What are the treatment options for ankylosing spondylitis?

Treatment Options for Ankylosing Spondylitis

NSAIDs are the first-line pharmacological treatment for ankylosing spondylitis with pain and stiffness, and should be used continuously at maximum tolerated doses in patients with persistently active disease, followed by TNF inhibitors for those with inadequate response. 1

First-Line Treatment Approach

Non-Pharmacological Management

• Physical therapy and regular exercise are strongly recommended as foundational elements of treatment and must be combined with pharmacological therapy. 1
• Individual and group physical therapy should be incorporated into the treatment plan. 1
• Patient education programs are essential components of comprehensive management. 1

NSAIDs as Primary Pharmacological Treatment

• NSAIDs are strongly recommended as first-line drug treatment for all patients with AS experiencing pain and stiffness. 1
• Approximately 75% of AS patients show good or very good response to full-dose NSAIDs within 48 hours, compared to only 15% of patients with mechanical back pain. 1
• Continuous NSAID therapy is preferred over on-demand use in patients with persistently active, symptomatic disease. 1
• For patients with increased gastrointestinal risk, use either non-selective NSAIDs plus gastroprotective agents (PPIs reduce serious GI events by 60%, RR 0.40) or selective COX-2 inhibitors (which reduce serious GI events by 82% compared to non-selective NSAIDs, RR 0.18). 1

Common Pitfall: Do not discontinue NSAIDs prematurely—ensure adequate dosing and duration (at least 6 weeks at maximum tolerated dose) before declaring treatment failure. 2

Second-Line Treatment: TNF Inhibitors

When to Initiate TNF Inhibitors

• TNF inhibitors are strongly recommended for patients with persistently high disease activity despite adequate NSAID treatment and physical therapy. 1
• The definition of "adequate NSAID trial" requires testing NSAIDs at maximum tolerated doses for sufficient duration before categorizing as refractory. 1

TNF Inhibitor Selection

• No particular TNF inhibitor is preferred for most patients—adalimumab, etanercept, infliximab, certolizumab, and golimumab are all appropriate options. 1
• Exception: For patients with concomitant inflammatory bowel disease or recurrent iritis, TNF inhibitor monoclonal antibodies (adalimumab, infliximab, certolizumab, golimumab) should be used instead of etanercept. 1
• Approximately 72% of patients with disease duration <10 years achieve at least 50% improvement with TNF inhibitors. 1

FDA-Approved TNF Inhibitors

• Adalimumab (Humira): 40 mg subcutaneously every other week for AS. 3
• Etanercept (Enbrel): 50 mg subcutaneously weekly for AS. 4
• Both agents can be used alone or with methotrexate, glucocorticoids, NSAIDs, or analgesics. 3, 4

Third-Line Treatment: IL-17 Inhibitors

• Secukinumab or ixekizumab are recommended for patients who are primary non-responders to TNF inhibitors or have contraindications to TNF inhibitors. 1
• These IL-17 inhibitors represent the next step after TNF inhibitor failure. 1

Treatments NOT Recommended

Conventional Synthetic DMARDs

• There is no evidence for efficacy of DMARDs (including sulfasalazine and methotrexate) for axial disease. 1
• Sulfasalazine may be considered only in patients with peripheral arthritis, not for axial manifestations. 1
• There is no requirement to use DMARDs before initiating TNF inhibitors in axial disease. 1

Systemic Glucocorticoids

• Systemic glucocorticoids are strongly recommended AGAINST for axial disease. 1
• Local corticosteroid injections directed to specific sites of musculoskeletal inflammation may be considered for peripheral manifestations. 1

Adjunctive Analgesic Therapy

• Simple analgesics (paracetamol) and opioids may be considered for pain control when NSAIDs are insufficient, contraindicated, or poorly tolerated. 1
• These should be used as adjuncts, not replacements for anti-inflammatory therapy. 1

Surgical Interventions

• Total hip arthroplasty is strongly recommended for patients with refractory pain or disability and radiographic evidence of advanced hip arthritis, independent of age. 1
• Spinal corrective osteotomy and stabilization procedures may be valuable in selected patients with severe deformities. 1

Disease Monitoring Strategy

• Monitor disease activity using patient history, clinical parameters (including ASAS core set), laboratory tests (ESR, CRP), and imaging according to clinical presentation. 1
• Frequency of monitoring should be determined by symptoms, severity, and current drug treatment—reassess at 4-6 week intervals when initiating or changing therapy. 5
• Important caveat: Normal CRP and ESR do not rule out active disease, as these markers can be normal even with ongoing inflammation. 6

Safety Monitoring for Biologic Therapy

Pre-Treatment Screening

• Test all patients for latent tuberculosis before initiating TNF inhibitors and periodically during therapy. 3, 4
• Complete age-appropriate vaccinations prior to starting biologic therapy. 4

Ongoing Surveillance

• Monitor closely for signs and symptoms of serious infections during and after TNF inhibitor treatment, including possible TB reactivation even in patients who tested negative initially. 3, 4
• Be aware of increased risk for invasive fungal infections (histoplasmosis, coccidioidomycosis) and opportunistic infections (Legionella, Listeria). 3, 4
• Discontinue TNF inhibitor immediately if serious infection or sepsis develops. 4

Critical Warning: Lymphoma and other malignancies, including rare hepatosplenic T-cell lymphoma, have been reported with TNF blockers, particularly in adolescent and young adult males receiving concomitant azathioprine or 6-mercaptopurine. 3, 4