What are the associations of Ankylosing Spondylitis (AS)?

From the Guidelines

Ankylosing spondylitis is strongly associated with the HLA-B27 genetic marker, and its associations include inflammatory bowel diseases, uveitis, psoriasis, cardiovascular complications, osteoporosis, and pulmonary involvement, as part of the broader spectrum of spondyloarthropathies. The condition primarily affects the spine and sacroiliac joints but can also involve peripheral joints, eyes, intestines, and other organs. According to the 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations 1, AS affects 0.1–0.5% of the population, and is characterized by inflammatory back pain, radiographic sacroiliitis, excess spinal bone formation, and a high prevalence of HLA‑B27.

Some of the key associations of ankylosing spondylitis include:

• Inflammatory bowel diseases (particularly Crohn's disease and ulcerative colitis), with about 5-10% of ankylosing spondylitis patients having concurrent IBD
• Uveitis (anterior eye inflammation) occurs in about 30-40% of patients during their lifetime
• Psoriasis is another significant association, with approximately 10% of patients developing this skin condition
• Cardiovascular complications such as aortitis, aortic valve disease, and conduction abnormalities occur more frequently in these patients than in the general population
• Osteoporosis is also common, particularly in the spine, increasing fracture risk
• Pulmonary involvement may include upper lobe fibrosis and decreased chest wall expansion

These associations reflect the systemic nature of ankylosing spondylitis, which shares common inflammatory pathways mediated by TNF-alpha and IL-17, as noted in the 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations 1. This explains why treatments targeting these pathways (TNF inhibitors and IL-17 inhibitors) are effective for multiple associated conditions. The goal of treatment is to alleviate symptoms, improve functioning, maintain work ability, decrease disease complications, and forestall skeletal damage as much as possible 1.

From the FDA Drug Label

The safety and efficacy of Enbrel were assessed in a randomized, double-blind, placebo-controlled study in 277 patients with active AS. Patients were between 18 and 70 years of age and had AS as defined by the modified New York Criteria for Ankylosing Spondylitis Patients with complete ankylosis of the spine were excluded from study participation. The primary measure of efficacy was a 20% improvement in the Assessment in Ankylosing Spondylitis (ASAS) response criteria.

The associations of Ankylosing Spondylitis (AS) include:

• Active disease: defined by values of ≥ 30 on a 0-100 unit Visual Analog Scale (VAS) for the average of morning stiffness duration and intensity, and two of the following three other parameters:
  • Patient global assessment
  • Average of nocturnal and total back pain
  • The average score on the Bath Ankylosing Spondylitis Functional Index (BASFI)
• Modified New York Criteria for Ankylosing Spondylitis: used to define AS in patients
• Complete ankylosis of the spine: an exclusion criterion for study participation
• ASAS response criteria: used to measure efficacy, with a 20% improvement considered a positive response 2

From the Research

Associations of Ankylosing Spondylitis (AS)

The associations of Ankylosing Spondylitis (AS) can be categorized into several groups, including:

• Extra-articular manifestations
• Comorbidities
• Disease-related morbidities
• Treatment-related morbidities

Extra-Articular Manifestations

Extra-articular manifestations associated with AS include:

• Anterior uveitis (25-30%) 3, 4, 5
• Psoriasis (10-25%) 3
• Inflammatory bowel disease (5-10%) 3
• Cardiovascular manifestations 3
• Peripheral arthritis (approximately 30%) 3
• Enthesitis 3, 6

Comorbidities

Comorbidities associated with AS include:

• Osteoporosis 5
• Spinal fracture 5

Disease-Related Morbidities

Disease-related morbidities associated with AS include:

• Progressive, irreversible, structural damage to the axial or peripheral skeleton 7
• Inflammatory back pain 7, 5
• Enthesopathy 7

Treatment-Related Morbidities

Treatment-related morbidities associated with AS include:

• Toxicities from NSAID use 7
• Increased risk of infections and immunogenicity concerns with biologics 7