Grants & Funding

2021 CARRA-Arthritis Foundation Fall Grant Awardees

 

 

Congratulations to the 2021 Fall Grant Cycle Awardees!

 

Health Equity Research Grant Recipients

 

 

 Joyce Chang, MD, MSCE

 Boston Children's Hospital

 

 

 

Project Title: "The Roles of Race, Racism and Neighborhood Health in Outcomes of Pediatric Lupus"

Project Period: July 1, 2021 to June 30, 2022

Lay Summary: Although children with lupus fare better now than they did 10-20 years ago, racial and ethnic minorities with childhood lupus continue to have worse health outcomes compared to their white peers. The neighborhoods in which these children live can have a deep impact on their opportunity to achieve optimal health and wellbeing. Racial residential segregation can perpetuate poor neighborhood conditions, which may contribute to even greater racial disparities in childhood lupus outcomes in certain places. This project will utilize a placebased approach to study whether different dimensions of residential segregation and neighborhood-based opportunity can be used to identify children at the highest risk for poor lupus outcomes. These measures could be employed at the provider, hospital or policy level to determine where and to whom additional services or community interventions should be directed in order to reduce health inequities.

 

 

Roberta Berard, MD

 London Health Sciences Center 

 

 

 

Project Title: "Assessment of Juvenile Idiopathic Arthritis Outcomes and Place of Residence in Canada: Identifying Disparities in Care"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: Juvenile idiopathic arthritis (JIA) affects approximately 8000 Canadian children and it can lead to chronic pain and life-long disability. Attaining full control of pain and inflammation as soon as possible is essential to offer children with arthritis the best chance of a productive pain-free life. Where a family lives may be a barrier to accessing arthritis care and achieving timely control of a child’s joint pain and inflammation. In this study, we will use information volunteered by hundreds of Canadian children and parents from a national JIA Registry and information about home neighborhood characteristics from Statistics Canada. We will look at barriers to care related to geographic location and associated sociodemographic factors, and how this impacts timely control of pain and inflammation.

 

 

 

 Monica Aswani, DrPH

 University of Alabama at Birmingham

 

 

 

Project Title: "Representativeness of Participants in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: It can be difficult to conduct research in pediatric rheumatology due to low disease prevalence and rheumatologist workforce shortages. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry aims to address the challenges associated with pediatric rheumatology research by collecting longitudinal data from patients across multiple centers. However, examples of other disease registries suggest there can be systematic differences between patients who choose to enroll, compared to those who choose not to and those who are lost to follow-up. Therefore, our goal is to assess whether to what extent this may be the case in the CARRA Registry.


Large Grants

 

 

      

 Ashley Cooper, MD / Melissa Lerman, MD, PhD

 Children's Mercy Kansas City / Children's Hospital of Philadelphia

 

 

 

 

Project Title: "Adalimumab Levels in Induction Control for Chronic Anterior Uveitis"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: Pediatric uveitis is a serious disease that can cause permanent vision loss. Many children with noninfectious uveitis require treatment with tumor necrosis factor inhibitors (TNFi) to control uveitis and prevent complications. The most commonly used TNFi in childhood uveitis is adalimumab (ADA). Some children with uveitis respond to standard juvenile arthritis ADA dosing, while others require increased doses or do not achieve disease control on ADA. Therapeutic drug monitoring (TDM), a strategy of adjusting medication doses based on blood levels of the medication, is increasingly used in other diseases. TDM is not currently used in uveitis because target drug levels in uveitis are unknown. This project will enroll 85 children who are starting adalimumab for chronic anterior uveitis and measure ADA levels and antibodies several times in the first months of treatment. This pilot project is a first step towards defining optimal ADA trough levels in treatment of childhood uveitis.

 

 

 Daniel Horton, MD, MSCE

 Rutgers Robert Wood Johnson Medical School

 

 

 

 

 

Project Title: "Pilot of Adalimumab Withdrawal"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: Adalimumab (Humira) is the most used biologic used to treat juvenile idiopathic arthritis (JIA). Stopping adalimumab is a priority for many patients and families. We do not yet know how best to get patients off adalimumab or who can safely stop without flaring. While a randomized trial would help us learn how to stop adalimumab and who should or should not stop, we do not yet have enough information to start such a trial. For this reason, we propose the Pilot of Adalimumab Withdrawal (PAW). PAW will test 30 participants with JIA as they taper or stop adalimumab and 1-2 months later to see if they can collect blood samples at home. We will use small devices that collect blood from a fingerstick to see whether they are useful and acceptable to patients and families. This study represents a partnership among pediatric rheumatologists, laboratory scientists, and parent-scientists.

 

 

      

 Jessica Neely, MD / Jessica Turnier MD, MS

 UCSF​ / University of Michigan/C.S. Mott Children's Hospital

 

 

 

 

Project Title: "An Integrated Omics Approach to Characterize Biological Heterogeneity in Treatment Response and Target Therapy in Juvenile Dermatomyositis"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: Juvenile dermatomyositis (JDM) is a rare, childhood autoimmune disease that primarily affects muscle and skin, causing weakness and rashes. Many children with JDM do not respond fully to our initial therapies of steroids, methotrexate, and immune globulin, and for these patients, we do not always know the next best medicines. Likewise, we know that JDM occurs because of imbalances in our immune system. However, we do not know the
specific parts of the immune system that are affected. In this study, we will apply two technologies that measure the genes expressed and the proteins present in JDM patients who have a good response to therapy after 6 months of treatment and those who do not. By measuring the genes and proteins together, we will have a better understanding of how the immune system is working in JDM and how we can better target these imbalances with new medicines.


Small Grants

 

 

      

 Marinka Twilt, MD, MSCE, PhD / Dax Rumsey, MD, MSc, FRCP(C)

 Alberta Children's Hospital​ / University of Alberta

 

 

 

 

Project Title: "The Influence of the Condylar Disk on TMJ Arthritis Status and Treatment Response"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: Almost all children with childhood arthritis experience inflammation of the jaw during the course of their disease. To assess the jaw, detailed imaging (MRI) is needed. The jaw is a complex joint, consisting of different parts which together lead to a seamless opening and closing movement. One part is the disk, a structure that moves along the bone while opening and closing the mouth. If the disk is not in the correct position, the patient can feel or hear a click when opening or closing the mouth. It is unclear how often the disk is not in the correct position in patients with jaw arthritis and if this incorrect position leads to signs of inflammation on the MRI. In this study, we will use artificial
intelligence to determine the disk position on MRI and will try to relate these findings to treatment response.

 

 

 Melissa Oliver, MD

 Indiana University

 

 

 

 

Project Title: "Establishing a Core Domain Sets for Chronic Nonbacterial Osteomyelitis and Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis Syndrome"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: The CRMO/CNO workgroup aims to develop outcome measures to be used in all clinical trials with Chronic Nonbacterial Osteomyelitis (CNO) and Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) syndrome patients. The initial step is to develop a core domain set (CDS), which can be used for studying the success of treatments in persons with a certain disease. A domain is a specific aspect of health that should be measured or monitored. There are some outcome measures developed but they did not include the essential input from patients and families. In this project, we plan to run focus groups and online discussion boards with CNO/SAPHO patients and their parents/caregivers to get their input on important aspects of their disease. The goal of this project is to develop a list of important factors to must be considered when developing outcome measurements for patients with CNO, specifically from the perspective of patients and caregivers.


Advancing Biosample Collection Grants - PI

 

 

 Peter Nigrovic, MD

 Boston Children's Hospital

 

 

 

Project Title: "CARRA Samples for Funded LRA Global Team Science Award"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: Specific Aims: Project 2 of the GTSA award is termed: Define the genetic architecture of childhood-onset SLE. The Specific Aims of this project, illustrated in the Figure, are: Aim I. Define the burden of known rare and common risk variants in childhood-onset SLE. Through WGS, will establish the prevalence of risk variants in cSLE, with discovery-oriented sequencing of trios around children with outlier phenotypes lacking known causal variants. We predict that cSLE patients will exhibit a major burden of highly informative genetic risk variants. Aim II. Characterize heterogeneity in genetic footprints driving childhood-onset SLE. Categorizing risk variants by the pathways and cell subsets they affect, we will generate specific genetic risk scores (GRS) to identify genetic correlates for transcriptome-defined subgroups from Project I and secondarily other clinical and biological phenotypes. We predict that GRS will represent a stable correlate of biological phenotype in cSLE.

 

 

 Sampath Prahalad, MD, MSc

 Emory University

 

 

 

Project Title: "Genetic Ancestry Powered Studies in JIA"

Period Date: April 15, 2022 to April 14, 2024 

Lay Summary: Specific Aim 1a – We will expand existing JIA loci and identify new risk loci by performing a meta- analysis of existing datasets including genotypes from additional samples on hand (European and African Ancestry).
Specific Aim 1b - Using chromatin data in CD4+ T cells, existing genotyping sets, and new loci identified from our meta-analysis, we will identify candidate causal SNPs on the JIA-risk haplotypes that lie within non-coding regulatory regions.
Specific Aim 2: Having nominated candidate SNPs in functional regions, we will directly assess their effects on gene regulation in primary CD4+ T cells using massively parallel reporter assays (MPRA) [ 7 ]. We will further refine the list of candidates that emerge from MPRA screening by assessing their effects on DNA topology [ 8 ], an important regulator of genome function.
Specific Aim 3: Using both the genotyping data (Aim1a) and MPRA analysis, we will extend these findings to African Americans (AA) and will develop functionally based polygenic risk scores (PRS) that can be applied to both AA and European (EA) populations.