person-years of TNF inhibitor exposure. For all children with JIA versus children without JIA, the SIR was 4.4 (95% confidence interval [95% CI] 1.8-9.0) for probable and highly probable malignancies. For those taking MTX without TNF inhibitor use, the SIR was 3.9 (95% CI 0.4-14). Following any use of TNF inhibitors, no probable or highly probable malignancies were identified (SIR 0 [95% CI 0-9.7]).

Conclusion: Children with JIA appeared to have an increased rate of incident malignancy compared to children without JIA. The treatment for JIA, including TNF inhibitors, did not appear to be significantly associated with the development of malignancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Juvenile / complications*
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / epidemiology
  • Child
  • Female
  • Humans
  • Incidence
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Neoplasms / epidemiology*
  • Neoplasms / etiology*
  • Prevalence
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Methotrexate