Juvenile idiopathic arthritis and risk of cancer: A nationwide cohort study

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 62; no. 12; pp. 3776 - 3782
• Main Authors: Simard, J. F., Neovius, M., Hagelberg, S., Askling, J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2010; Wiley; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Juvenile - complications; Arthritis, Juvenile - drug therapy; Biological and medical sciences; Biological Products - adverse effects; Biological Products - therapeutic use; Cancer; Child; Child, Preschool; Cohort Studies; Confidence intervals; Diseases of the osteoarticular system; Female; Follow-Up Studies; Health risk assessment; Humans; Incidence; Infant; Infant, Newborn; Inflammatory joint diseases; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Neoplasms - chemically induced; Neoplasms - epidemiology; Registries; Regression Analysis; Retrospective Studies; Risk Factors; Sweden - epidemiology; Young Adult; Sweden; Chronic; Cohort study; Diseases of the osteoarticular system; Risk factor; Rheumatology; Juvenile rheumatoid arthritis; Inflammatory joint disease; Malignant tumor; Cancer
• ISSN: 0004-3591; 2326-5191; 1529-0131; 1529-0131; 2326-5205
• DOI: 10.1002/art.27741

Objective Reports of therapy‐related adverse events suggest an elevated rate of malignancy in patients with juvenile idiopathic arthritis (JIA) treated with biologic therapies. However, the scarcity of data on the underlying risk of malignancy in JIA hampers interpretation of these signals. Therefore, the aim of this study was to determine the risk of cancer in patients with JIA as compared with that in the general population. Methods Through linkage with a national database, the Swedish Patient Register (comprising inpatient discharges in 1969–2007 and specialist outpatient visits in 2001–2007 in Sweden), a national JIA cohort (n = 9,027) was identified, and each JIA case was matched with 5 general population comparators. Using data from the Swedish Cancer, Census, Death, and Biologics Registers, the occurrence of cancer, vital status, and start of a biologic therapy were identified. The relative risk (RR) of first occurrence of a primary cancer in patients who had not been treated with biologics (biologics‐naive patients with JIA) was estimated using Poisson regression, stratified a priori by year of earliest identification of JIA (before 1987 versus 1987 and thereafter). In sensitivity analyses, the data were followed up to 1999, when biologics first became available. Results In this biologics‐naive JIA cohort, 60 malignancies were observed during 131,144 person‐years of followup, compared with 266 cancers observed during 661,758 person‐years in the general population comparator (0.46 cases/1,000 person‐years versus 0.40 cases/1,000 person‐years; RR 1.1, 95% confidence interval [95% CI] 0.9–1.5). Patients with JIA identified before 1987 were not at increased risk of cancer, whereas JIA identified in 1987 and thereafter was significantly associated with incident lymphoproliferative malignancies (RR 4.2, 95% CI 1.7–10.7) and cancers overall (RR 2.3, 95% CI 1.2–4.4). Sensitivity analyses did not reveal any ready explanation for this heterogeneity. Conclusion Although absolute risks were low, an elevated risk of malignancy was observed among biologics‐naive patients in whom the diagnosis of JIA was made in the past 20 years, which may have implications for the interpretation of cancer signals in patients with JIA treated with newer therapies.