What is the recommended treatment for bilateral chronic sacroiliitis with a negative HLA-B27 test?

Treatment of HLA-B27 Negative Bilateral Chronic Sacroiliitis

First-line treatment is NSAIDs at full dose, followed by physical therapy; if inadequate response after 2-4 weeks, advance to TNF inhibitors regardless of HLA-B27 status. 1, 2

Initial Pharmacological Management

• Start with the lowest effective dose of an NSAID as first-line therapy, with continuous evaluation and monitoring over 2-4 weeks 1
• If the first NSAID is ineffective after 2-4 weeks, switch to a different NSAID before escalating therapy 1
• HLA-B27 negative status should not delay appropriate treatment, as the disease can be equally severe as in HLA-B27 positive patients 2
• Strongly avoid systemic glucocorticoids for axial disease 1, 2

Physical Therapy (Essential Component)

• All patients should be referred to a subspecialist for a structured exercise program - this is a strong recommendation, not optional 1
• Active supervised exercise interventions are superior to passive modalities (massage, ultrasound, heat) 1
• Land-based physical therapy is preferred over aquatic therapy 1

Advancement to Biologic Therapy

When NSAIDs fail to control active disease:

• TNF inhibitors are the first biologic agent recommended, with strong evidence supporting their use 1, 2
• No particular TNF inhibitor is preferred over another 1
• Secukinumab or ixekizumab (IL-17 inhibitors) are strongly recommended alternatives if NSAIDs fail 1
• TNF inhibitors are conditionally preferred over IL-17 inhibitors as first biologic choice 1

Second-Line Biologic Options

If primary non-response to the first TNF inhibitor occurs:

• Switch to secukinumab or ixekizumab rather than trying a different TNF inhibitor 1, 2
• If secondary non-response (initial response then loss of efficacy) to TNF inhibitor, switch to a different TNF inhibitor over IL-17 inhibitors 1
• Tofacitinib is an option but TNF inhibitors and IL-17 inhibitors are preferred 1, 2

Medications to Avoid

• Do not add sulfasalazine or methotrexate to failed TNF inhibitor therapy; instead switch to a different biologic 1
• Sulfasalazine may be considered only for persistent peripheral arthritis, not for axial disease 2
• Never switch to a biosimilar of the same TNF inhibitor that failed 1

Local Glucocorticoid Injections

• For isolated active sacroiliitis despite NSAIDs, locally administered parenteral glucocorticoids may be considered 1, 2
• This is a conditional recommendation with very low quality evidence 1

Important Clinical Pitfalls

• Do not rule out axial spondyloarthritis based solely on negative HLA-B27 - approximately 10% of cases are HLA-B27 negative 1, 2
• Inflammatory markers (ESR/CRP) have limited sensitivity (≤50%) and normal values do not exclude disease 1, 2
• The diagnosis is often delayed 6-8 years, so maintain high clinical suspicion with inflammatory back pain characteristics (morning stiffness >30 minutes, nocturnal pain, improvement with exercise) 2, 3
• MRI of sacroiliac joints has 90% sensitivity and specificity for sacroiliitis, superior to plain radiography (80% sensitivity/specificity) 1

Monitoring Strategy

• MRI may help evaluate disease activity when uncertain, but systematic serial radiographic monitoring is not recommended 2
• Once stable on biologic therapy, do not routinely discontinue or taper the biologic dose 1, 2
• If receiving TNF inhibitor with NSAIDs or conventional DMARDs, consider continuing TNF inhibitor alone 1