Axial spondyloarthritis (axSpA) encompasses a group of chronic rheumatic conditions
characterised by inflammation in the axial skeleton. Ankylosing spondylitis (AS) is the
prototypic disease, requiring radiographic evidence of sacroiliitis in order to fulfil the
modified New York criteria. However, the requirement for radiographic evidence of
radiographic sacro-iliac damage in order to make a diagnosis of AS led to long delays
(average 10 years) from symptom onset to diagnosis. Furthermore, it was apparent that many
patients had symptoms and disability consistent with AS but never developed the required
degree of radiographic damage in order to fulfil these criteria. These issues became
particularly pressing with the development of effective therapy, initially in the form of TNF
(Tumour necrosis factor) inhibitors, for AS. In parallel, advances in magnetic resonance
imaging (MRI) enabled the detection of inflammatory changes of sacroiliac joints and the
spine prior to the development of structural radiographic damage on plain radiographs. As a
result, the Assessment of Spondyloarthritis international Society (ASAS) developed validated
classification criteria for axial Spondyloarthritis (axSpA). These criteria allowed a patient
chronic back pain to be classified with axSpA via imaging (x-ray or MRI) or clinical (but no
imaging) routes, without the requirement for plain film evidence of structural damage. While
these classification criteria were initially developed as classification criteria for use in
research studies, they have facilitated the earlier diagnosis and treatment of patients with
axSpA in clinical practice.
As a result, there have been major advances in AS and axSpA over the past decade. AxSpA has
essentially changed from a condition that was diagnosed late, once structural damage was
already present, with very limited treatment options to a condition that can now be diagnosed
increasingly early and treated with highly effective biologic agents for those with severe
disease. There have also been major advances in the understanding of the genetics and
pathophysiology of the condition, which has led to the development of new therapeutic agents
for SpA, which have already started reaching the clinic years. In combination, these changes
have transformed the lives of patients with axSpA.
However, significant unmet need and evidence gaps remain. Studies and audits indicate that
despite these advances, there are still delays in diagnosis. The reasons for the delays are
likely to be multifactorial but the impact of these delays on outcomes, particularly work and
functional, remain poorly defined. This is also compounded by the remaining uncertainty
around the natural history of axSpA in real-world settings - only a proportion of people with
non-radiographic axSpA (nr-axSpA) will ultimately develop progressive radiographic changes
and AS. While other work has started to identify those groups of patients at highest risk of
radiographic progression (including those who are HLA-B27 positive, male and/or smokers),
accumulating evidence suggests that effective therapy with biologic agents may delay this
progression, whilst the long-term impact of early diagnosis and therapy on other outcomes in
real-world settings remains unclear. Licensed biologic agents are effective in the management
of active axSpA, but remain expensive for health care funders. Thus, longitudinal data are
required to help justify their long-term use in real-world settings. Furthermore, despite
improvements in inflammation and musculoskeletal symptoms with biologic and
non-pharmacological therapies, many people with axSpA have ongoing issues with pain, fatigue,
functional and work impairment.
Much of the existing data also comes from clinical trials, which are poorly representative of
the general, wider population of people with axSpA. Similarly, clinical trials are usually
not of sufficient duration to address long-term impacts of the axSpA spectrum, including
extra articular manifestations (EAMs), comorbidities and multimorbidity.
Therefore, there is a requirement for longitudinal, real-world studies of inception cohorts
of people diagnosed with axSpA to maximise the benefits from the advances in axSpA, and to
address remaining areas of unmet need. This information can also help inform future
stratification and precision medicine strategies in axSpA.
