Rates of malignancy associated with juvenile idiopathic arthritis and its treatment

Abstract

Objective To determine relative rates of incident malignancy among children with juvenile idiopathic arthritis (JIA) with respect to treatment compared to children without JIA Methods Using national U.S. Medicaid data from 2000 through 2005, we identified cohorts of children with JIA and without JIA using physician diagnosis codes and dispensed medication prescriptions. Study follow-up began after a 6 month lag period to exclude prevalent and misdiagnosed malignancies. Treatment with methotrexate and TNF inhibitors was categorized as ever 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 (SIR) were calculated using children without JIA (N=321,821) as the referent group. Results The JIA cohort included 7,812 children with a total follow-up time of 12,614 person-years, of whom 1,484 children contributed 2,922 person-years of TNF inhibitor exposure. For all children with JIA versus children without JIA, the SIR was 4.4 (1.8–9.0) for probable and highly probable malignancies. For methotrexate users without TNF inhibitor use, the SIR was 3.9 (0.4–14). Following any use of TNF inhibitors, no probable or highly probable malignancies were identified (SIR 0 (0–9.7)). Conclusions Children with JIA appeared to have an increased rate of incident malignancy compared to children without JIA. JIA treatment, including TNF inhibitors, did not appear significantly associated with the development of malignancy.

Using Registries to Identify Adverse Events in Rheumatic Diseases

“…Most children are exposed to multiple agents over time, such that pinpointing adverse event association with a single product is problematic. Lastly, as previously described, having rheumatic diseases may predispose children to increased risks for adverse events irrespective of therapy, 6,24 although the magnitude of this baseline risk is poorly quantified.…”

“…Subsequent studies have demonstrated an increased baseline rate of malignancy among all children who have juvenile idiopathic arthritis (JIA) compared with the general population even without biologic exposure. [6][7][8]9 However, other studies have not revealed increased malignancy risk in JIA, highlighting the need for more robust longer-term studies with active comparators rather than historical controls. 10 Other events of interest in children treated with immunomodulatory products include opportunistic infections, lupus or lupuslike illnesses, demyelinating diseases, pulmonary hypertension, inflammatory bowel disease, and uveitis.…”

Long-Term Safety of Immunomodulators in Pediatric Inflammatory Diseases

“…The authors found an increased incidence of malignancy among children with JIA compared with unaffected children (SIR 4.4; 95 % CI 1.8-9.0), but, when patients were divided according to exposure to biologics or methotrexate, treatment did not appear to be significantly associated with the development of malignancy [25].…”

“…Indeed, medications that are used to treat JIA suppress the immune system, potentially increasing the risk of selected malignancies, but a disease-related increased risk of malignancies among children has also been suggested [25].…”

Safety and Efficacy of High-dose Tumor Necrosis Factor (TNF) Inhibitors in the Management of Pediatric Inflammatory Diseases

“…In regard to the safety of biologics, there have been increasing data on long-term outcomes, with reassuring findings reported in several studies [5,[10][11][12][13]. However, the safety and efficacy of higher dose biologics for pediatric patients with a diversity of diseases have not been reported.…”