Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton including the spine and the sacroiliac joints. The hallmarks of axSpA are inflammation and new bone formation at the axial skeleton and entheseal sites (where tendons insert into the bone). Inflammation takes place, accompanied by bone and cartilage loss with subsequent remodeling with new bone formation. Despite the advancements in drug development for axSpA in recent years, there is still unmet needs for a timely diagnosis and higher rates of response to treatment (with 40% of patients currently not responding to available therapies).
ECM remodelling occurring in the affected tissues, can be quantified by tissue-specific biomarkers. This enables the monitoring of disease activity, providing valuable insights into the disease mechanisms and complexity in axSpA. Mesuring ECM biomarkers levels in patients with axSpA may assist in early diagnosis, disease management, and the identification of novel therapeutic targets.
Tissue remodeling and immune cell activity play pivotal roles in axSpA. Assessing disease activity and remodeling in axSpA can provide a unique insight into structural and functional changes in the disease pathogenesis. In addition, one of the key features of the biomarkers is the ability to monitor the disease activity, pharmacodynamic effects, and identification of disease endotypes.
Our rheumatology biomarker panels offer extracellular matrix-based-based biomarkers, which are fundamentally more different and more specific compared to what’s offered by omics providers. Our technology provides valuable insights into tissue formation, degradation, and resolution, that offer a deeper understanding of pathological processes related to joint diseases. At the same time, proteomics providers' wide-range arrays may not offer the same level of mechanistic specificity.
The delicate equilibrium between repair and response within the ECM becomes disrupted by the infiltration of immune cells into the inflamed tissue. This disruption results in excessive production and activation of proteases such as matrix metalloproteinases (MMPs). Type I collagen is found in cartilage and bone. The biomarker C1M, which measures type I collagen degradation by MMPs, can differentiate between patients with axSpA and other subjects with the same back conditions or healthy controls (Figure 1). This same biomarker also serves as a pharmacodynamic biomarker, being suppressed after 6 or 12 weeks of treatment with Adalimumab (a TNF-α inhibitor) compared to placebo in two clinical trials, DANISH and ASIM (Figure 2).
Figure 1. The C1M biomarker can differentiate between patients with axSpA from other subjects suffering from other back/pelvic pain conditions (women with postpartum pain, patients with disc herniation) and healthy controls (cleaning staff, long-distance runners, healthy men). |
Figure 2. The C1M biomarker is suppressed after 6 or 12 weeks by axSpA patients benefiting from Adalimumab (TNF-α inhibitor) compared to patients receiving placebo in two clinical trials (DANISH and ASIM). |
Like other chronic inflammatory diseases, the natural course of axSpA is highly heterogeneous. There exists a spectrum of inflammation, concomitant extra-articular manifestations, and varying degrees of structural damage within patients with axSpA. Improved patient stratification or the identification of disease endotypes, rather than disease phenotypes, may thus enhance drug response rates and lead to a more precise disease taxonomy. By using ECM biomarkers, three endotypes were identified: high levels of tissue inflammation markers, low levels of tissue inflammation markers, and high levels of cartilage turnover markers (Figure 3). |
Figure 3. Principal component analysis biplot of individuals and principal component dimensions. Ellipses represent 80% of the patients within the cluster, which are differentiated by colour. Cluster 1, 2 and 3 correspond to Endotype1, 2 and 3, respectively. |
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints. It falls under the broader category of spondyloarthritis, which includes conditions like ankylosing spondylitis. AxSpA typically manifests as back pain and stiffness that worsen with rest and improve with activity. Onset usually occurs in young adulthood, with symptoms persisting over time and potentially leading to spinal fusion in severe cases.
The exact cause of axSpA is not fully understood, but it is believed to involve a combination of genetic predisposition and environmental factors. The hallmark feature is inflammation of the axial skeleton, which can be visualized through imaging techniques like X-rays and MRI scans. Treatment aims to alleviate symptoms, reduce inflammation, and prevent structural damage. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as first-line therapy, with biologic medications reserved for those who do not respond adequately to NSAIDs.
Axial spondyloarthritis can significantly impact quality of life due to chronic pain, reduced mobility, and potential spinal deformities. Early diagnosis and appropriate management are essential for minimizing disease progression and improving long-term outcomes. Patient education, physical therapy, and regular monitoring are key components of a comprehensive treatment approach for axSpA.
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