Spotlight on Research 2010

November 2010 (historical)

Highlights of Current NIAMS Pediatric Rheumatology Research

The NIAMS supports a broad portfolio of projects related to rheumatic diseases in children. According to a 2008 report from the National Arthritis Data Workgroup, about 294,000 children are affected with arthritis or other rheumatic conditions. The following is a representative sample of the studies NIAMS is currently funding for pediatric rheumatology.

CARRA (Childhood Arthritis and Rheumatology Research Alliance). CARRA is a multi-center network of pediatric rheumatology research centers across North America that are working together on a variety of research studies in children with rheumatic diseases. Such collaboration increases the number of children who participate in studies and reduces the research time it takes to reach valuable conclusions. CARRA includes a number of research projects:

CARRA: Accelerating Toward an Evidence-Based Culture in Pediatric Rheumatology

Principal Investigator: Laura Schanberg, M.D. (Duke University, Durham, NC)

Goal of the study: To rapidly transform the culture of pediatric rheumatology toward universal participation in research.

Description of the study: CARRA is seeking to develop an evidence-based approach to the care of children with rheumatic diseases. To that end, this project is collecting data from a large group of children with rheumatic diseases (including lupus, juvenile arthritis, scleroderma, and others) at CARRA centers nationwide. The data will be used in an informatics platform that will be available to pediatric rheumatologists throughout the U.S. The collection and distribution of such disease data are crucial to the understanding of these diseases and the development of new treatments for them. CARRA is also developing a network of translational research laboratories to facilitate the discovery of biomarkers for rheumatic disease in children and an understanding of how these diseases develop and progress. This project is being funded through the American Recovery and Reinvestment Act (ARRA).

Efficacy Measures for Pediatric Lupus Studies

Principal Investigator: Hermine Brunner, M.D., M.Sc. (Cincinnati Children’s Medical Center, Cincinnati, OH)

Goal of the study: To develop outcome measures for pediatric lupus that will be used to measure disease flares and remissions.

Description of the study: Without specific outcome measures, the testing of new drugs for childhood lupus is very difficult. The researchers are working to develop measures that will advance biomarker discovery, promote translational research, and facilitate clinical trials to test the efficacy of new drugs for pediatric lupus. The collected data will serve as the foundation for a CARRA Pediatric Lupus Registry. A versatile Web-based Lupus Study Management System will also be developed and made available to the pediatric rheumatology community. Well-defined flare and remission criteria will provide the data needed for clinical trials of the most potent new medications that are currently being developed.

Comparative Effectiveness Research in Pediatric Rheumatic Diseases

Principal Investigator: Carol A. Wallace, M.D. (Children’s Hospital and Regional Medical Center, Seattle, WA).

Goal of the study: To develop a platform for comparative effectiveness research in pediatric rheumatic diseases.

Description of the study: The study of rheumatic diseases in children has been hampered in the past by the heterogeneity of the conditions (they can look very different in different children) and an incomplete understanding of how the diseases develop and progress. This project seeks to tap into the network structure of CARRA and its large cohort of patients to create a pediatric rheumatology registry. This registry will collect data on demographics, disease features, treatments, laboratory and radiology results, and other data in order to compare the effectiveness of various approaches to treating these diseases. This project is being funded through the ARRA.

Pediatric Rheumatology Research Scientific Meeting

Principal Investigator: Christy Sandborg, M.D., (Stanford University, Stanford, CA)

Goal of the project: This annual meeting offers CARRA members the opportunity to collaborate‚ network‚ and break into small workgroups to discuss past‚ ongoing and future studies.

Description of the project: NIAMS is providing funds for the annual pediatric rheumatology scientific meeting co-sponsored by CARRA. The main objective of the meeting is to discuss which research projects should be pursued in the coming year and to share results of past research. The 2010 meeting was held April 23-25 in Chicago, and focused on the development of consensus treatment plans in four disease-specific work groups: juvenile idiopathic arthritis, localized scleroderma, juvenile dermatomyositis, and juvenile lupus. Using results from CARRA research, the groups developed disease criteria, clinical assessment measures, and other elements of comprehensive, evidence-based treatment plans for these diseases.

NIAMS also supports the following projects in pediatric rheumatology which are not included in CARRA:

Gene Expression in Pediatric Arthritis

Principal Investigator: David N. Glass, M.D. (Cincinnati Children’s Medical Center, Cincinnati, OH)

Goal of the project: To detect differential expression of genes in children with pediatric rheumatic diseases.

Description of the project: Rapid advances in biotechnology have created an unprecedented opportunity to refine the diagnosis, treatment, and understanding of pediatric rheumatic diseases. Four separate projects will focus on identifying the specific gene expressions involved in these diseases and how those gene expressions change with disease progression and treatment.

Pediatric Rheumatology Training Grants:

Principal Investigators: Thomas Griffin, M.D., Ph.D. (University of Cincinnati, Cincinnati, OH) and Raphael Hirsch, M.D. (University of Pittsburgh, Pittsburgh, PA)

Goal of the project: To educate a new generation of academic pediatric rheumatologists who can play leading roles as physician-scientists and help to address the nationwide shortage of physicians who treat children with rheumatic diseases.

Description of the project: These programs seek to provide the research role models, mentorship, and rich environment necessary for nurturing cutting-edge pediatric rheumatologists and ensuring their success. NIAMS also supports a number of grants for training physicians in both adult and pediatric rheumatology research.

Cincinnati Multidisciplinary Clinical Research Center

Principal Investigator: Daniel Lovell, M.D., M.P.H. (Cincinnati Children’s Medical Center, Cincinnati, OH)

Goal of the project: This center's chief focus is a greater understanding of the mechanisms of the rheumatic illnesses of childhood and their treatment.

Description of the project: Four projects are included under this center: magnetic resonance imaging for pediatric neuro-psychiatric lupus; improved understanding of the biology and use of tumor necrosis factor inhibition in juvenile idiopathic arthritis (JIA); biomarkers of macrophage activation syndrome (MAS, a potentially life-threatening complication) in systemic JIA; and a study of the determinants of health-related quality of life in children with JIA.

Genetics of Juvenile Idiopathic Arthritis and Subtypes

Principal Investigator: Carl D. Langefeld, Ph.D. (Wake Forest University, Winston-Salem, NC)

Goal of the project: To identify genetic factors of JIA.

Description of the project: The researchers are analyzing existing genome-wide association (GWA) data on 800 JIA cases and more than 3,000 controls of European ancestry. These analyses will assist in the long-term goal of understanding JIA, while recognizing the diversity of conditions included in JIA. This may lead to advances in the diagnosis, prognosis, and treatment of the disease.

NIAMS Intramural Research

Through its Intramural Research Program (IRP), NIAMS continues to support the NIH Pediatric Rheumatology Clinic, a specialty-care medical facility dedicated to evaluating and treating children with pediatric rheumatic diseases.

NIAMS researchers working in the NIH Pediatric Rheumatology Clinic are studying the genetics of periodic fever syndromes and other rheumatic diseases in children and training physicians in pediatric rheumatology. Through the work of the clinic, researchers were able to identify a new autoinflammatory syndrome, DIRA (deficiency of the interleukin-1 receptor antagonist, or IL-1Ra) and treat it successfully using anakinra, a synthetic form of human IL-1Ra. Clinical protocols in the NIAMS IRP include trials of canakinumab and anakinra in children with autoinflammatory diseases, as well as studies of the pathogenesis and natural history of autoinflammatory diseases and arthritis.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

More information about the National Institutes of Health’s American Recovery and Reinvestment Act (ARRA) grant funding opportunities can be found at http://grants.nih.gov/recovery/. To track the progress of HHS activities funded through the ARRA, visit www.hhs.gov/recovery. To track all federal funds provided through the ARRA, visit www.recovery.gov.