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Cancer rate 4 times higher in children with juvenile arthritis

Increase not necessarily linked to arthritis treatments, including TNF inhibitors

New research reports that incident malignancy among children with juvenile idiopathic arthritis (JIA) is four times higher than in those without the disease. Findings now available in Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology (ACR), suggest JIA treatment, such as tumor necrosis factor (TNF) inhibitors, does not necessarily explain the development of cancer in this pediatric population.

Children with JIA experience symptoms similar to adults with arthritis including joint pain, swelling, tenderness and stiffness. JIA is a general term used to describe the various chronic arthritis diseases in children and affects roughly 294,000 under the age of 17 in the U.S. according to a 2008 report from the National Arthritis Data Workgroup.

One of the drug types used to treat childhood and adult arthritis, along with a number of other rheumatic conditions, is TNF inhibitors. Studies have reported that more than 600,000 people worldwide have received anti-TNF therapy since their introduction 15 years ago. However, possible cancer risk has been associated with treatment, prompting the U.S. Food and Drug Administration (FDA) to place "black box" warnings of the potential malignancy risk on TNF inhibitors labels.

In the present study Dr. Timothy Beukelman from the University of Alabama at Birmingham and colleagues conducted one of the largest investigations into the rates of incident malignancy among JIA pediatric patients relative to their treatment. Using data from the U.S. Medicaid records from 2000 through 2005, researchers identified 7,812 children with JIA and two comparator groups without JIA; one group with asthma (652,234 children) and the second with attention-deficit hyperactivity disorder (ADHD; 321,821 children).

The team categorized patients' treatment with methotrexate and TNF inhibitors as "ever" or "never" used, though many children with JIA did not receive either of these treatments during the study. The research team did not have access to detailed medical records, and therefore categorized the identified incident malignancies as "possible," "probable," or "highly probable."

Children diagnosed with JIA had a total follow-up time of 12,614 person-years with 1,484 children in this group contributing 2,922 person-years of anti-TNF exposure. The team determined that among all children with JIA compared to those without JIA, the incidence rate was 4.4 times higher for probable and highly probable malignancies. Pediatric JIA patients treated with methotrexate without TNF inhibitors had a similarly increased incidence of cancer, which was 3.9 times higher than children without JIA. No probable or highly probable malignancies were identified in patients following any use of anti-TNF during the study period.

In a related editorial published today in Arthritis & Rheumatism, Dr. Karen B. Onel and Dr. Kenan Onel from the University of Chicago state that the Beukelman et al. study indicates that children with JIA may be at increased cancer risk from the disease, but suggests that anti-TNF therapy may not be associated with a further increased cancer risk. Dr. Kenan Onel cautions, "Larger studies in different populations and with longer follow up are required to confirm Dr. Beukelman's findings."

The editorial authors point out that most patients in this study were treated with etanercept, a soluble TNF receptor blocker, and the investigation of other anti-TNF agents working by different mechanisms may yield different results. Nonetheless, Dr. Onel argues, "By focusing on the possible cancer risk associated with the use of TNF inhibitors, the underlying cancer risk associated with JIA may have been understated, and it is important to make patients, families, and physicians aware of the possible late consequences of this disease."

Dr. Beukelman concludes, "While our findings show children with JIA have a higher incidence of cancer compared to peers without JIA, the greater frequency of malignancy does not appear to be necessarily associated with treatment, including use of TNF inhibitors. This highlights the critical importance of appropriate comparator groups when evaluating the safety of new medications. Further confirmation of our findings with large-scale and long-term investigation of the association between cancer and JIA, and its treatment is needed."

This research was supported by grants from the Agency for Healthcare Research and Quality (AHRQ), the Food and Drug Administration (FDA) U.S. Department of Health and Human Services (DHHS), and the National Institutes of Health (NIH).

This study is published in Arthritis & Rheumatism. Media wishing to receive a PDF of this article may contact

Full citations: "Rates of Malignancy Associated with Juvenile Idiopathic Arthritis and Its Treatment." Timothy Beukelman, Kevin Haynes, Jeffrey R Curtis, Fenglong Xie, Lang Chen, Christina J. Bemrich-Stolz, Elizabeth Delzell, Kenneth G Saag, Daniel H Solomon, James D Lewis on behalf of the Safety Assessment of Biological thERapeutics (SABER) Collaboration. Arthritis & Rheumatism; Published Online: February 13, 2012 (DOI: 10.1002/art.34348).

URL Upon publication:

Editorial: "TNF inhibitors and Cancer in JIA: Disentangling the Web." Karen B Onel and Kenan Onel. Arthritis & Rheumatism; Published Online: February 13, 2012 (DOI: 10.1002/art.34349).

URL Upon publication:

Author Contacts: To arrange an interview with Dr. Beukelman, please contact Bob Shepard with the University of Alabama at Birmingham at . Media wishing to speak with Dr. Karen B. Onel or Dr. Kenan Onel may contact John Easton with the University of Chicago Medical Center at .

About the Journal:

Arthritis & Rheumatism is an official journal of the American College of Rheumatology (ACR) and the Association of Rheumatology Health Professionals (ARHP), a division of the College, and covers all aspects of inflammatory disease. The American College of Rheumatology ( is the professional organization who share a dedication to healing, preventing disability, and curing the more than 100 types of arthritis and related disabling and sometimes fatal disorders of the joints, muscles, and bones. Members include practicing physicians, research scientists, nurses, physical and occupational therapists, psychologists, and social workers. The journal is published by Wiley-Blackwell on behalf of the ACR. For more information, please visit
About Wiley-Blackwell:

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit or our new online platform, Wiley Online Library (, one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

Dawn Peters | EurekAlert!
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