We recently gave approximately $160,000 toward childhood arthritis research in the form of research grants. The grants are funded through the Childhood Arthritis and Rheumatology Research Alliance (CARRA); small grants were given to pediatric rheumatologists and fellows small grant research awards were given to third year fellowship students.
Osteoarthritis Center of Excellence Research Story
Over the last month, we’ve kept you updated on the work being done by the researchers in our osteoarthritis (OA) center of excellence (OA COE). The COE is currently funding three Clinical Trial Network demonstration studies that may lead to better diagnosis and earlier treatments for arthritis. Researchers from six different institutions will collaborate in various aspects of these cutting-edge studies. This is the last in a series of three blogs describing these studies.
Most people with partial or complete rupture of the anterior cruciate ligament (ACL) develop post traumatic OA (PTOA) within 10 to 20 years after their injury. Unfortunately, current ACL injury treatment options (both surgical and non-surgical) are successful in the short-term but do little or nothing to reduce the risk of developing PTOA later.
All three of the current OA COE are demonstration projects that build on knowledge gained from earlier foundation-funded ACL and PTOA research.
- Xiaojuan Li and her team of investigators are working to refine and standardize biomarker assessment in cartilage images obtained through magnetic resonance imaging (MRI) to allow earlier diagnosis.
- Virginia Byers Kraus and her team are working to identify which biomarkers are most critical for predicting risk of OA after injury and to confirm the earliest and best timepoints to start treatments.
- Christian Lattermann and his research team are working on establishing a clinical trials platform to put it all together in a demonstration project allowing for the exploration of new therapeutic strategies to prevent PTOA. This platform is designed to incorporate and further validate findings with regards to early biochemical biomarkers and (MRI) imaging biomarkers and patient reported outcomes (PROs) for pain and function.
Dr. Lattermann and his team are basing their OA COE project on what they learned from an earlier Arthritis Foundation-funded study. In 2012, Dr. Lattermann received an Innovative Research Grant for his 2-year project, “IL-1RA Treatment in Patients with Acute ACL Tear and Painful Effusions,” which he worked on with Dr. Kraus. Due to unforeseen difficulties, this study was modified to use a corticosteroid (an anti-inflammatory agent) instead of a blocker of IL-1. The study was the first of its kind to evaluate the effect of an early anti-inflammatory intervention and biomarker profiles in the first couple of weeks after ACL injury. In brief, this study concluded that PTOA begins at the time of ACL injury. In this early study, 49 young adult patients were treated with corticosteroid or placebo at 4 days and 2 weeks following the ACL injury. The study showed that while early treatment with corticosteroid did reduce collagen breakdown in cartilage, it didn’t reduce the anti-inflammatory biomarkers (Interleukin-1 or IL-1) in patients.
Following the previous study, the team continued to work on the FDA approval to use an iL-1 blocker that we believe to be even more effective in blocking inflammation than cortisone. The current OA COE study is now looking at how this injectable drug (also known as IL‑1 receptor antagonist or IL-1Ra) may reduce the risk of developing PTOA in adolescents and young adults (aged 14 to 33) with ACL tears. The goal is that the drug will reduce the level of IL-1 in patients, thereby reducing the future risk of developing PTOA. IL-1Ra is currently used to treat rheumatoid arthritis, juvenile inflammatory arthritis, and post-surgical knee swelling. Dr. Lattermann and his team have received permission by the FDA to treat and study patients after ACL injury using IL-Ra.
Patients who take part in this study will be placed by random into one of three treatment groups:
- Group 1 will receive a placebo injection at Visit 1(about 4 days after injury) and an IL-1Ra injection at Visit 2 (about 2 weeks after injury).
- Group 2 will receive an IL-1Ra injection at Visit 1and a placebo injection at Visit 2.
- Group 3 will receive placebo injections at Visits 1 and 2.
Dr. Lattermann and his team will look at the changes in biomarkers in synovial fluid, blood, and urine at different times beginning within 7 days of the injury for up to 1 year. Knee imaging in the form of MRI scans and x-rays will also be performed for up to 2 years to look for changes.
By looking at biomarkers and knee imaging, researchers hope to pinpoint not only if the drug treatment may be effective, but also the best time to begin treatment to prevent further damage. About 60 patients are planned to be enrolled in this study, with the first patient starting in April.
Dr. Lattermann, the principal investigator, will coordinate the analyses with researchers at the University of California San Francisco and Duke University. Dr. Lattermann is currently a Professor for Orthopaedics and Sports Medicine at the UK College of Medicine (Department of Orthopaedic Surgery and Sports Medicine).
Osteoarthritis Center of Excellence Research Story
Our osteoarthritis (OA) center of excellence (COE) is currently funding three Clinical Trial Network demonstration studies that may lead to better diagnosis and earlier treatments for OA. Researchers from six different institutions will collaborate in various aspects of these cutting-edge studies. The three studies are connected to one another for a common purpose and they build on previous research funded by the Arthritis Foundation. This is the second in a series of three blogs describing these studies. Read the first one here.
Dr. Virginia Byers Kraus is working to identify biochemical biomarkers found in synovial (joint) fluid and urine from post-traumatic OA patients who have suffered anterior cruciate ligament (ACL) rupture. The samples used for this study come from samples collected from a 2013 Arthritis Foundation-funded project that validated using magnetic resonance imaging (MRI) techniques to measure the molecular changes that begin to occur in joints immediately after an ACL tear.
Urine and synovial fluid (from damaged knee joints) were collected from patients at five timepoints: baseline (less than 4 weeks after the joint injury), during surgery (about 6 weeks after the injury), 6 weeks after surgery, 6 months after surgery, and 1 year after surgery. The analysis of the 177 urine samples and 101 synovial fluid samples will take about 6 months.
The goal of this project is to evaluate which biochemical markers are connected to inflammation and cartilage breakdown following ACL rupture. The team is working to identify which biomarkers are most critical for predicting risk of OA after injury and to confirm the earliest and best timepoints to start treatments.
“With heart attacks, we treat immediately for best results,” explained Dr. Kraus. “We’re hoping to show that the same is true for joint injuries. What is important is the time from the injury to medical intervention. We must treat early to prevent further damage. What we currently see is that about half of the patients who have surgery for an ACL tear eventually develop more serious disease.”
By identifying biomarkers that appear early following an injury and by using more sensitive MRI imaging techniques, researchers hope to identify the individuals at highest risk for more serious joint disease and to determine the “window of opportunity” for providing treatment to prevent subsequent OA. Earlier interventions might include new drugs designed to halt the disease process and other anti-inflammatory drugs, thus reducing the need for joint replacements later and improving the quality of life.
Dr. Kraus was inspired to study OA by her father. Her father, a surgeon during the Vietnam War, damaged his hip and as a result endured 3 hip replacements over the rest of his life. While her father continued working into his 70’s, Dr. Kraus felt frustrated watching his daily suffering and the suffering of her clinic patients. It’s pushed her to want to make a difference and stop OA in its tracks.
“Osteoarthritis is a big and challenging beast -it’s the most prevalent disease in the world,” she explained. “It affects mobility, which in turn affects your heart and many other aspects of your health. We’ve begun to see success in understanding many types of arthritis, but up to now, we haven’t been as successful with OA. It’s so frustrating for me to see the suffering caused by this disease.”
We’re so proud to call Dr. Kraus a Champion of Yes. She explained why she likes to submit her research projects to us: “The Arthritis Foundation has stayed the course in maintaining prolonged interest in finding a cure. It has worked at building on prior innovative research – it’s hard to get funding for these types of studies. The Foundation has created a nimble mechanism for doing this type of research and moving it forward faster. This brings us closer to finding cures for patients more quickly.”
Dr. Kraus, the principal investigator in this project, is a professor of Medicine, Pathology and Orthopaedic Surgery at Duke University in Durham, NC. She will be working with other researchers from Duke University, as well as researchers from the University of California San Francisco (UCSF), Hospital for Special Surgery (HSS) in NYC, and the Mayo Clinic in Rochester, MN.
Osteoarthritis (OA) affects over 30 million people and is the most common cause of disability in adults in the U.S. The Arthritis Foundation has set the goal of advancing OA treatments as one of its highest priorities, making it one of the Foundation’s four scientific initiatives. To do this, we have created the OA Center of Excellence (COE), where researchers from around the county can join the Clinical Trial Network to work together to accelerate the development of new OA therapies.
The OA COE is currently funding three Clinical Trial Network demonstration studies that may lead to better diagnosis and earlier treatments. Researchers from six different institutions will collaborate in various aspects of these cutting-edge studies. We will look at each of these studies in a series of blogs.
New research predicts that the existing shortage of rheumatologists will worsen over the next decade, while the demand for arthritis specialists will continue to grow.
“In 10 years, we will have a significant challenge in America to take care of the demands of rheumatology care. Every region in the U.S. will be negatively affected by [having] far less rheumatologists than we think will be optimal,” says Daniel F. Battafarano, DO, division director, Rheumatology Service, San Antonio Military Medical Center in Texas.
Enhancing Communication Between Patients and Health Care Teams
Pilot Network to Launch Soon
The Arthritis Foundation is currently supporting the development and rollout of four specific scientific initiatives. These breakthrough initiatives are shaping the way new arthritis treatments are developed and will strengthen the relationship between you, your health care team. One of these initiatives is dubbed “Collaborating With Patients for Better Health” and the central component to this project is the Rheumatology Learning Health System.
What is the Rheumatology Learning Health System (RLHS)? The RLHS is a process that builds better bridges of communication between doctors and their patients to improve health outcomes by providing a wholistic picture of a patient’s condition – from not only clinic visit data, but also data entered by patients in between clinic visits and complemented by available research data. It is the central piece of our Collaborating with Patients for Better Health science initiative. The RLHS will be enabled by a shared electronic platform that will provide the means for this patient-provider produced health record. The complexity of the project requires that it be tested at a small number of sites to ensure that it works as planned. It will allow for new ideas and concepts to be “incubated” and tested thoroughly before growing the RLHS.
This proof of concept pilot network project will test the RLHS at six sites – three pediatric and three adult sites. So far, three pediatric sites have been selected for this project: Hackensack Meridian Health in New Jersey, Stanford Health Care in California, and Wake Forest Baptist Health -Brenner Children’s Hospital in North Carolina. The adult patient sites will be selected soon. The pilot project will span two years (from February 2018 to February 2020).
The RLHS will securely house information from 3 different sources that will be available to participants through patient and health care provider coproduced dashboards:
- Electronic patient health records maintained at individual medical practices: This contains information obtained during a medical visit, prescription information, and any patient test results ordered by a doctor
- Information entered by patients themselves between visits with their doctors: These are known as patient reported outcomes, and includes information about general health, how a patient is feeling, how many joints are inflamed or painful, or side effects from medications
- Existing arthritis patient registries: Databases of patient health information typically used for research
RLHS design features will include patient and health care provider decision support and shared decision-making tools, as well as features to support patient self-management.
The RLHS is being created through collaboration between the Arthritis Foundation, the Childhood Arthritis and Rheumatology Research Alliance (CARRA), the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN), Understanding Childhood Arthritis Network – Canadian/Dutch Collaboration (UCAN, CAN-DU), and the Dartmouth Institute for Health Policy & Clinical Practice. Each participating organization has contributed to the co-design of this system and guides its path forward.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) recently announced award recipients for the CARRA-Arthritis Foundation 2018 large and small grant awards. Grants are awarded to investigators with projects that positively impact the pediatric rheumatology scientific community. Funded by the Arthritis Foundation, a total of almost $240,000 was awarded for this year’s grants. Alpha Omicron Pi Foundation (AOII), a funding partner, funded three of the grants noted below.
“These grants are important because of the rarity of these patients, “explained Guy Eakin, PhD, senior vice president of Scientific Strategy. “Research on rare conditions is difficult, and required broad networks like the partnership between the Arthritis Foundation and CARRA to launch great ideas, then turn them into active research programs. We’re very proud to work in partnership with CARRA to see these and other major scientific initiatives moving forward.”
Of the 9 grants awarded, 5 are related to systemic lupus erythematosus (SLE) studies, 3 are related to juvenile idiopathic arthritis (JIA) studies, and 1 looks at tracking localized disease with mobile apps.
LARGE GRANT AWARDEES
Two applications were selected to receive $50,000 awards:
- Kiana Johnson, East Tennessee State University: Healthcare Transition Readiness and Health Self-management among youth with Juvenile Systemic Lupus (funded by AOII)
- Kathleen O’Neil, Indiana University School of Medicine: The Relationship Between Changes in Adipokine Levels and Disease Activity in Pubertal Children with SLE
Seven new small grants of up to $25k each were awarded. Congratulations to:
- Fatima Barbar-Smiley, Nationwide Children’s Hospital: Immunogenicity of pneumococcal vaccination and impact on nasopharyngeal pneumococcus colonization in patients with childhood onset systemic lupus erythematosus
- Ingrid Goh, The Hospital for Sick Children: Patient and Caregiver Engagement in Research (PACER): Approaching for research on date of rheumatic diagnosis—a pilot project (funded by AOII)
- Joyce Hui-Yuen, Cohen Children’s Medical Center: Feasibility of Conducting Epigenetic Analysis in Pediatric Lupus B Cells
- Suzanne Li, Hackensack University Medical Center: Tracking Disease Activity in Juvenile Localized Scleroderma with a Mobile App (funded by AOII)
- Melissa Oliver, Indiana University, Riley Hospital for Children: Clinical disease manifestations associated with anti-TNF non-response in Juvenile Spondyloarthropathy
- Victoria Werth, The University of Pennsylvania: Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in pediatrics
- Leandra Woolnough, Texas Scottish Rite Hospital for Children: Longitudinal Musculoskeletal Ultrasound Assessment in Juvenile Idiopathic Arthritis
CARRA will continue with the large grants program in 2019. The deadline for the next round of large grants will be March 1, 2019. Visit the CARRA website for details on other funding opportunities.
Lupus is a chronic, autoimmune disease and affects a wide part of the body, including the joints, kidneys, skin, blood, brain and other organs. One of our six Delivering on Discovery projects focuses on Lupus and lung disease. “Lupus is a complex disease. It affects many organs. The number of lupus patients with lung inflammation is probably underestimated. Yet it negatively impacts the quality of life in these patients,” explained Dr. Caroline Jefferies. “And while we have a basic understanding about how lupus affects various organs, we need to better understand how it affects the lungs to better manage and treat it.”
Dr. Jefferies is focusing on the lungs with her 3-year Arthritis Foundation-funded project, “Inflammatory neutrophils in lupus lung disease – novel cellular target”.
Why is my immune system attacking my joints? What is the cause? If you have rheumatoid arthritis (RA), this is something you have probably wondered at some point. It’s something Dr. Edward Doherty has wondered as well, and is currently studying. Dr. Doherty and his co-investigator, Dr. Pathricia Tilstam are studying key cells that drive inflammation in their 2-year Arthritis Foundation-funded project, “MIF/CD74 signaling as a new candidate for immunotherapy of rheumatoid arthritis”. With autoimmune disorders like RA, something triggers the immune system to malfunction and attack healthy cells, causing inflammation and disease. Dr. Doherty and Dr. Tilstam are looking for some of the triggers to help develop more effective treatments to stop progression and joint destruction.
Our patients have spoken: “We want earlier diagnoses to stop disease progression and better biomarkers for earlier diagnosis”
On March 8th, 2017, the Arthritis Foundation, US Food and Drug Administration (FDA), osteoarthritis (OA) patients, drug developers, health care providers and academic researchers came together to discuss the serious burden of OA disease, particularly the most significant OA-related symptoms, the impact of those symptoms, currently available treatments and ideal treatments.