What are the treatment options for ankylosing spondylitis?

Treatment Options for Ankylosing Spondylitis

NSAIDs are the first-line pharmacological treatment for all patients with ankylosing spondylitis experiencing pain and stiffness, and should be used continuously at full doses rather than on-demand for patients with persistently active disease. 1

Initial Treatment Approach

Non-Pharmacological Therapy (Essential Foundation)

• Physical therapy and regular exercise are strongly recommended as fundamental components of treatment and should be initiated immediately upon diagnosis. 1
• Individual and group physical therapy programs should be prescribed, with home exercise programs effective for ongoing management. 1
• Patient education regarding disease course, treatment expectations, and self-management strategies is a core component of care. 1

First-Line Pharmacological Treatment: NSAIDs

• NSAIDs are strongly recommended as first-line drug therapy for patients with pain and stiffness, with continuous daily use preferred over on-demand dosing for those with persistently active disease. 1
• Approximately 75% of AS patients demonstrate good or very good response to full-dose NSAIDs within 48 hours, distinguishing inflammatory from mechanical back pain. 1
• If the first NSAID fails after 2-4 weeks at adequate doses, switch to a different NSAID before concluding NSAID failure. 2
• For patients with gastrointestinal risk factors, use either non-selective NSAIDs with gastroprotective agents or selective COX-2 inhibitors. 1
• Continuous NSAID therapy may slow radiographic progression and syndesmophyte formation, providing disease-modifying effects beyond symptom control. 3

Medications to Avoid

• Systemic corticosteroids are strongly not recommended for axial disease due to lack of efficacy. 1
• Local corticosteroid injections may be considered for peripheral arthritis or enthesitis, but not for axial symptoms. 1
• Traditional DMARDs (sulfasalazine, methotrexate) have no efficacy for axial disease, though sulfasalazine may be considered for peripheral arthritis only. 1

Second-Line Treatment: TNF Inhibitors

Indications for Anti-TNF Therapy

• TNF inhibitors are strongly recommended for patients with persistently high disease activity despite adequate NSAID treatment. 1
• This represents patients who have failed at least two different NSAIDs at full doses for adequate duration (typically 2-4 weeks each). 2

Choice of TNF Inhibitor

• No particular TNF inhibitor is preferred for uncomplicated axial disease—all are equally effective (etanercept, infliximab, adalimumab, certolizumab, golimumab). 1, 4
• For patients with concomitant inflammatory bowel disease, TNF monoclonal antibodies (infliximab, adalimumab, certolizumab, golimumab) are strongly preferred over etanercept. 1, 5
• For patients with recurrent uveitis, TNF monoclonal antibodies should similarly be preferred over etanercept. 1

Duration and Dosing of TNF Inhibitors

• Long-term continuous treatment with TNF inhibitors is conditionally recommended, as discontinuation results in relapse in 60-74% of patients. 4
• Discontinuation should only be considered in patients with sustained remission for several years, with understanding that two-thirds will relapse. 4
• Dose tapering is conditionally recommended against as a standard approach. 4
• TNF inhibitors should be used as monotherapy—combination with methotrexate or other DMARDs is not recommended for axial disease. 4

Dosing Specifics from FDA Labels

• Adalimumab (Humira): 40 mg subcutaneously every other week for AS. 6
• Etanercept (Enbrel): 50 mg subcutaneously once weekly for AS. 7

Switching Biologics

• For primary non-response to first TNF inhibitor, switching to secukinumab or ixekizumab is conditionally recommended over trying a second TNF inhibitor. 4
• For secondary non-response (loss of efficacy over time), switching to a different TNF inhibitor is conditionally recommended. 4

Surgical Interventions

Hip Arthroplasty

• Total hip arthroplasty is strongly recommended for patients with refractory pain or disability and radiographic evidence of advanced hip arthritis, regardless of age. 1

Spinal Surgery

• Corrective osteotomy and stabilization procedures may be valuable in selected patients with severe spinal deformities or instability. 1

Monitoring and Disease Assessment

• Disease monitoring should include patient history, clinical parameters (pain, function, spinal mobility), laboratory tests (CRP, ESR), and imaging according to clinical presentation. 1
• Regular monitoring of CRP or ESR is conditionally recommended for patients on biologic therapy. 4
• Treatment goals should be predefined between patient and physician, with clinical remission or inactive disease as the primary target. 2
• Frequency of monitoring should be individualized based on disease activity and treatment intensity. 1

Important Safety Considerations

NSAID Toxicity

• NSAIDs carry significant gastrointestinal risks (RR 5.36 for serious GI events) and potential cardiovascular effects. 1
• Long-term continuous NSAID use requires careful monitoring for GI and cardiovascular complications. 3

TNF Inhibitor Risks

• Patients on TNF inhibitors have increased risk of serious infections including tuberculosis reactivation, invasive fungal infections, and opportunistic infections. 6, 7
• Test for latent tuberculosis before initiating TNF inhibitors and monitor closely during therapy. 6, 7
• Lymphoma and other malignancies have been reported, particularly hepatosplenic T-cell lymphoma in young males receiving concomitant azathioprine or 6-mercaptopurine. 6, 7
• Common adverse effects include injection site reactions (RR 3.12) and development of antinuclear antibodies (RR 2.38). 4

Common Pitfalls to Avoid

• Do not discontinue NSAIDs once clinical improvement is achieved—continuous use may provide disease-modifying effects. 3
• Do not use traditional DMARDs as a bridge to biologics for axial disease—they are ineffective and delay appropriate treatment. 1
• Do not require DMARD failure before initiating TNF inhibitors in axial disease—this is only relevant for peripheral arthritis. 1
• Do not use systemic corticosteroids for axial symptoms—they lack efficacy and add toxicity. 1