Axial spondyloarthritis (AxSpA) is a chronic inflammatory arthritis that primarily affects the axial skeleton, specifically the spine and the sacroiliac (SI) joints. Characterized by chronic back pain and stiffness, AxSpA often begins in early adulthood. The condition is classified into two types: non-radiographic axial spondyloarthritis (nr-axSpA) and Ankylosing Spondylitis (AS). Understanding this classification is important for managing the disease and determining appropriate treatment pathways. This article clarifies the relationship between these two terms and outlines the diagnostic and management approaches used by rheumatologists.
The Axial Spondyloarthritis Spectrum
Modern medicine views nr-axSpA and Ankylosing Spondylitis as points along a single disease continuum, not separate diseases. Both share the same underlying inflammatory mechanism: a misguided immune response causing inflammation in the joints and entheses (where tendons and ligaments attach to bone). Patients experience comparable symptoms, including chronic inflammatory back pain, stiffness, and fatigue, regardless of classification.
The shared pathology includes a genetic predisposition, most notably the presence of the HLA-B27 gene. Although highly associated with AxSpA, the gene’s presence does not guarantee the condition’s development. Because the inflammatory process is fundamentally the same in both forms, Axial Spondyloarthritis serves as the overarching category for these disorders.
Defining the Difference by Imaging Status
The classification of AxSpA depends primarily on the presence of visible structural damage to the sacroiliac (SI) joints on conventional X-ray images. Ankylosing Spondylitis (AS), also called radiographic axial spondyloarthritis, is diagnosed when definitive structural changes are visible on the X-ray. These changes typically include erosions, joint space narrowing, or the beginnings of fusion, assessed using standardized criteria like the modified New York Criteria.
Non-radiographic axial spondyloarthritis (nr-axSpA) is classified when patients have the clinical signs and symptoms of AxSpA, often with active inflammation, but their SI joint X-rays do not show clear, irreversible structural changes. Specialists recognize the arbitrary nature of this distinction because the disease process is continuous. A patient may experience severe symptoms and high disease burden for years before the damage progresses enough to cross the X-ray threshold. Therefore, the classification reflects a stage of structural progression rather than a difference in the underlying disease.
The Diagnostic Journey and Key Tests
Diagnosis begins with a clinical assessment focusing on the characteristics of the patient’s back pain. Inflammatory back pain typically starts insidiously before age 40, improves with exercise, and includes morning stiffness lasting over 30 minutes. A rheumatologist combines this clinical picture with specific tests to confirm the diagnosis and determine the classification.
Blood tests check for genetic risk factors, such as the Human Leukocyte Antigen B27 (HLA-B27). Although highly prevalent in AxSpA patients, the presence of HLA-B27 is supportive evidence but not sufficient for diagnosis alone. Inflammatory markers like C-reactive protein (CRP) are also measured, as elevated levels indicate active systemic inflammation and predict disease activity.
Magnetic Resonance Imaging (MRI) is essential for diagnosing nr-axSpA by detecting active inflammation in the SI joints. The MRI visualizes bone marrow edema (swelling and fluid accumulation), which indicates acute inflammation long before structural damage appears on an X-ray. For a patient with inflammatory back pain and a negative X-ray, evidence of bone marrow edema on an MRI often confirms the diagnosis of non-radiographic axial spondyloarthritis.
Shared Management Strategies
Since nr-axSpA and AS share the same underlying inflammatory pathology, their core management strategies are similar. The goal of treatment is to reduce inflammation, alleviate pain, and maintain spinal mobility and function. Treatment begins with non-pharmacological interventions, such as regular physical therapy and exercise, which are foundational for maintaining flexibility and posture.
Pharmacological treatment starts with Nonsteroidal Anti-inflammatory Drugs (NSAIDs), such as ibuprofen or naproxen, as first-line therapy. Continuous NSAID use is often favored over on-demand use for patients with active disease. If a patient does not respond adequately, the next step involves Biologic Disease-Modifying Antirheumatic Drugs (DMARDs).
These biologic therapies target specific immune system components that drive inflammation. Tumor Necrosis Factor (TNF) inhibitors are a well-established class used for both nr-axSpA and AS. Interleukin-17 (IL-17) inhibitors, such as secukinumab and ixekizumab, are also options for patients who do not respond to TNF inhibitors or have contraindications.
Understanding Disease Trajectory
A key question for patients with nr-axSpA is whether the condition will progress to Ankylosing Spondylitis (AS). Progression is possible, with studies showing that approximately 5% to 40% of nr-axSpA patients develop definitive radiographic changes of AS over two to 30 years. A significant portion of patients, however, will never develop the X-ray changes required for reclassification.
Several factors are associated with a higher likelihood of progression:
- Male sex.
- Elevated C-reactive protein levels.
- Presence of active inflammation (bone marrow edema) on baseline MRI.
- Being HLA-B27 positive, which often leads to more severe radiographic damage over time.
The uncertainty of progression emphasizes the importance of early diagnosis and consistent management. Clinicians aim to suppress the disease activity that leads to structural damage by controlling inflammation through effective treatment, including NSAIDs and biologics. Early intervention offers the best chance of slowing or preventing radiographic progression, helping patients maintain function and reduce long-term disability.