Ankylosing spondylitis diagnosis, treatment based on a ‘constellation of symptoms’
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Accurately diagnosing ankylosing spondylitis is a challenge for physicians, who must rely on a combination of symptoms and inflammation in place of a definitive blood marker.
Elevated levels of C-reactive protein can provide diagnostic value for ankylosing spondylitis, but Ana-Maria Orbai, MD, MHS, assistant professor of medicine at Johns Hopkins University, advises against using C-reactive protein as a primary indicator of the disease and instead making a wholistic assessment of a patient’s condition.
In this interview, Orbai discusses what to look for in diagnosis and treatment initiation and where research is headed to make this a more clear pathway for practitioners and patients.
How accurate are C-reactive protein (CRP) levels in predicting a response to TNF-blocker treatments in ankylosing spondylitis?
Generally, CRP decreases with biologic treatments. However, a decrease in CRP may not be linked to a clinical improvement in disease activity or slowing of damage progression.
The contribution of CRP to response will also depend on how treatment response is defined. Assessment of spondyloarthritis (ASAS) responses, for example, do not include CRP, whereas ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) responses do include CRP If there is disconnect between a patient’s CRP and their AS clinical disease activity results from the treatment study population may not extrapolate to the population in the clinic.
A common clinical situation is when CRP is not increased and the patient shows clinically active disease with inflammatory back pain and life impact symptoms (decreased physical activity, quality of life, increased fatigue, etc.). In such situations, CRP’s role in gauging disease activity is minimal and clinicians will need to rely more on the patient’s symptoms. However, symptoms may be non-specific and influenced by other issues, therefore the attribution to AS may be difficult to make. The ideal situation would be to have the symptoms, but also a biomarker which is directly measurable.
What do physicians need to know about disease biomarkers in ankylosing spondylitis?
Disease activity biomarkers would be extremely useful, however there are none that have been validated in axial spondyloarthritis (axSpA), and/or ankylosing spondylitis (AS).
There are several known genetic markers which help diagnosis and are associated with disease risk and are part of the disease classification criteria (HLA-B27).
Is there a more specific marker or diagnostic option that would better provide an idea of when patients should receive treatment?
In the absence of a disease activity biomarker, physicians will rely on symptoms and imaging. They may use a checklist of inflammatory back pain criteria, among which are: improvement of pain with exercise, improvement of pain with non-steroidal and anti-inflammatory drugs, increased pain in the morning, and symptoms developing before age 40.
If patients meet inflammatory back pain criteria, CRP is elevated and the patient is HLA-B27 positive, and there is imaging (radiographic or MRI) evidence of spondyloarthritis/sacroiliitis, there is no doubt about the diagnosis and treatment
However, if treatment was limited to a CRP threshold, very few patients would receive it because less than 50% have a CRP elevation, and physicians may miss patients with active disease. A CRP elevation is often associated with MRI changes. The MRI can be a useful tool to indicate active inflammatory spine or sacroiliac disease. Elements of active disease by MRI are synovitis, bone marrow edema, joint effusion, erosions of the SI joints.
More often, patients will meet only a few of these clinical criteria. And since an MRI is more likely to be positive if CRP is elevated – a significant proportion of patients will present with clinical symptoms alone.
In those situations, the decision to start a biological becomes difficult because that decision relies on a risk-benefit assessment. Physicians may find it difficult to rely on clinical symptoms alone and would prefer an unequivocal indicator that treatment is working to slow/reverse the pathological process.
Are there any new or promising identification methods on the horizon?
A recent article in Arthritis and Rheumatology described the presence of possible disease specific antibodies in axSpA that may aid in early identification of this disease. The three proteins they identified increase the specificity of diagnosis of axSpA from 71% of the current criteria to 91.5%.
Beyond diagnosis, response to treatment markers are needed as well, especially in people with normal CRP.
What about this research would be helpful to other physicians?
While it’s still far from being a clinical test because it needs to be validated, physicians should be looking for more markers. There should still be a research focus on finding a blood test to diagnose a disease, because being certain about a diagnosis is the first critical step. After that, trials need to be conducted in that patient population so that we can extrapolate the data to the correct group.
References
- Quaden, D. et al. Arthritis Rheumatol. 2020;doi: 10.1002/art.41427.
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