Initial Approach to HLA-B27 Negative Ankylosing Spondylitis

Diagnostic and Initial Evaluation

The American College of Rheumatology suggests that ankylosing spondylitis (AS) can occur in HLA-B27 negative patients, although it is less frequent (approximately 10% of cases) 1, 2
For patients presenting with chronic back pain (>3 months) with symptom onset before 45 years, characteristics of inflammatory back pain are essential for diagnosis, especially in the absence of HLA-B27 positivity 1, 3
Characteristics of inflammatory back pain include:
- Morning stiffness >30 minutes 1
- Nocturnal/early morning pain 1
- Improvement with exercise 3

The European League Against Rheumatism recommends that non-steroidal anti-inflammatory drugs (NSAIDs) at full dose constitute the first-line treatment, regardless of HLA-B27 status 4
For patients refractory to NSAIDs, sulfasalazine may be considered, particularly in cases of persistent peripheral arthritis 4

For patients with active disease despite NSAIDs:
- Tumor necrosis factor inhibitors (TNFi) are recommended as the first biologic agent to use 4
- Secukinumab or ixekizumab are recommended if the patient has primary non-response to the first TNFi 4
- Tofacitinib is an option, but TNFi, secukinumab, and ixekizumab are preferred 4

Magnetic resonance imaging (MRI) of the spine or pelvis may help evaluate disease activity when it is uncertain 4
Systematic radiographic monitoring with serial spine radiographs is not recommended 4
Inflammatory markers (ESR/CRP) have limited sensitivity (≤50%) and are not suitable as isolated screening parameters 1

HLA-B27 negative status should not delay appropriate treatment, as the disease can be just as severe as in HLA-B27 positive patients 1
Co-administration of low-dose methotrexate with TNFi is not recommended 4
A strict treat-to-target strategy or stopping/reducing biologics in patients with stable disease is not recommended 4

Patients with chronic back pain and inflammatory characteristics should be referred to a rheumatologist, even in the absence of HLA-B27 positivity 1, 3
The presence of sacroiliitis on imaging (radiography or MRI) also justifies referral to a specialist 3