The paradigm of non-radiographic sacroiliitis—why the ongoing doubts?

Abstract

The concept of non-radiographic axial spondyloarthritis (nraxSpA) gained prominence from the understanding that definite plain radiographic features of sacroiliitis evolve over many years, and diagnosis is often delayed, while treatment is particularly effective in the early stages of disease. Many patients presenting with features suggestive of SpA but without radiographic sacroiliitis were indiscriminately labeled as “undifferentiated SpA” but then denied highly effective tumor necrosis factor inhibitor (TNFi) therapies because the drug label confined treatment to those with radiographic sacroiliitis. It became necessary to capture these patients with early disease in new classification criteria that would include patients within a broader spectrum of axSpA, which became possible with the advent of MRI for early detection of sacroiliitis. This was accomplished using a two-pronged approach in the 2009 Assessments in SpondyloArthritis international Society (ASAS) classification criteria [1]: (1) An imaging arm allows patients to be classified as having axSpA if they have MRI evidence of sacroiliitis and at least one SpA feature. (2) A clinical arm permits classification of axSpA in the absence of MRI inflammation if the patient is positive for HLA B27 and has at least two SpA features. A positive MRI for the purposes of classification was defined by a 2009 consensus of ASAS experts as bone marrow edema (BME) on fat-suppressed scans or osteitis on T1-weighted contrast-enhanced scans in a typical subchondral location [2]. This definition required the presence of at least two BME lesions on a single semicoronal slice through the SIJ or a single lesion on two consecutive slices. The lesion also had to be considered “highly suggestive” of axSpA although what characteristics of the lesion would define it as “highly suggestive” were not elaborated. A 2016 consensus update of the 2009 ASAS definition further elaborated that the concomitant presence of structural lesions, especially erosion, could help determine whether the BME lesion was “highly suggestive” of axSpA [3]. Soon after publication of the criteria, several studies examined the characteristics of patients classified as nr-axSpA and demonstrated more females and a lower prevalence of HLAB27 as compared to studies that had classified patients using the modified New York criteria [4–6]. This led some to question the accuracy of the criteria, especially the clinical arm, by referencing studies which demonstrated that patients fulfilling only the clinical arm did not demonstrate progression to radiographic sacroiliitis and did not respond to TNFi in placebocontrolled randomized controlled trials (RCT) unless objective features of inflammation in the form of an elevated Creactive protein (CRP) or MRI inflammation were evident [6, 7]. Proponents of the criteria pointed to the observation that the clinical arm had similar predictive validity to the imaging arm for rheumatologist follow-up diagnosis of axSpA in the ASAS classification cohort [8]. In addition, patients fulfilling the “clinical arm” in the ASAS classification cohort actually had a mean of 3.4 SpA features and meta-analyses of international cohorts demonstrated similar sensitivity/specificity performance of the clinical and imaging arms for rheumatologist diagnosis of axSpA [9]. The authors of the review entitled “Understanding the Paradigm of Non-Radiographic Axial Spondyloarthritis (Benavent and Navarro-Compán)” [10] fall firmly into the camp of the proponents in arguing that the data supports the view that nr-axSpA resembles radiographic-axSpA (r-axSpA) in terms of the clinical manifestations, disease burden, and treatment response. Certainly, it is now undeniable that patient self-reported symptomatology and impact on quality of life are comparable between these two categories. In comparing patient characteristics and manifestations of disease, it is important to clarify that the diagnosis of axSpA is challenging in its early stages and disease manifestations may vary according to the duration of disease. Consequently, even though the * Walter P. Maksymowych [email protected]