Is non-radiographic axial spondyloarthritis fact or fiction? In a lighthearted debate at ARA 2018 in Melbourne, two leading rheumatologists discussed the condition and whether it is a precursor to axial spondyloarthritis.
Queensland rheumatologist Associate Professor Peter Nash poses a challenge to a room full of rheumatologists on the first day of the Australian Rheumatology Association conference in Melbourne. He asks them if they recognise the clinical scenario of a patient who seems to have ankylosing spondylitis but without x-ray changes.
The patient is young, has severe chronic back pain and possibly synovitis, enthesitis, and dactylitis. Such patients are positive for the gene (HLA)-B27, have high CRP levels and other attributes of autoimmune inflammatory conditions – such as uveitis. But the traditional gold standard of diagnosis specified under the modified New York criteria – radiography – shows few or none of the abnormalities of ankylosing spondylitis, according to Associate Professor Nash, Director of the Rheumatology Research Unit on the Sunshine Coast.
This kind of patient, he says, is seen by many rheumatologists in Australia, and fits the category of non-radiographic axial spondyloarthritis (nrAxSpA). But there is uncertainty over the diagnosis and more importantly there is controversy over its potential for progression and how the condition should be managed.
Associate Professor Nash says the diagnosis of nrAxSpA is now recognised by eminent groups such as EULAR, and notes that a classification system and nomenclature for the condition was first developed by Assessment of SpondyloArthritis International Society (ASAS)1 in 2009 and has recently been updated. The ASAS criteria include MRI changes in the sacroiliac joints, but there is no objective biomarker for the condition. For Professor Nash there is no doubt that such patients have disabling inflammatory arthritis.
“We have a big group of undifferentiated patients who we thought had early disease and who we want to do something about treating their terrible symptoms,” he said.
But in Australia at least, the treatment options have been limited to physiotherapy and NSAIDs. The TGA has licensed the TNF inhibitors etanercept and the biologic golimumab for the treatment of nrAxSpA, but they are not listed on PBS because there is no agreement criteria that stipulates which patients may benefit from such agents.
Associate Professor Nash says a key question is whether these patients, as classified under ASAS criteria, have early disease that will progress to the more severe degenerative radiographic abnormalities of ankylosing spondylitis.
“Their x-rays haven’t changed yet, we have a window of opportunity,” he says.
To back this up, he points to a recent paper by Australian rheumatologists Dr Phil Robinson and Dr Matthew Brown2, who noted that in observational studies patients treated with TNF inhibitors showed retardation of radiological progression, and that MRI changes supported the link between inflammation and progression. And promisingly, withdrawal studies showed that there was a higher frequency of drug-free remission among patients who started treatment early.
However, according to Associate Professor Nash the key is to treat the individuals at high risk of progression, namely smokers, patients with high CRP levels and those with MRI abnormalities.
“Mounting evidence shows that early effective treatment of inflammation contains the outcome in the high risk individual. And if you stick to those predictors you are treating the right people,” he says.
Nevertheless, Associate Professor Nash challenges the ASAS assumption that nrAxSpA is a pre-radiographic form of AS in all patients.
Not all patients progress to radiographic changes and some patients show remission from their condition, he notes. In studies, the mean rate of progression has been 11.6% over two years3, with some studies showing 60% of patients progressing over ten years4.
This implies that early initiation of therapy will put many patients on treatment for many years prior to progression and others receiving treatment despite not facing progression – or perhaps even going into remission.
Associate Professor Nash argues this is where the expertise of the rheumatologist comes to the fore in using clinical judgement to select the patients with inflammatory signs and MRI changes for early biological therapy
“We should think about this not as pre-radiographic but as simply non-radiographic. It’s a heterogenous disease. Some patients will not progress and a group will even remit,” he says.
“But the symptoms and the burden of disease is very similar [to patients with ankylosing spondylitis]. These patients have real symptoms and they’re often incapacitated and we cannot ignore them.
“So we need the clinician armed with inflammatory markers and abnormal MRIs before the xray has a chance to change to decide the appropriate patient to treat more than NSAIDs and physio.”
Associate Professor Nash notes that professional groups such as ASAS and EULAR support the use of biological drugs in nrAxSpA, and the drugs have already been approved for reimbursement in Europe, but are still awaiting approval in Australia for PBS listing.
In a counter argument. Rheumatologist Professor Dennis McGonagle of the Leeds Institute of Rheumatic and Musculoskeletal Medicine, said the ASAS criteria to define nrAxSpA were too vague and could not be used to support the condition as a distinct entity.
Adopting a devil’s advocate position, he said a hockey player with mechanical rather than inflammatory damage to the spine could be diagnosed with nrAxSpA according to the ASAS criteria.
And with such loose criteria, the risk would be that many people without AS would be put on expensive biological drugs for many years.
“Non-radiographic axial spondyloarthritis confounds us. It’s very confusing, it’s a duck billed platypus,” he told the meeting.
According to Professor McGonagle, the doubts about ‘pre-radiographic’ disease had been supported by some studies that followed up patients, of whom many met the criteria for early inflammatory back pain. In one unpublished study only about 20% of patients showed a positive response to treatment.
He pointed out that if the ASAS criteria were extrapolated to the Australian population, assuming a 1.4% prevalence of nrAxSpA, this would mean there are 300,000 people with non-radiographic disease. Treating those under 45 years of age with biologics would cost $1.5 billion a year, he estimated.
“These are certainly patients who should be treated. I’m not against treatment. I’m just against the over zealous use of drugs,” he said
According to Professor McGonagle recent developments in biological science were steering us away from the concept of nrAxSpA and towards other ways of defining inflammatory back pain, as already seen with the genetic predisposition with the B27 gene.
“There isn’t a simple biomarker and I don’t think the ASAS non-radiographic criteria are relevant,” he said in his concluding remarks.
This article was sponsored by Janssen-Cilag Pty Ltd. The content is developed independently and is based on published studies and experts’ opinions. The views expressed are not necessarily those of Janssen.
- Rudwaleit M et al. The development of Assessment of Spondyloarthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection.
- Robinson PC et al. The window of opportunity: a relevant concept for axial spondyloarthritis. Arthritis Res Ther 2014;16(3):109.
- Poddubnyy D et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann Rheum Dis 2011; 70 (8): 1369-74.
- Mau W et al. Clinical features and prognosis of patients with possible ankylosing spondylitis. Results of a 10-year followup. J Rheumatol. 1988;15(7):1109–14