What is the management approach for patients with HLA (Human Leukocyte Antigen) B27 negative ankylosing spondylitis?

Management of HLA-B27 Negative Ankylosing Spondylitis

The management approach for HLA-B27 negative ankylosing spondylitis is identical to HLA-B27 positive disease, with the same treatment algorithm prioritizing NSAIDs as first-line therapy, followed by biologics for refractory cases, combined with mandatory patient education and regular exercise throughout the disease course. 1

Core Management Principles

The treatment strategy does not differ based on HLA-B27 status because skeletal manifestations, disease severity, functional impairment, and radiographic progression are essentially the same in both HLA-B27 positive and negative patients. 2 The primary goal remains maximizing long-term health-related quality of life through control of symptoms and inflammation, prevention of structural damage, and preservation of function and social participation. 1

Treatment Must Be Individualized Based On:

• Current disease manifestations (axial, peripheral, entheseal, extra-articular symptoms) 1
• Level of current symptoms, clinical findings, and prognostic indicators 1
• General clinical status including age, comorbidities, and concomitant medications 1

Non-Pharmacological Treatment (Foundation of Care)

Patient education and regular exercise form the cornerstone of non-pharmacological treatment and must be implemented from diagnosis onward. 1

• Supervised exercise programs (land or water-based, individual or group) are more effective than home exercises alone and should be preferred 1
• Physical therapy improves patient global assessment significantly even when pain and function metrics show modest changes 1
• Patient associations and self-help groups provide additional support 1

First-Line Pharmacological Treatment

NSAIDs (including COX-2 inhibitors) are recommended as first-line drug treatment for patients with pain and stiffness. 1

• Continuous NSAID treatment is preferred over on-demand use for patients with persistently active, symptomatic disease 1
• NSAIDs provide convincing evidence (Level Ib) for improving spinal pain, peripheral joint pain, and function 1
• Cardiovascular, gastrointestinal, and renal risks must be assessed before prescribing 1
• For patients with increased GI risk, use non-selective NSAIDs plus gastroprotective agents or selective COX-2 inhibitors 1

Second-Line Options for Inadequate NSAID Response

Analgesics (paracetamol and opioid-like drugs) may be considered for residual pain after NSAIDs have failed, are contraindicated, or poorly tolerated. 1

Corticosteroid injections directed to local sites of musculoskeletal inflammation may be considered, but systemic glucocorticoids for axial disease are not supported by evidence. 1

Biologic Therapy for Refractory Disease

Anti-TNF treatment should be given to patients with persistently high disease activity despite conventional treatments. 1

Recent evidence demonstrates that multiple biologic classes are effective in HLA-B27 negative patients:

• TNF inhibitors remain highly effective 1
• IL-17 inhibitors (including bimekizumab, a dual IL-17A and IL-17F inhibitor) significantly improve disease activity, physical function, pain, quality of life, and spinal mobility in both radiographic and non-radiographic axial spondyloarthritis 1
• JAK inhibitors have demonstrated efficacy and good tolerability 1
• There is no evidence requiring obligatory use of DMARDs before or concomitant with anti-TNF treatment for axial disease 1

Important Distinction for Peripheral Disease:

• Sulfasalazine may be considered for patients with peripheral arthritis, but there is no evidence for efficacy in axial disease 1
• Methotrexate similarly lacks evidence for axial manifestations 1

Management of Extra-Articular Manifestations

One critical difference in HLA-B27 negative patients: acute anterior uveitis is significantly less common compared to HLA-B27 positive patients. 2 This suggests uveitis may be an independent HLA-B27-associated condition rather than a direct AS manifestation.

• Psoriasis, inflammatory bowel disease, and other extra-articular manifestations should be managed in collaboration with respective specialists 1
• Rheumatologists must remain aware of increased cardiovascular disease and osteoporosis risk 1

Monitoring Strategy

Regular monitoring should include:

• Patient history and clinical parameters 1
• Laboratory tests (inflammatory markers) 1
• Imaging according to clinical presentation 1
• ASAS core set assessments 1
• Frequency determined individually based on symptoms, severity, and drug treatment 1

Critical Pitfalls to Avoid

Do not assume HLA-B27 negative AS is a milder disease or different entity—clinical features, functional class, degree of deformity, pain severity, X-ray changes, and frequency of peripheral joint involvement are identical between HLA-B27 positive and negative patients. 2

Do not delay appropriate treatment while pursuing additional genetic testing—approximately 10% of AS cases are HLA-B27 negative, and alternative genetic markers like HLA-B13 and HLA-B37 may contribute through similar pathogenic mechanisms. 3, 4

Do not use DMARDs as a mandatory step before biologics for axial disease—this delays effective treatment without evidence of benefit. 1

Surgical Considerations

Total hip arthroplasty should be considered in patients with refractory pain or disability and radiographic evidence of structural damage, independent of age or HLA-B27 status. 1 Spinal corrective osteotomy and stabilization procedures may be valuable in selected patients. 1