(All fields required)
Please enter a valid email.
Please enter your name.
Daniel J. Lovell, MD, MPH, Principal Investigator
Current treatment approaches for children with JIA result in up to 50 percent of patients demonstrating clinically inactive disease while on treatment. Much of this success is due to the introduction of anti-tumor necrosis factor (anti-TNF) biologic therapies.
Unfortunately, more than 50 percent of the children with clinically inactive disease for periods of three to 12 months while on treatment will demonstrate an obvious and clinically important worsening of the disease within three to 12 months following treatment withdrawal. In addition, anti-TNF therapy is expensive and has been shown to have short- and medium-term toxicities in children with JIA. Current testing cannot predict which children with JIA will experience disease flares after treatment withdrawal.
Our study intends to develop a method (or methods) of using biomarkers to accurately identify patients in whom anti-TNF therapy can be effectively stopped. The study has three specific aims:
This project will use a tiered approach in research design. The first two aims will investigate specific hypotheses about markers that may be used to identify patients in whom anti-TNF therapies can be effectively stopped. Both hypotheses already have strong theoretical support and / or support from preliminary data; consequently, we believe it likely that they will be proven correct.
The third aim uses a gene expression approach to identify additional markers that may be used to identify candidate genes for stopping therapy. Although this aim is more discovery-oriented than focused on testing a specific hypothesis, we believe it has great potential to identify important new biomarkers.
If successful, this study will provide better understanding of the effect of TNF antagonist therapy on the biology of JIA, and could allow safer and more cost effective use of these profoundly important new therapies.
Alexi A. Grom, MD, Principal Investigator
Macrophage activation syndrome (MAS) is a potentially fatal complication for children with systemic JIA (sJIA). It is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic macrophages. Complicating matters, the diagnosis is difficult due to the lack of diagnostic criteria.
This project seeks to understand the pathways leading to the increased incidence of MAS in patients with sJIA, define the MAS risk group, and to develop guidelines for monitoring and treatment of these patients. The project has three specific aims:
Hinze CH, Fall N, Thornton S, Griffin TA, Thompson SD, Colbert RA, Glass DN, Michael G, Barnes BG, Grom AA. Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis. Arthritis Res Ther. 2010.
Vastert SJ, Kuis W, Grom AA. Systemic JIA: new developments in the understanding of the pathophysiology and therapy. Best Pract Res Clin Rheumatol 23:655-64. 2009.
Hazen MM, Woodward AL, Hofman I, Degar BA, Grom AA, Filipovich AH, Binstadt BA. Mutations of the hemophagocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. Arthritis Rheum. 58:567-70. 2008.
Zhang K, Biroscak J, Glass DN, Thompson S, Finkel T, Murray P, Binstadt B, Filipovich A, Grom AA. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 58:2892-6. 2008.
Other Significant Publications
Bleesing J, Prada E, Siegel DM, Villanueva J, Olson J, Ilowite N, Brunner HI, Griffin T, Graham TB, Sherry DD, Passo MH, Filipovich A, Grom AA. The Diagnostic Significance of soluble CD163 and soluble IL2Rα chains in Macrophage Activation Syndrome and Untreated New Onset Systemic Juvenile Idiopathic Arthritis. Arthritis Rheum. 56:965-71. 2007.
Hermine Brunner, MD, Principal Investigator
Although research shows that thinking and memory are affected by lupus, there is currently no way to test for this complication, known as neuropsychiatric lupus (NPSLE), in the clinical setting. This study is employing magnetic resonance imaging to explore how NPSLE affects the nervous system and aims to produce a clinic-useable screening tool for NPSLE.
This project has three specific aims:
Preliminary results from functional MRI scanning show abnormalities even in children with pediatric lupus who do not have NPSLE. Additionally, preliminary testing suggests that Ped-ANAM performance is markedly different in patients with NPSLE versus pediatric lupus patients with normal cognition.
Michael Seid, PhD, Principal Investigator
Health-related quality of life (HRQOL), an individual’s perceptions of his or her physical, psychosocial and role functioning with respect to his or her health, is a key outcome in clinical care of, and clinical trials for, children with juvenile idiopathic arthritis (JIA). Implicit in the measurement of HRQOL as a JIA outcome is the notion that medical interventions, such as drug therapies, can affect not only clinical parameters but also more distal outcomes, such as HRQOL. While much research has focused on understanding how biological and physiological variables affect disease outcomes, far less is known about how changes in clinical parameters are related to improvement in HRQOL.
Our preliminary data suggest that, even with excellent disease control through the use of biologic medications, about half of children with polyarticular arthritis will continue to have a lower quality of life than healthy children. Without a thorough understanding of the determinants of HRQOL and identification of potential modifiers, many children with JIA, even those treated with biologics who have well-controlled arthritis, will continue to experience suboptimal HRQOL. This study’s long-term goal, then, is to improve HRQOL for children with JIA.
Our central hypothesis is that HRQOL is determined only in part by medical parameters, and that non-medical parameters have both direct and indirect effects on the HRQOL of children with JIA. Preliminary analysis of our data suggests that there is an association between medical parameters and HRQOL in the context of treatment, but there is substantial unexplained variance in HRQOL for children with well-controlled arthritis and for children with polyarticular JIA treated for 12 months with biologics.
We will perform a prospective longitudinal cohort study to test our central hypothesis. We will recruit current patients in treatment for six months or less, as well as new patients, and will collect survey data semiannually, for a total of three assessments (baseline, six months and 12 months). This research has two specific aims:
This study represents a novel approach to understanding how clinical parameters and treatment affect HRQOL in children with JIA. It is the first prospective study of HRQOL determinants in this population. Our hope is that this project will lead to a thorough understanding of the main medical and non-medical drivers of HRQOL in children with JIA, thus providing foundational knowledge to develop therapeutic interventions aimed at improving HRQOL.
Seid M, Opipari L, Huang B, Brunner HI, Lovell DJ. Disease control and health-related quality of life in juvenile idiopathic arthritis. Arthritis Rheum. 61(3):393-9. Mar 15, 2009.
3333 Burnet Avenue, Cincinnati, Ohio 45229-3026 | 1-513-636-4200 | 1-800-344-2462 | TTY: 1-513-636-4900
New to Cincinnati Children’s or live outside of the Tristate area? 1-877-881-8479
© 1999-2015 Cincinnati Children's Hospital Medical Center