AS & nr-AxSpA

The term axial spondyloarthritis (axSpA) now is used frequently to describe patients with predominantly axial symptoms who fit into the spectrum of a well-recognised rheumatic disease that continues to be known as ankylosing spondylitis (AS). The 2009 Assessment of SpondyloArthritis international So…

The term ‘non-radiographic axial spondyloarthritis’ (nr-AxSpA) is much more important to classify than to diagnose patients with axial spondyloarthritis.

So, is nr-AxSpA the same animal as AS, but its “younger self”? Do all nr-AxSpA progress eventually to AS? Are treatments that work for AS and are approved for AS recommended for nr-AxSpA, or would these expensive biologics be an overkill if most nr-AxSpA do not progress to AS?

We need answers.

Axial spondyloarthritis may be a prolonged prodromal state, authors say

Depending on the duration of the study you are looking at, the percentage of nr-AxSpA progressing to AS varies, with longer studies generally yielding higher proportions.

Structural Progression in Axial SpA ‘Quite Small’

Fewer than 5% developed radiographic changes over 2 years

While the previous study yielded 26% of nr-AxSpA progressing to AS over 10 years, the figure understandably came in at <5% in this study of a mere 2-years’ duration.
It would be logical to say that some (not all, or even a majority) nr-AxSpA patients progress, and at different rates.
The next step is to determine what are the predictive factors for rapid structural progression, so as to treat these patients earlier and more aggressively (with biologics, perhaps) to forestall damage and disability.

Multiple Spine Symptoms Respond to Anti-TNF

Axial SpA, AS may be different phases of one disease
<p>Translating research into clinical practice. Arthritis Research & Therapy is a leading journal in the field of rheumatology and is notable for the breadth and quality of articles on the broad range of rheumatic and musculoskeletal diseases.…

It appears that nr-AxSpA has a female preponderance, and a consistently lower CRP (reflecting inflammatory burden) throughout the disease course. Response to treatment with anti-TNFs and compliance with therapy did not differ between the groups, with those with higher CRP (possibly more symptomatic and debilitating disease) responding better to and complying better with treatment.

So, it appears that nr-AxSpA represents a milder and earlier form of AS, and warrants treatment like AS, to be titrated according to the inflammatory burden (symptoms, CRP, MRI).

Determining the presence of radiographic sacroiliitis is a key feature in the diagnostic process of radiographic axial spondyloarthritis (r-axSpA), synonymous to ankylosing spondylitis according to the modified New York criteria (mNY).1 Its presence is considered prognostically relevant and paves the way for treatment with biological drugs.2 Multiread and multireader exercises have proven that radiographic sacroiliitis is an ambiguous finding, as reflected by large inter-reader and intrareader variability.3 ,4

Determining progression of radiographic sacroiliitis, which marks the arbitrary but irreversible change from non-radiographic axSpA (nr-axSpA) to r-axSpA, is even more ambiguous. The mNY lack sensitivity-to-change in this slowly progressing condition, and it is conceivable that regression of radiographic sacroiliitis is very rare if not impossible.5 Previous studies addressing progression from nr-axSpA to r-axSpA have ignored regression and have only interpreted progression.6 However, from a methodological perspective, bi-directional change cannot be ignored.

The aim of this study was therefore to assess positive and negative changes on plain pelvic radiographs (X-SI) over time in the Assessment of SpondyloArthritis international Society (ASAS) cohort, in which X-SI judgements have been provided by single local readers from many centres worldwide.

In the ASAS cohort, 975 patients with either chronic back pain (>3 months, onset <45 years) of unknown origin or undiagnosed peripheral symptoms were assessed at baseline.7 ,8 Of these, 564 patients were reassessed after a mean follow-up of 4.4 years (range: 1.9–6.8). Patients with paired X-SI available (at baseline and follow-up) were included and judgements of the local observer (rheumatologist/radiologist) at both time points (either by the same or other reader) were analysed. Positive cases were defined as definite radiographic sacroiliitis according to the mNY.

In total, 357 patients had paired X-SI available. Of these, 17.4% (62/357) fulfilled the criteria for r-axSpA (table 1). At follow-up, this proportion has raised to 22.4% (80/357) suggesting a net progression of 5%. Cross-tabulation, however, revealed that more than half (36/62) considered mNY-positive at baseline were assessed mNY-negative at follow-up (table 2). If true, this would mean that radiographic sacroiliitis would have regressed in 58% of the cases. Conversely, only 54/295 patients (18.3%) became positive at follow-up.

It is very difficult to interpret these data, since progression, regression and measurement error (leading to spurious change) cannot be disentangled. Under the untenable assumption of ‘no true change’, the kappa statistic would yield a very poor figure of 0.21 (only marginally better than chance-agreement), which would make it useless from a diagnostic perspective.

If only positive change (progression) is valued and negative change is ignored, one would disregard measurement error and spuriously attribute part of the observed positive change to real progression.

The most likely explanation of our strange and extreme observation is that subtle radiographic progression (the signal)—if truly present—cannot be reliably distinguished from measurement error (the noise). These sobering data clearly illustrate that more research is needed in visualising progression in axSpA. Imaging modalities other than radiographs should be evaluated in future such as MRI and low-dose CT.

It seems that progression on the nr-AxSpA to AS spectrum is not inexorably one-way: some “damage” visualised on XRays may potentially repair/improve😊 The authors urged caution as the small XRay changes either way may have been misread😔