Newswise — Children with juvenile idiopathic arthritis have a two to threefold increased risk of developing cancer compared to similarly-aged children without JIA, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta. The same study also reported no cases of cancer in children with JIA who were exposed to anti-TNF therapy.
TNF antagonists, also called biologics or anti-TNF therapy, are a class of drugs that have been used since 1998; overall, they have been given to more than 600,000 people worldwide. These drugs are given by injection and lessen inflammation by interfering with biologic substances that cause or worsen the inflammatory process.
"These findings are likely to mitigate concern that arose in 2009 after a study by the Food and Drug Administration raised the possibility that children treated with anti-TNF therapy had an increased risk of developing malignancy compared to children in the general population," says Timothy Beukelman, MD, MSCE, assistant professor of pediatrics in the Division of Pediatric Rheumatology at the University of Alabama at Birmingham and lead investigator in the study. “This study led the FDA to issue a "black box" warning regarding the risk of pediatric malignancy for all of the anti-TNF agents,” he says.
About one child in every 1,000 develops some type of juvenile arthritis. These disorders can affect children at any age, although rarely in the first six months of life. It is estimated that around 300,000 children in the U.S. have been diagnosed with JIA. There are several types of JIA, all involving chronic (long-term) joint inflammation. This inflammation begins before patients reach the age of 16, may involve one or many joints, and can cause other symptoms such as fevers, rash and/or eye inflammation and even cause inflammation of the internal organs.
Dr. Beukelman’s research team recently used National Medicaid Administrative Claims data from all 50 U.S. states—collected between 2000 and 2005—to identify 7,321 children with JIA confirmed by both a doctor’s diagnosis and based on taking medications used to treat the disease. Among these children, 3,194 were taking methotrexate, a disease-modifying antirheumatic drug, and 1,413 were exposed to TNF antagonists.
The rate of cancer among all children with JIA was approximately 59 per 100,000 person-years (number of patients multiplied by number of years of observation). By comparison, the standardized rates of cancer in two groups of children without JIA were approximately 23 to 27 per 100,000 person years. Researchers identified no malignancies in participants with JIA who had been exposed to anti-TNF therapy, though the number of children treated was relatively small.
“I believe that many people agree that there’s increased risk [of malignancy in JIA patients], but it’s not all attributable to TNF inhibitors. At least part of the increased risk, and perhaps even all of it, appears to be attributable to the disease itself,” says Dr. Beukelman.
There have been few studies investigating the relationship between JIA and cancer. However, efforts to establish the background risk of cancer associated with JIA have increased since the FDA issued its findings that TNF inhibitors are associated with an increased risk of cancer. Efforts are also underway to prospectively collect data on all children who are exposed to TNF inhibitors.
“How disease activity in JIA influences the risk of cancer is not known. We did not have access to that kind of clinical information in this type of administrative database,” Dr. Beukelman explains. “TNF inhibitors may possibly be associated with an increased risk of cancer; our study did not have enough patients to definitively answer this question. But based on our findings, the amount of risk that the TNF inhibitors may be responsible for appears to be much smaller than initially suspected.”
The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on twitter by using the official hashtag: #ACR2010.
###Editor’s Notes: Timothy Beukelman, MD, MSCE will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 11:15 AM on Wednesday, November 10 in the Hall A3. Dr. Beukelman will be available for media questions and briefing at 8:30 AM on Tuesday, November 9 in the on-site press conference room, B 212.
Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Presentation Number: 2084
Rates of Malignancy Associated with Juvenile Idiopathic Arthritis and Its Treatment: An Observational Study of National U.S. Medicaid Administrative Claims Data.
Timothy Beukelman, MD, MSCE (Pediatric Rheumatology, University of Alabama-Birmingham, Birmingham, AL)Kevin Haynes (Univ of Pennsylvania)Jeffrey R Curtis, MD, MPH (Rheumatology & Immunology, University of AL Birmingham, Birmingham, AL)Fenglong Xie (Univ of Alabama at Birmingham)Lang Chen (Univ of Alabama at Birmingham)Elizabeth Delzell (Univ of Alabama at Birmingham)Hopiy Kim (Univ of Pennsylvania)Kenneth G Saag, MD, MSc (Division Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL)James D Lewis (Univ of Pennsylvania)
Background: A possible increased risk of malignancy in children with juvenile idiopathic arthritis (JIA), particularly in those receiving treatment with tumor necrosis factor alpha inhibitors (anti-TNF) has been reported. We analyzed national Medicaid administrative claims data to determine standardized rates of malignancy among children with JIA.
Methods: Using Medicaid data from all 50 U.S. states from 2000 through 2005, we identified a cohort of children with JIA based on physician diagnosis codes and dispensed medication prescriptions. We identified non-JIA control cohorts of children diagnosed with asthma and attention deficit hyperactivity disorder (ADHD). Subjects were excluded if they had any physician diagnosis code for malignancy prior to study entry. All subjects had a minimum 9 month baseline assessment period prior to study entry in which to identify prevalent malignancies. For all subjects this baseline assessment period included at least 3 months subsequent to satisfying the disease cohort definitions in order to identify potential incident cancers that were initially misdiagnosed as JIA. Exposure to methotrexate (MTX) and anti-TNF was determined based on dispensed medication prescriptions. Exposed subjects were considered forever exposed and all follow-up time was categorized into 3 groups: (1) no MTX and no anti-TNF; (2) any MTX and no anti-TNF; (3) any anti-TNF. Subjects could contribute follow-up time to more than 1 exposure category sequentially. Malignancy outcomes were defined using physician diagnosis codes, medication codes, and procedure codes using an extension of a previously validated algorithm. Follow-up was censored at loss to follow-up, malignancy outcome, and study end. We calculated crude incidence rates for all malignancies and lymphoma/leukemia for all study groups. Crude rates were standardized to the age, sex, and race distribution of the overall JIA cohort.
Results: The JIA cohort included 7,321 subjects with a median follow-up study time of 1.1 years. Among the JIA subjects, 3,194 were exposed to MTX and 1,413 were exposed to anti-TNF. The asthma (N = 623,663) and ADHD (N = 308,454) cohorts had median follow-up study times of 0.7 and 0.9 years, respectively. Malignancies were identified in 183, 63, and less than 11 patients with asthma, ADHD, and JIA respectively. Crude and standardized rates for all malignancies and for lymphoma/leukemia are shown in the Table. The standardized malignancy rates for JIA were 2 to 3-fold higher than those for ADHD and asthma. No cases of malignancy were identified in JIA subjects who had been exposed to anti-TNF. Conclusions: Children diagnosed with JIA, irrespective of MTX use, appeared to have an increased risk of malignancy compared to children with asthma and ADHD. There were no cases of malignancy identified in more than 2,700 person-years of anti-TNF exposure in more than 1,400 subjects with JIA.
Disclosure: Timothy Beukelman, nothing to disclose; Kevin Haynes, nothing to disclose; Jeffrey Curtis, Amgen Inc.: Research grants, Centocor, Inc.: Research grants, Consulting fees, Corrona: Research grants, Consulting fees, Roche: Research grants, Consulting fees, Speakers' bureau, UCB, Inc.: Consulting fees, Speakers' bureau; Fenglong Xie, nothing to disclose; Lang Chen, nothing to disclose; Elizabeth Delzell, Amgen Inc.: Research grants; Hopiy Kim, nothing to disclose; Kenneth Saag: Amgen Inc.: Research grants, Consulting fees, Speakers' bureau, AstraZeneca: Consulting fees, Eli Lilly and Company: Research grants, Consulting fees, Genentech and Biogen IDEC Inc: Consulting fees, GlaxoSmithKline: Research grants, Consulting fees, Merck Pharmaceuticals: Research grants, Consulting fees, NicOx: Consulting fees, Nitec: Consulting fees, Novartis Pharmaceuticals Corporation: Research grants, Consulting fees, Speakers' bureau, Pfizer Inc: Consulting fees, Proctor & Gamble Pharmaceuticals: Research grants, Roche: Research grants, Takeda Pharmaceuticals North America: Consulting fees, UCB, Inc.: Consulting fees; James Lewis, Amgen Inc.: Consulting fees, AstraZeneca: Consulting fees, Centocor, Inc.: Research grants, GlaxoSmithKline: Consulting fees, Millenium Pharmaceuticals: Consulting fees, Shire: Research grants, Roche: Consulting fees, Takeda Pharmaceuticals North America: Research grants.
View press release with full abstract at www.rheumatology.org
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