BALTIMORE—Often in rheumatology, technical terms and definitions represent more than just semantics. Indeed, having a shared understanding among clinicians of what constitutes a clinical disorder or disease can be essential to appropriately diagnose and treat patients. At the 17th Annual Advances in the Diagnosis and Treatment of the Rheumatic Diseases meeting at the Johns Hopkins University School of Medicine, Baltimore, Atul Deodhar, MD, professor of medicine in the Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland, helped provide clarity on non-radiographic axial spondyloarthritis and other related topics.
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In 2009, Rudwaleit et al. published a landmark article describing the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis.1 Contrary to popular belief, the term non-radiographic axial spondyloarthritis (nr-axSpA) does not require the absence of sacroiliitis on imaging. Patients with definite radiographic sacroiliitis on X-rays (i.e., grade 2 bilateral or grade 3 or 4 unilateral sacroiliitis, according to the 1984 Modified New York Criteria for ankylosing spondylitis) and with at least one clinical feature of axial spondyloarthritis (axSpA) meet the definition for ankylosing spondylitis.
Meanwhile, patients can meet criteria for nr-axSpa in a number of ways: 1) having acute (active) inflammation of the sacroiliac joints on magnetic resonance imaging (MRI) with at least one clinical feature of spondyloarthritis; 2) having grade 2 unilateral or grade 1 unilateral or bilateral sacroiliitis on X-rays and meeting two or more clinical features of axial spondyloarthritis; or 3) demonstrating positive HLA-B*27 and meeting two or more clinical features of axial spondyloarthritis.1
Dr. Deodhar made several insightful points on this subject. First, he noted that the distinction between radiographic and non-radiographic axial spondyloarthritis is somewhat arbitrary. If one clinician believes that X-rays for a patient show only unilateral grade 2 sacroiliitis but another clinician believes they show bilateral grade 2 sacroiliitis, then the same patient would be labeled with nr-axSpA in the first instance and radiographic axial spondyloarthritis in the second instance. It’s impossible to say which clinician’s assessment is truly correct, and thus the labeling of the condition is in the eye of the beholder.
Nevertheless, Dr. Deodhar explained that identifying patients with nr-axSpA is an important starting point in following the course of disease. Fewer than 5% of patients with nr-axSpA have self-limiting disease: 5–30% of patients will progress from non-radiographic to radiographic axial spondyloarthritis over 2–30 years.2 This makes sense when one realizes that patients with advanced spondyloarthritis, including end-stage such features as bamboo spine, were not born with these imaging findings, but progressed from more mild to more severe radiographic changes over the course of their lives.
With respect to MRI, Dr. Deodhar pointed out that bone marrow edema at the sacroiliac joints can be seen in many healthy individuals and should not be used to diagnose spondyloarthritis without taking into account the entire clinical picture.
Weber et al. conducted a study in which MRI scans (T1‐weighted and short tau inversion recovery [STIR] sequences) of the sacroiliac joints were obtained from 187 subjects, including patients with non-specific back pain and healthy controls.3 Bone marrow edema, erosions and fat infiltration were observed in up to 27% of control subjects with non-specific back pain and in 24% of health controls.
Although it is possible that some of these patients may have clinically asymptomatic, atypical or early spondyloarthritis, the authors point out that the presence of low-grade, acute lesions of the sacroiliac joints may be due to mechanically induced signal alterations or degenerative changes, and, thus, care should be taken not to misclassify some young patients with back pain as having spondyloarthritis. The authors note that erosions were much less frequently observed in both control groups when compared with bone marrow edema and fat infiltration. Thus, erosive findings may be more specific for true spondyloarthritis.3
Dr. Deodhar also discussed the 2019 update of the ACR/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nr-axSpA.4 He noted that, in these guidelines, treatment recommendations for ankylosing spondylitis and nr-axSpA are similar.
Tumor necrosis factor (TNF) inhibitors remain recommended as the first-line biologic treatment for these patients and are recommended over interleukin-17 (IL-17) inhibitors, mostly because a more robust response is achieved using TNF inhibitor treatment and because TNF inhibitors treat many of the extra-articular manifestations of disease, such as uveitis. However, in patients who have had a primary nonresponse to TNF inhibitors, IL-17 inhibitors are recommended over trying a second TNF inhibitor.
TNF and IL-17 inhibitors are both recommended over using tofacitinib in patients with ankylosing spondylitis and nr-axSpA. Sulfasalazine was included in the guidelines as a treatment only for persistent peripheral arthritis and not for treatment of axial involvement.
Although routine monitoring of C-reactive protein is indicated for all patients, this is not the case for routine monitoring with MRI or radiographs of the spine or sacroiliac joints.
In addition, screening for osteoporosis with bone density scans is recommended for these patients.
Regarding items that are not advisable, the authors state that co-administration of low-dose methotrexate with a TNF inhibitor is not recommended. Discontinuation or tapering of biologics in patients with stable disease is also not recommended.4
On the subject of radiographic progression while on treatment, Dr. Deodhar noted that the traditional teaching has been that medications like TNF inhibitors do not prevent structural progression of disease. However, more recent studies have challenged this dogma. Dr. Deodhar noted that structural progression and inflammation are coupled in axial spondyloarthritis, and effective control of inflammation appears to reduce the rate of structural progression, at least as shown by retrospective observational cohort studies.
Prospective randomized clinical trials are the only gold standard method by which to confirm a cause-and-effect relationship between the use of biologics and inhibition of structural damage, and head-to-head clinical trials would be helpful in comparing the effects of different biologics against one another.
This lecture on ankylosing spondylitis and nr-axSpA was thought-provoking and clarified common misconceptions about these conditions.
Jason Liebowitz, MD, completed his fellowship in rheumatology at Johns Hopkins University, Baltimore, where he also earned his medical degree. He is currently in practice with Skylands Medical Group, N.J.
- Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (part II): Validation and final selection. Ann Rheum Dis. 2009 Jun;68(6):777–783.
- Garg N, van den Bosch F, Deodhar A. The concept of spondyloarthritis: Where are we now? Best Pract Res Clin Rheumatol. 2014 Oct;28(5):663–672.
- Weber U, Lambert RGW, Østergaard M, et al. The diagnostic utility of magnetic resonance imaging in spondyloarthritis: An international multicenter evaluation of one hundred eighty-seven subjects. Arthritis Rheum. 2010 Oct;62(10):3048–3058.
- Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019 Oct;71(10):1599–1613.