What are the treatment options for ankylosing spondylitis?

Treatment Options for Ankylosing Spondylitis

Start with NSAIDs as first-line therapy for all patients with pain and stiffness, and escalate to TNF inhibitors if disease activity remains high despite adequate NSAID trials. 1

Initial Treatment Approach

Non-Pharmacological Foundation

• Patient education and regular exercise must be initiated immediately upon diagnosis as these are cornerstone treatments that improve long-term outcomes 1, 2
• Physical therapy should be incorporated, with group therapy showing superior patient global assessment outcomes compared to individual therapy alone 2
• Individual and group physical therapy sessions should be considered based on patient preference and availability 1

First-Line Pharmacological Treatment: NSAIDs

NSAIDs are the recommended first-line drug treatment with Level Ib evidence demonstrating improvement in spinal pain, peripheral joint pain, and function over 6-week periods 1, 2

NSAID Selection Strategy:

• For patients with standard gastrointestinal risk: Use any NSAID at maximum tolerated dose 1
• For patients with increased GI risk: Use either non-selective NSAIDs plus gastroprotective agent (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
• Continuous NSAID treatment is preferred over on-demand use for patients with persistently active, symptomatic disease, as continuous therapy may prevent new bone formation 1

Important NSAID Considerations:

• Trial at least two different NSAIDs at maximum tolerated dose for at least 3 months each before declaring NSAID failure 2
• Cardiovascular, gastrointestinal, and renal risks must be assessed before prescribing 1
• NSAIDs carry significant GI toxicity (RR 5.36 for serious GI events) and modest cardiovascular effects (RR 0.86) 1

Second-Line Options for Inadequate NSAID Response

Analgesics (paracetamol and opioids) may be added for pain control when NSAIDs are insufficient, contraindicated, or poorly tolerated 1, 3

Advanced Therapy: TNF Inhibitors

Anti-TNF treatment should be initiated in patients with persistently high disease activity (BASDAI >4) despite conventional treatments including at least two NSAIDs for at least 3 months 1, 2

TNF Inhibitor Selection:

• No particular TNF inhibitor is preferred for axial disease alone 1, 3
• For patients with concomitant inflammatory bowel disease: TNF monoclonal antibodies (infliximab, adalimumab, certolizumab, golimumab) are strongly preferred over etanercept 1, 3
• For patients with recurrent iritis: TNF monoclonal antibodies should be used 1

TNF Inhibitor Dosing (FDA-Approved):

• Adalimumab (Humira): 40 mg subcutaneously every other week 4
• Etanercept (Enbrel): 50 mg subcutaneously weekly 5

Duration and Monitoring of TNF Inhibitor Therapy:

• Long-term treatment is recommended; discontinuation is not advised as 60-74% of patients relapse after stopping 3
• Discontinuation might only be considered in patients with sustained remission for several years, with understanding that two-thirds will relapse 3
• Dose tapering is not recommended as a standard approach 3
• Regular monitoring of disease activity using validated measures (BASDAI, ASAS core set) is recommended 3

Switching Biologics:

• For primary non-response to first TNF inhibitor: Switch to secukinumab or ixekizumab over switching to a different TNF inhibitor 3
• For secondary non-response: Switch to a different TNF inhibitor over switching to a non-TNF biologic 3

Treatments with Limited or No Role

DMARDs for Axial Disease:

There is no evidence for efficacy of DMARDs (sulfasalazine, methotrexate) for axial disease 1

• Sulfasalazine may be considered only for patients with peripheral arthritis 1, 6
• DMARDs are not required before or during anti-TNF treatment for axial disease 1, 4
• Co-treatment with low-dose methotrexate is not recommended for patients on TNF inhibitors 3

Corticosteroids:

• Systemic corticosteroids for axial disease are not supported by evidence and should be avoided 1, 2
• Corticosteroid injections directed to local sites of musculoskeletal inflammation (peripheral joints, entheses) may be considered 1, 2

Surgical Interventions

Total hip arthroplasty should be considered in patients with refractory pain or disability and radiographic evidence of structural damage, independent of age 1

Spinal surgery (corrective osteotomy, stabilization procedures) may be valuable in selected patients with severe deformities 1

Common Pitfalls to Avoid

• Inadequate NSAID trials: Must try at least two different NSAIDs at maximum tolerated dose for at least 3 months each before declaring treatment failure 2
• Premature discontinuation of TNF inhibitors: Results in high relapse rates (60-74%) 3
• Using systemic corticosteroids for axial disease: No evidence supports this and potential side effects are significant 1, 2
• Prescribing DMARDs for axial disease: These are ineffective for axial manifestations and delay appropriate TNF inhibitor therapy 1, 6
• Failing to assess cardiovascular and GI risk before NSAID prescription: NSAIDs carry significant toxicity that requires risk stratification 1
• Not continuing TNF inhibitor alone when effective: Adding NSAIDs or DMARDs to effective TNF inhibitor therapy is not recommended 3

Monitoring Strategy

Disease monitoring should include patient history (questionnaires including BASDAI), clinical parameters, laboratory tests (CRP, ESR), and imaging according to clinical presentation and ASAS core set 1, 2

Frequency of monitoring should be determined by symptom course, severity, and treatment intensity 1

Spinal radiographs should not be repeated more frequently than every 2 years unless clearly indicated 1