What are the manifestations of Ankylosing Spondylitis (AS)?

From the Guidelines

Ankylosing spondylitis (AS) primarily manifests as chronic inflammatory back pain, typically beginning in the sacroiliac joints and progressing up the spine, with symptoms and manifestations that can significantly impact morbidity, mortality, and quality of life 1. The disease is characterized by insidious low back pain and stiffness that worsens with rest and improves with activity, often causing morning stiffness lasting more than 30 minutes. As the disease advances, progressive fusion of the spine (bamboo spine) can occur, leading to decreased mobility and a characteristic stooped posture. Some key points to consider in the manifestations of AS include:

• Extra-articular manifestations such as anterior uveitis, which can cause eye pain, redness, and photophobia, affecting about 30% of patients 1
• Enthesitis, or inflammation at tendon insertions, commonly affecting the Achilles tendon and plantar fascia
• Peripheral arthritis, typically involving large joints like hips, knees, and shoulders in about 30% of cases
• Cardiovascular complications, including aortic regurgitation and conduction abnormalities
• Pulmonary involvement, leading to upper lobe fibrosis and decreased chest expansion
• Constitutional symptoms like fatigue, low-grade fever, and weight loss, often accompanying active disease
• A strong association with the HLA-B27 genetic marker, present in about 90% of patients, with the disease typically affecting young adults, particularly males, with onset usually between ages 15-45 1. Given the potential for significant morbidity and impact on quality of life, early recognition and management of AS are crucial to prevent long-term complications and improve patient outcomes 1.

From the FDA Drug Label

The safety and efficacy of HUMIRA 40 mg every other week was assessed in 315 adult patients in a randomized, 24 week double-blind, placebo-controlled study in patients with active ankylosing spondylitis (AS) who had an inadequate response to glucocorticoids, NSAIDs, analgesics, methotrexate or sulfasalazine Active AS was defined as patients who fulfilled at least two of the following three criteria: (1) a Bath AS disease activity index (BASDAI) score ≥4 cm, (2) a visual analog score (VAS) for total back pain ≥ 40 mm, and (3) morning stiffness ≥ 1 hour Improvement in measures of disease activity was first observed at Week 2 and maintained through 24 weeks At 12 weeks, the ASAS 20/50/70 responses were achieved by 58%, 38%, and 23%, respectively, of patients receiving HUMIRA, compared to 21%, 10%, and 5% respectively, of patients receiving placebo (p <0. 001) A greater proportion of patients treated with HUMIRA (22%) achieved a low level of disease activity at 24 weeks (defined as a value <20 [on a scale of 0 to 100 mm] in each of the four ASAS response parameters) compared to patients treated with placebo (6%)

The manifestations of ankylosing spondylitis include:

• Back pain: total back pain ≥ 40 mm on a visual analog score (VAS)
• Morning stiffness: ≥ 1 hour
• Bath AS disease activity index (BASDAI) score: ≥ 4 cm
• Bath Ankylosing Spondylitis Functional Index (BASFI): measures functional ability
• Inflammation: measured by the average of the last 2 questions on the 6-question Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
• Acute phase reactants: such as C-reactive protein (CRP)
• Spinal mobility: measured by Modified Schober's test
• Chest expansion
• Occiput-to-wall measurement

These manifestations are used to assess the severity of ankylosing spondylitis and response to treatment, such as adalimumab (HUMIRA) 2 or etanercept (Enbrel) 3.

From the Research

Ankylosing Spondylitis Manifestations

• Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that primarily affects the vertebral column and sacroiliac joints 4
• The disease process promotes extensive remodeling of the spinal axis via ligamentous ossification, vertebral joint fusion, osteoporosis, and kyphosis, resulting in a weakened vertebral column with increased susceptibility to fractures and spinal cord injury (SCI) 4
• AS is characterized by lower back pain, enthesitis, and asymmetrical peripheral arthritis 5
• The disease can cause severe, chronic pain, and in more advanced cases, it can cause spine fusion 6

Clinical Features

• Inflammatory symptoms, such as pain and stiffness, are common manifestations of AS 7
• Spinal cord injury is a complex problem associated with high morbidity and mortality rates in patients with AS, which can be attributed to the severity of the injury, associated medical comorbidities, and the advanced age of most patients with AS who suffer an SCI 4
• Patients with AS may experience enthesitis, which is inflammation of the sites where tendons or ligaments insert into the bone 5

Treatment-Related Manifestations

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are the first-line treatment in AS, but some patients are inadequately relieved of pain and inflammation by NSAIDs 7
• Biological therapies, such as tumor necrosis factor-alpha (TNF-alpha) blockers, have been shown to be highly efficacious in the treatment of AS, especially in patients with active and severe disease 8
• The use of NSAIDs and biological therapies can be associated with adverse events, such as gastrointestinal toxicity and serious infections, including tuberculosis 8, 5