Axial spondyloarthritis (axSpA) is a chronic autoimmune disease of the spine and sacroiliac joints, characterized by persistent, inflammatory back pain.
While the prevalence of axSpA is noteworthy, impacting 1.4% of the adult population, which is more than double the rate of rheumatoid arthritis (RA) at 0.6%, it remains an under-recognized condition.
The current diagnostic pathway for axSpA is full of delays. Neil Klompas, CEO of Augurex, said the average diagnostic delay in North America is a staggering nine years. In contrast, a diagnosis for RA typically takes 11 to 22 months.
This disparity stems from the fact that chronic back pain, which affects nearly 28% of the US adult population, is not often considered an autoimmune issue by either patients or primary care physicians. Patients spend years rotating through non-disease-modifying treatments like physical therapy and chiropractic care, allowing the progressive disease to worsen and lead to permanent mobility issues.
Augurex, a patient-centric diagnostics company, is working to eliminate this diagnostic delay. Having pioneered JOINTstat, an in vitro diagnostic blood test for 14-3-3eta, a biomarker approved for diagnosing and monitoring RA, the company focused its efforts on axSpA for its second novel blood test, after identifying that its core biomarker innovation could significantly impact this area of high unmet medical need.
The Limitations of Traditional AxSpA Biomarkers
One of the central challenges in diagnosing axSpA is the lack of reliable, disease-specific biomarkers.
While autoimmune diseases are often grouped together, Klompas emphasized that each condition presents distinct diagnostic hurdles. Biomarkers commonly used in RA, such as antinuclear antibodies (ANA) and rheumatoid factor, are largely absent in axSpA, leaving clinicians with limited tools to differentiate inflammatory back pain from far more common mechanical causes.
Historically, clinicians have included C-reactive protein (CRP) and the genetic marker HLA-B27 in the diagnostic workup for axSpA, but neither provides sufficient diagnostic clarity on its own. CRP is a general inflammatory marker that can be elevated in many conditions and lacks disease specificity. HLA-B27 is strongly associated with axSpA, but the prevalence of the HLA-B27 gene varies significantly across populations — with lower frequencies observed in some African and East Asian groups compared with populations of European descent — limiting its diagnostic utility as a standalone marker.
The lack of specificity has left physicians without a reliable way to distinguish inflammatory autoimmune back pain from mechanical back pain, which accounts for the majority of chronic back pain cases seen in primary care.
Anti-14-3-3η: A Biomarker for Diagnostic Precision
Augurex’s approach builds on its earlier work in RA with the 14-3-3η protein. After validating its utility in RA, the company identified an opportunity to apply and expand this innovation in axSpA.
Through further assay development, Augurex developed a 14-3-3eta autoantibody multiplex immunoassay test called SPINEstat. Data presented at the American College of Rheumatology (ACR) annual meeting represented a significant milestone for the field.
Importantly, the findings demonstrated the potential to differentiate inflammatory back pain associated with axSpA from mechanical back pain, a distinction long considered a major unmet clinical need.
The data showed that anti-14-3-3η behaves similarly in mechanical back pain and healthy controls, while distinguishing patients with axSpA. In addition, SPINEstat was able to identify both radiographic axSpA, where structural damage is visible on imaging, and non-radiographic axSpA, an earlier disease stage that is frequently missed.
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FDA Breakthrough Device Designation and Its Implications
The significance of these findings was underscored by the FDA’s decision to grant Breakthrough Device Designation to Augurex’s axSpA diagnostic program.
For Klompas, the designation reflects both regulatory engagement and independent validation of the scientific approach.
“It also tells the clinicians and our investors and our business partners that the FDA has also independently looked at this,” he said.
Beyond external review, the designation signals recognition that axSpA represents an area of high unmet medical need, reinforcing the urgency of improving diagnostic pathways for patients who often wait years for an accurate diagnosis.
Designing Studies That Reflect Real-World axSpA
Accessing well-characterized axSpA cohorts remains a challenge, as the disease has historically been less studied than conditions such as RA or lupus.
Klompas noted that identifying the right investigators and longitudinal sample sets is essential for generating clinically meaningful data.
“The data that we presented at ACR recently came from two of the world’s best KOLs in this space,” he said, referencing collaborations with Walter P. Maksymowych, MD, PhD, at the University of Alberta, and Raj Sengupta at the University of Bath in the UK.
Building on this momentum, Augurex is expanding into additional cohorts to increase diversity across disease subtype, geography and ethnicity. This includes upcoming studies in Japanese populations, which are largely HLA-B27 negative.
The company is also prioritizing longitudinal studies to understand how anti-14-3-3η performs across disease duration, from early to later-stage axSpA.
Evaluating Diagnostic Performance and Clinical Relevance
For any diagnostic test to be used in routine care, clinicians need confidence that it performs consistently and accurately across patient populations. Klompas explained that this is why Augurex focuses on well-established performance measures that assess how effectively a biomarker distinguishes disease from non-disease.
These measures include receiver operating characteristic (ROC) curves, which summarize overall diagnostic accuracy, as well as specificity and sensitivity, which indicate how well the test correctly identifies patients with axSpA while minimizing false positives. Diagnostic odds ratios further help quantify how much a test result changes the likelihood that a patient truly has the disease.
A major step in demonstrating this level of performance is SPINEstat’s inclusion in the SPARTAN (Spondyloarthritis Research and Treatment Network) BASIS study, the largest prospective axSpA study in Canada. Participation in the BASIS study is expected to help inform future research approaches and clinical frameworks in axSpA.
From Diagnosis to Disease Monitoring
Klompas sees biomarker-based diagnostics as central to transforming autoimmune disease management across the full patient journey.
“I come from oncology where biomarkers are part of every step of the patient journey, from early screening with BRCA1 and BRCA2 to choice of therapeutics,” he said.
In rheumatoid arthritis, Augurex has shown that higher 14-3-3η levels are present in pre-RA and that patients with persistently elevated levels may remain at higher risk for radiographic joint damage, even when patient-reported signs and symptoms improve. Because 14-3-3η levels fluctuate with disease activity, the biomarker may also support monitoring strategies that allow clinicians to anticipate disease progression earlier.
“I’m excited as a scientist first that being able to rely on concrete measures from biomarkers to guide treatment decisions and to monitor patient progression and hopefully improvement is kind of what we’re all doing this for,” Klompas said.
Precision Diagnostics, Earlier Intervention and a Broader Impact
Looking ahead, Klompas believes earlier diagnosis will be critical to improving long-term outcomes in axSpA. He pointed to a key inflection point in disease progression.
“There’s kind of a breakpoint of five years where you start to see a permanent decrease in mobility in the spine,” he said. When diagnosis occurs after this window, structural damage may already be present.
Earlier diagnosis could also reduce reliance on symptom-based pain management approaches that often escalate as untreated inflammatory back pain becomes chronic. “We can do our part by identifying the chronic back pain patients that should be receiving anti-rheumatic agents and not pain meds,” Klompas said.
By enabling earlier and more accurate identification of inflammatory back pain, precision diagnostics have the potential to move care upstream, reduce long-term disease burden and improve quality of life for patients living with axSpA.
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