What is the timeline of disease progression in Axial Spondyloarthritis (AxSpA)?

Timeline of Disease Progression in Axial Spondyloarthritis

Axial spondyloarthritis progresses over years to decades, beginning with sacroiliac joint inflammation, potentially advancing to spinal involvement and ankylosis, with structural changes evolving slowly over the course of years and requiring at least 2 years between imaging assessments to detect progression. 1

Diagnostic Delay Phase

• The mean delay from symptom onset to diagnosis is 4.9 years, though estimates in the USA suggest delays up to 14 years, representing a critical window where disease activity remains uncontrolled 1, 2
• This diagnostic delay occurs despite inflammatory back pain being present in 70-80% of patients, highlighting the challenge of early recognition 3
• Only 37% of patients in the USA are diagnosed by rheumatologists, with the majority diagnosed in primary care, chiropractic, or other non-rheumatology settings, contributing to delayed recognition 2

Initial Disease Phase: Sacroiliac Joint Involvement

• Disease classically begins with sacroiliac joint inflammation, presenting as lower back and buttock pain with alternating buttock pain being characteristic 1, 3
• Patients with ankylosing spondylitis typically develop bilateral sacroiliitis, while other subtypes (such as psoriatic spondyloarthritis) may develop unilateral or bilateral involvement 1
• Inflammatory changes on MRI may be present before radiographic changes become apparent, defining the nonradiographic axSpA phase 1

Progression to Spinal Involvement

• After initial sacroiliac joint involvement, disease may progress to involve the spine, though the pattern can be variable with a minority having isolated spine involvement 1
• The thoracic spine and thoracolumbar junction are the most common sites of spinal involvement when disease advances 1
• This progression occurs over years, not months, with structural changes evolving slowly 1

Radiographic Progression Timeline

• Radiographic changes evolve slowly over the course of years, requiring at least 2 years between imaging assessments to detect meaningful structural progression 1
• A portion of patients with nonradiographic axSpA will progress to radiographic axSpA (ankylosing spondylitis) over the course of years, though not all patients follow this trajectory 1
• The inflammatory changes of enthesitis, synovitis, and osteitis result in bone erosion, sclerosis, bone formation, and potentially ankylosis at sites of involvement over time 1

Disease Activity Trajectories

Disease activity does not follow a uniform pattern across all patients. Research from the DESIR cohort identified five distinct trajectories over 3 years of follow-up 4:

• Persistent moderate disease activity (36.2% of patients) 4
• Persistent inactive disease (17.8% of patients) 4
• Changing from very high to inactive disease (7.8% of patients) 4
• Persistent high disease activity (34.1% of patients) 4
• Persistent very high disease activity (4.1% of patients) 4

More than 30% of patients remain in trajectories with persistent high disease activity, and these patients face significantly increased risk of work disability (hazard ratio 5.2-8.0) 4

Advanced Disease Phase: Ankylosis

• Patients who develop advanced disease with ankylosis face spinal rigidity combined with osteoporosis, creating risk of fracture even with low-energy trauma or no apparent trauma 1
• These fractures are often unstable, involve all three spinal columns, and most frequently affect the cervical spine 1
• Neurologic deficits occur in 21-100% of patients with these fractures, with other complications in 84% of patients 1
• Diagnosis of these fractures can be delayed in 15-41% of cases, and outcomes carry relatively high morbidity and mortality 1

Peripheral and Extra-Articular Manifestations

• Approximately 30-50% of patients develop associated peripheral arthritis or enthesitis at some point during their disease course 1, 3
• Extra-articular manifestations including uveitis, psoriasis, and inflammatory bowel disease may occur at any point in the disease timeline 3

Impact on Functional Status

• Worsening functional impairment over time correlates with worsened structural changes and disease activity in ankylosing spondylitis specifically 1
• High levels of disease activity are associated with more profound decreases in quality of life measures 1
• Paraspinal muscle atrophy may develop and is associated with disease progression, structural damage, and functional limitations, being more prevalent in advanced stages 5

Critical Clinical Pitfall

The slow evolution of structural changes should not delay treatment initiation. While radiographic progression requires years to detect, inflammatory disease activity causes ongoing damage and functional impairment from the outset. Early treatment with biologics (TNF inhibitors) has been shown to slow progression of structural damage and may help prevent or minimize complications like muscle atrophy 1, 5