What are the treatment options for ankylosing spondylitis?

Treatment Options for Ankylosing Spondylitis

Start all patients with active ankylosing spondylitis on NSAIDs at maximum tolerated doses combined with regular physical therapy, and escalate to TNF inhibitors if disease activity remains high after an adequate NSAID trial. 1

First-Line Treatment: NSAIDs and Physical Therapy

NSAIDs as Primary Pharmacotherapy

• NSAIDs are strongly recommended as first-line drug treatment for all patients with AS presenting with pain and stiffness 1
• Approximately 75% of AS patients demonstrate good or very good response to full-dose NSAIDs within 48 hours, compared to only 15% of patients with mechanical back pain 1
• Continuous daily NSAID therapy is preferred over on-demand use for patients with persistently active symptomatic disease 1, 2
• Long-term continuous NSAID use may slow radiographic progression and reduce syndesmophyte formation, providing a potential disease-modifying effect beyond symptom control 2

NSAID Selection and Safety

• For patients with increased gastrointestinal risk, use either non-selective NSAIDs plus gastroprotective agents (PPIs or misoprostol) or COX-2 selective inhibitors 1
• Etoricoxib ranks as the most efficacious NSAID for AS based on network meta-analysis 3
• Monitor for gastrointestinal complications (serious GI events have RR 5.36 with traditional NSAIDs) and cardiovascular toxicity throughout treatment 1, 2

Physical Therapy

• Physical therapy and regular exercise are strongly recommended as fundamental components alongside pharmacotherapy 1, 4
• Individual and group physical therapy should be considered, with patient education programs 1

Second-Line Treatment: TNF Inhibitors

Indications for TNF Inhibitor Initiation

• TNF inhibitors are strongly recommended for patients with persistently high disease activity despite adequate NSAID treatment and physical therapy 1
• Define "adequate NSAID trial" as 3-6 months at maximum tolerated doses of at least two different NSAIDs before categorizing as NSAID-refractory 1
• No obligatory requirement to use conventional DMARDs before initiating TNF inhibitors in axial disease 1, 5

TNF Inhibitor Selection

• For patients with concomitant inflammatory bowel disease or recurrent iritis, use TNF inhibitor monoclonal antibodies (infliximab, adalimumab, certolizumab, golimumab) rather than etanercept 1, 4
• For patients without these comorbidities, no particular TNF inhibitor is preferred 1
• Available TNF inhibitors include adalimumab 40 mg every other week 6, etanercept 50 mg weekly 7, infliximab, certolizumab, and golimumab 1

TNF Inhibitor Efficacy

• Approximately 50% of NSAID-refractory AS patients achieve at least 50% improvement with TNF inhibitors 1
• In patients with disease duration <10 years, 72% achieve at least 50% improvement 1

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, 8
• These IL-17 inhibitors represent the preferred alternative biologic class after TNF inhibitor failure 1

Treatments NOT Recommended

Conventional DMARDs for Axial Disease

• Sulfasalazine, methotrexate, and leflunomide have no evidence of efficacy for axial manifestations of AS 1, 8
• Sulfasalazine may be considered only for patients with peripheral arthritis 1

Systemic Glucocorticoids

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

Surgical Interventions

• Total hip arthroplasty is strongly recommended for patients with advanced hip arthritis causing refractory pain or disability with radiographic structural damage, 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 1, 8
• Reassess at 4-6 week intervals when initiating or changing therapy 8
• HLA-B27 testing is useful for diagnosis but only needs to be performed once 5

Common Pitfalls to Avoid

• Do not discontinue NSAIDs prematurely—continuous use is preferred for active disease and may provide disease-modifying benefits 1, 2
• Do not use conventional DMARDs as a bridge to biologics in axial disease—they are ineffective and delay appropriate treatment 1, 5
• Do not rule out AS based on normal inflammatory markers alone—CRP and ESR can be normal even in active disease 5
• Do not switch from an effective originator TNF inhibitor to a biosimilar in stable patients—continue the current effective therapy 1