SAA is a leader in Spondyloarthritis research. In addition to providing early career researcher grants, we sponsor a number of research projects that aim to find a cure and greater understanding of spondyloarthritis. Below is a sample of research projects funded by SAA.
This multi-site, cross-disciplinary (gastroenterology and rheumatology) study sought to understand the association between IBD (Crohn’s disease and ulcerative colitis) and spondyloarthritis (SpA). Many people with IBD experience joint pain and stiffness caused by SpA, which often goes undiagnosed. This research study aimed to improve the early detection of SpA in IBD patients using two screening questionnaires—DETAIL and IBIS-Q—and to identify any potential risk factors.
The researchers reported that nearly half of the participants exhibited symptoms of SpA. Despite this, most patients with SpA symptoms either did not have a formal diagnosis or had recently seen a rheumatologist. Risk factors associated with SpA symptoms included older age, female sex, smoking, severe IBD, and the use of biologic medications. The type of IBD (Crohn’s disease versus ulcerative colitis) was not associated with a higher likelihood of SpA symptoms.
These findings highlight the need for better SpA screening methods and improved referral pathways to specialists for timely diagnosis and treatment. Recognizing risk factors and utilizing effective tools such as DETAIL and IBIS-Q could help address the high rate of undiagnosed SpA in IBD patients.
Research team included: Michael H Weisman (Co-principal Investigator), Reem Jan (Co-principal Investigator), Simon J Hong, Rahul S Dalal, Kristine A Kuhn, Andrew Stahly, Frank I Scott, Benjamin Click, Anna Way, Fardina Malik, John M Davis III, Manar Shmais, Laura Raffals, Alexa Silfen, David T Rubin, Ishaan Dharia, Abhik Bhattacharya, Bahar Moghaddam, Trayton Mains, Jayde Kurland, Sheena Patel, and Joerg Ermann. Plain language summary by Joseph Stenberg.
SAA’s 2023 Spondyloarthritis Unmet Research Needs Conference IV convened at the National Institutes of Health (NIH) in Bethesda, Maryland to discuss the future of spondyloarthritis research and existing gaps of knowledge and understanding of the disease. The presenters were world renowned experts in the following specific areas that were identified by the planning committee to address unmet needs in SpA research: endotypes (disease subtypes), pain, imaging, disparities, and therapeutics.
In addition to inviting the leading spondyloarthritis researchers, a concerted effort was made to invite -and sponsor- researchers who are early in their careers to inspire and encourage them to be the next generation of leading scientists. These early career researchers were not only full participants in the conference, they also presented posters on their spondyloarthritis research. See below for the list of posters presented. Award winning posters are designated with a ⚑.
Not only does the conference provide strategic direction for the next 5-10 years of spondyloarthritis research, SAA remains committed to its fundraising efforts to continue to sponsor research that will lead to improved outcomes for people living with ankylosing spondylitis and related diseases. Demonstrating a major investment in research, 2023 is the latest link in a chain of SAA’s Unmet Needs Conferences held at NIH in 1998, 2006, and 2017.
Dr. Tejpal Gill and her research team at Oregon Health & Science University (OHSU) are studying metabolic profiles in the blood and feces of patients with axial spondyloarthritis (axSpA). They have successfully obtained samples from axSpA patients, including those with and without HLA-B27, and non-diseased individuals. The team hypothesizes that the microbial metabolites in the axSpA patients will be different from healthy controls, and these differences may help explain how the microbiome influences disease status and aid in developing new treatment options. They are currently collaborating with Dr. Ernesto Nakayasu at Pacific Northwest National Laboratory to analyze the samples using advanced technologies such as liquid chromatography-based mass spectrophotometry. Dr. Gill and her team continue to accept samples at OHSU but are looking to expand their collection across the United States. This plain language summary by Joseph Stenberg.
Dr. Kristi Kuhn and her research team are currently investigating how specific immune cells (i.e., T-cells) move around the body, specifically from the gut to other tissues, to help understand the connection between the gut and joints and their effect on spondyloarthritis. The team is looking at genetic expression patterns that may influence the migration behavior of the immune cells. While they succeeded in obtaining data from immune cells in the gut and spleen, they faced challenges with cells from joints. Early analysis of this data is promising, but more work needs to be done to interpret how these differences affect disease in spondyloarthritis. This plain language summary by Joseph Stenberg.
To help understand the cause of spondyloarthritis (SpA), this study investigated the microbiota of children at increased risk of developing SpA based on a family history of ankylosing spondylitis (AS) and HLA-B27 status.
Dr. Gensler’s research group analyzed the intestinal microbiota of the offspring of patients with AS. The offspring were further divided based on HLA-B27+/- status. F. prausnitzii was the key organism associated with HLA-B27+ status.
The research team also evaluated the microbiota in the offspring diagnosed with SpA and those without disease. The offspring in this category all had HLA-B27+ status. Notably, B. fragilis was associated with juvenile SpA patients, and F. prausnitzii had a higher abundance in those without SpA.
While F. prausnitzii was associated with HLA-B27+ status, it was depleted in juvenile SpA patients. This suggests that although HLA-B27 status can influence the microbiota, this alteration may not influence the development of SpA.
Research team included: Dr. Lianne S. Gensler (Principle Investigator), Dr. Matthew L. Stoll, Dr. Kimberly DeQuattro, Dr. Zhixiu Li, Dr. Henna Sawhney, Dr. Pamela F. Weiss, Dr. Peter A. Nigrovic, Dr. Tracey B. Wright, Dr. Kenneth Schikler, Dr. Barbara Edelheit, Dr. Casey D. Morrow, Dr. John D. Reveille, and Dr. Matthew A. Brown. Plain language summary by Joseph Stenberg.
This study used data from an online survey to access common concerns of Spondyloarthritis including ankylosing spondylitis and COVID-19.
Many patients are concerned with anti-inflammatory medication (e.g., anti-TNF, anti-IL-17, NSAIDs, sulfasalazine, etc.) and increased susceptibility to COVID-19 infection. Data collected from over 4300 patients revealed that anti-inflammatory medication did not increase the risk of COVID-19 infection.
Another concern was HLA-B27 status and increased susceptibility or severity of COVID-19 infection. Data collected from over 3400 patients showed neither an increased risk nor protective effect against COVID-19. The same data also revealed B27 status did not affect COVID-19 symptom severity.
This study also revealed that HLA-B27 status was negatively associated with axial spondyloarthritis (AxSpA) symptom severity. Plainly, AxSpA patients without HLA-B27 reported more severe disease than HLA-B27 positive patients. This reporting is opposite to the relation with HLA-B27 and ankylosing spondylitis (AS). Further, HLA-B27 is associated with lower disease activity in AxSpA and higher disease activity in AS.
Research team included: Dr. James T. Rosenbaum (Principle Investigator), Dr. John D. Reveille, Dr. Michael H. Weisman, Dr. Kevin L. Winthrop, Dr. Kimberly Ogle, Dongseok Choi, Hedley Hamilton of Any-3, Cassie Shafer, Elin Aslanyan, and Richard A. Howard. Plain language summary by Dr. Joseph Stenberg.
A major impediment to advancing the care of children with spondyloarthritis and axial arthritis is an absence of randomized clinical trials (RCTs) despite an increasing number of potential therapies. The lack of pediatric classification criteria for axial disease is a major impediment to the conduct of clinical trial research for juvenile spondyloarthritis (JSpA).
This project develops a classification criteria for axial JSpA that will enable identification of a more homogeneous group representative of children with SpA and axial disease for entry into observational or clinical trials. The deliverables for this project was to perform a multi-criteria decision exercise to determine the final criteria and relative weights of the axial disease criteria.
Investigator team: Weiss PF, Brandon TG, Aggarwal A, Burgos Vargas R, Colbert RA, Horneff G, Joos R, Laxer RM, Minden K, Ravelli A, Ruperto N, Smith J, Stoll ML, Tse SM, Van den Bosch F, Naden R. Principle Investigator Pamela Weiss MD MSCE
This study addresses why the microbiome is important in the development of spondylitis.
While microbiome studies identify differences in specific bacteria, a common bacterium has yet to emerge as a pathogenic factor in SpA. Focusing on the differences in how the microbiome as a whole functions, Dr. Kuhn’s research group has identified a link to the way dietary tryptophan is broken-down into inflammatory chemicals by the microbiome of individuals with SpA. Her group is evaluating how these inflammatory chemicals derived from tryptophan influence immune functions that lead to arthritis.
This study combines translational observations from a study population of people with AS with mechanistic wet-bench studies aiming to address the immunologic consequences of microbiome changes in patients with SpA. The study provides an important foundation to address why the microbiome is important in the development of SpA.
SpA represents a potential, silent cause of back pain among some who serve. Unfortunately, research on SpA among military service members has been minimal, and researchers found no data on the incidence of this disease or its risk factors in the US military prior to their study. This is a glaring information deficit in light of the impact of back problems on military disability. Gaining a better understanding of the rates and predictors of SpA and its associated functional outcomes in military populations could be important due to the exposures associated with military service.
Doctors Lianne Kurina, Michael Weisman, Alan Nelson, and Robert Kaplan found that in strong contrast to prior studies and conventional wisdom about a male predominance in SpA, researchers found that adjusted odds of SpA were very similar in men compared to women in this active, regularly-screened population with universal health care.
nr-axSpA is a type of spondyloarthritis that has the features of ankylosing spondylitis (AS) but does not have significant enough damage to the sacroiliac joint that is visible on plain x-rays to be easily classified as AS.
Delayed diagnosis of axial spondyloarthritis (axSpA) is well documented; little is known about the diagnostic journey and impediments for US people with non-radiographic axSpA (nr-axSpA). It is hypothesized that impediments are varied and exist at both the healthcare provider (HCP) and patient levels. This study sought to understand patient experiences and contributors to delayed nr-axSpA diagnosis in the US.In this mixed-methods study (qualitative and quantitative) of impediments to nr-axSpA diagnosis in the US, delayed diagnosis was common. Among surveyed patients, median time to diagnosis was 3.25 years, yet more than 20% had undiagnosed symptoms for over a decade. Diagnostic delay disproportionately affected women and patients living in rural areas. Barriers to timely diagnosis included patient tolerance for chronic pain, symptoms other than hallmark chronic low back pain prompting care, and episodic symptom flares seemingly related to strenuous activity. Furthermore, HCPs are typically unfamiliar with axSpA or hold outdated perceptions that contribute to delayed diagnostic testing and rheumatology referral, and qualified rheumatologists who understand axSpA are limited in number.
Research team consisted of: Atul Deodhar, MD (Principle Investigator), Richard Howard, MBA, Dongseok Choi, PhD, Sonam Kiwalkar, MD.
Dr. Rosenbaum’s research assessed the impact of ankylosing spondylitis (AS) on quality of life across physical, discomfort, social, and emotional domains. This study surveyed 716 patients suffering from AS in the United States. Research revealed that sex differences showed a greater impact of AS on quality of life in women versus men, with the most significant impact in the physical domain. This study identifies the impaired quality of life aspects for future improvements in AS treatment. Prior Life Impact Studies were conducted in 2002 & 2011. Plain language summary by Joseph Stenberg.
For two days in September of 2017, the Spondylitis Association of America brought together an international group of leading researchers to the National Institutes of Health (NIH) in Bethesda, Maryland, to identify pressing gaps, share insights, discuss scientific and treatment issues, and provide direction for the next decade of spondyloarthritis research. The Spondylitis Association of America and the National Institute of Arthritis, Musculoskeletal and Skin Diseases
(NIAMS) "Spondyloarthritis 2017: Unmet Needs Conference III" generated interdisciplinary collaborations among researchers and clinicians, and opened new areas of investigation to expand the breadth and depth of spondyloarthritis research. The 2017 gathering builds on SAA's inaugural Unmet Needs conference held in 1998, and Unmet Needs II in 2006. By physically bringing the top researchers in the country to network and discuss cutting edge research in other diseases, the conference laid the groundwork for the next several years of research and investigation into spondyloarthritis.
SAA Medical Board Member James Rosenbaum, MD, posed this question in SAA's news magazine, Spondylitis Plus. Since that article was published, SAA has assisted in funding his research to test his hypothesis.
The concept of inflammatory back pain (IBP) evolved in the 1970s, coincident with the discovery of the HLA-B27 association with ankylosing spondylitis (AS), leading to the development of criteria to determine the presence of IBP. The concept of IBP and it relationship with AS and axial spondyloarthritis (AxSpA) has further evolved, and an instrument developed (the Spondylitis Association of America Back Pain Tool), which was further modified and field tested for use in the 2009-2010 National Health and Nutrition Examination Survey (NHANES). This has shown the frequency of chronic back pain to have risen to 19.4%, with nearly one-third having IBP. The prevalence of AxSpA has been defined at 1.0-1.4% and AS at 0.52-0.55%. The national prevalence of HLA-B27 in the U.S. is 6.1%, and intriguing data from NHANES 2009 suggest a decreasing frequency with increasing age. From this arise new questions and a work agenda ahead.
Dr. Lianne Gensler is a rheumatologist at the University of California, San Francisco (UCSF) Medical Center and the Director of the Ankylosing Spondylitis Clinic. Dr. Gensler, Dr. Matt Stoll and Dr. Matt Brown were selected to receive funding for their MOSAS research study.
Multiple genetic and environmental factors result in the development of SpA diseases, including ankylosing spondylitis. In this study, Dr. Gensler et.al will evaluate children at increased risk of developing spondylitis based upon a family history of AS and positive HLA-B27 marker, comparing them to their HLA-B27 negative, and thus lower-risk siblings as well as to their disease-free parent. This will be the first study of its kind to evaluate the pre-disease microbiota in patients with a higher likelihood of developing arthritis.
Drs. Mark Asquith and James Rosenbaum’s research focuses on the potential role for fungus or yeast in the pathogenesis of spondyloarthritis. Microbiota is the community of micro-organisms that inhabit the interior and exterior of the human body at various tissue sites. Drs. Asquith and Rosenbaum’s research utilizes fungal microbiota to investigate a novel therapeutic strategy to reduce or prevent disease symptoms in AS patients.
From the American College of Rheumatology’s website, rheumatology.org:
The American College of Rheumatology (ACR) has released new recommendations for the treatment of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (SpA). The guideline was developed with the Spondylitis Association of America (SAA) and the Spondyloarthritis Research and Treatment Network. It summarizes recommendations for both pharmacologic and non-pharmacologic treatments, including rehabilitation, management of patients with comorbid conditions, use of certain surgeries, and approaches to patient monitoring.
SAA has seeded a national patient registry on ankylosing spondylitis. By combining three existing patient databases that have been used in research, the composite database can look at thousands and potentially tens of thousands of patients and be able to track health trends, disease severity over time, age, gender, race, and many other factors to improve understanding of the disease.
The Spondylitis Association of America has funded and helped create a state-of-the-art workshop for rheumatologists and radiologists called “Magnetic Imaging Workshop in Spondyloarthritis (SpA).” The purpose of this certified Continuing Medical Education program is to educate radiologists and rheumatologists in spondyloarthritis imaging and to promote earlier diagnosis in SpA.
SAA has helped fund the research of Joel Taurog, MD, into the association between HLA-B27 and ankylosing spondylitis. Dr. Taurog serves on SAA’s Medical and Scientific Advisory Board.
From Dr. Taurog’s profile on the University of Texas Southwestern Medical Center website, utsouthwestern.edu:
The goal of Dr. Taurog's research has been to understand the molecular basis for the association of the rheumatic disease called ankylosing spondylitis with the major histocompatibility allele HLA-B27. This MHC class I allele is found in 7 percent of the U.S. population, but in over 90 percent of individuals with ankylosing spondylitis. Of individuals with B27, it is estimated that up to 13 percent will develop ankylosing spondylitis or a related form of spondyloarthritis.
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