What is the recommended treatment for a patient with Ankylosing Spondylitis (nonsteroidal anti-inflammatory drugs (NSAIDs), tumor necrosis factor-alpha (TNF-alpha) inhibitors, etc.)?

Treatment of Ankylosing Spondylitis

NSAIDs are the first-line treatment for all patients with ankylosing spondylitis experiencing pain and stiffness, and for those with persistently active disease despite NSAIDs, TNF inhibitors should be initiated. 1

First-Line Pharmacological Treatment

NSAIDs as Initial Therapy

• NSAIDs are strongly recommended as first-line drug treatment for patients with AS presenting with pain and stiffness 1
• Continuous daily NSAID treatment is preferred over on-demand use in patients with persistently active, symptomatic disease 1
• No specific NSAID is superior to others—the choice should be based on individual gastrointestinal and cardiovascular risk profiles 1
• When prescribing NSAIDs, cardiovascular, gastrointestinal, and renal risks must be assessed 1

Important NSAID Considerations

• For patients with increased GI risk, consider COX-2 selective inhibitors (coxibs) or non-selective NSAIDs with gastroprotective agents 1
• NSAIDs carry significant side effect risks including serious gastrointestinal events (RR 5.36) 2
• Continuous NSAID therapy may retard radiographic disease progression, though this remains under investigation 1

Second-Line Treatment: Biologic Therapy

When to Initiate TNF Inhibitors

TNF inhibitors should be started when patients have persistently high disease activity despite adequate NSAID treatment 1

TNF Inhibitor Selection

• All TNF inhibitors (infliximab, adalimumab, etanercept, certolizumab, golimumab) are equally effective for axial disease—no single agent is preferred 1
• Exception: For patients with concomitant inflammatory bowel disease, TNF monoclonal antibodies (infliximab, adalimumab, certolizumab, golimumab) are strongly preferred over etanercept 1, 3
• There is no evidence requiring DMARD use before or during TNF inhibitor therapy for axial disease 1, 2

IL-17 Inhibitors as Alternative Biologics

• Secukinumab and ixekizumab are strongly recommended for patients with active AS despite NSAIDs 1
• TNF inhibitors are conditionally preferred over IL-17 inhibitors as first-line biologic therapy 1
• Secukinumab 150 mg demonstrated 61% ASAS20 response at Week 16 versus 28% with placebo 4

Treatment Failure and Switching Strategies

Primary Non-Response (No improvement after 3-6 months)

• Switch to secukinumab or ixekizumab rather than trying a different TNF inhibitor 1, 3

Secondary Non-Response (Loss of response after initial improvement)

• Switch to a different TNF inhibitor rather than switching to IL-17 inhibitors 1, 3
• Switching to a second TNF blocker may be beneficial, especially in patients with loss of response 1
• Do not switch to a biosimilar of the same TNF inhibitor that failed 1

Conventional DMARDs: Limited Role

Sulfasalazine and Methotrexate

• There is no evidence supporting efficacy of DMARDs (sulfasalazine, methotrexate) for axial disease 1
• Sulfasalazine may be considered only in patients with prominent peripheral arthritis 1
• Do not add sulfasalazine or methotrexate to TNF inhibitors for axial disease—continue TNF inhibitor monotherapy 1, 2

Tofacitinib

• Tofacitinib may be conditionally considered in patients with active AS despite NSAIDs, but only when TNF inhibitors are not available 1
• TNF inhibitors and IL-17 inhibitors are both preferred over tofacitinib 1

Glucocorticoids: Minimal Role

Systemic Glucocorticoids

• Systemic glucocorticoids are strongly recommended against for axial disease 1
• There is no evidence supporting their use for axial manifestations 1

Local Glucocorticoid Injections

• Corticosteroid injections directed to local sites of musculoskeletal inflammation may be considered 1
• For isolated active sacroiliitis despite NSAIDs, local parenteral glucocorticoids are conditionally recommended 1
• For active peripheral arthritis or enthesitis with stable axial disease, local injections are conditionally recommended 1

Duration and Discontinuation of Biologic Therapy

Long-Term Treatment Approach

• Biologic therapy should not be discontinued as standard practice—discontinuation results in relapses in 60-74% of patients 2, 3
• Dose tapering of biologics is conditionally recommended against 2
• Long-term continuous treatment is generally necessary to maintain disease control 2, 3
• Discontinuation might only be considered in patients with sustained remission for several years, with understanding that approximately two-thirds will relapse 2

Non-Pharmacological Treatment

Physical Therapy and Exercise

• Physical therapy is strongly recommended over no physical therapy 1
• Patient education and regular exercise are the cornerstone of non-pharmacological treatment 1
• Supervised exercises (land or water-based, individual or group) are more effective than home exercises alone 1
• Active physical therapy interventions are preferred over passive modalities 1

Surgical Interventions

Total Hip Arthroplasty

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

Spinal Surgery

• Spinal corrective osteotomy may be considered in patients with severe disabling deformity 1
• Acute vertebral fractures require consultation with a spinal surgeon 1

Monitoring Requirements

Disease Activity Monitoring

• Monitor validated AS disease activity measures (BASDAI or ASDAS) regularly 2, 3
• Monitor CRP or ESR every 3-4 months during biologic therapy 2, 3
• Frequency of monitoring should be individualized based on symptom course, severity, and treatment 1

Comorbidity Screening

• Be aware of increased cardiovascular disease risk and screen appropriately 1, 3
• Screen for osteoporosis as this comorbidity is increased in AS 1, 3

Extra-Articular Manifestations

Collaborative Management

• Psoriasis, uveitis, and inflammatory bowel disease should be managed in collaboration with respective specialists 1
• For patients with recurrent uveitis, consider this when selecting TNF inhibitors 1

Analgesics for Residual Pain

• Paracetamol and opioid-like drugs may be considered for residual pain after recommended treatments have failed, are contraindicated, or poorly tolerated 1
• These are not first-line agents and should only be used when other options are exhausted 5

Common Pitfalls to Avoid

• Do not use systemic glucocorticoids for axial disease—they lack evidence and are strongly recommended against 1
• Do not prescribe DMARDs (sulfasalazine, methotrexate) for axial symptoms—they are ineffective for axial disease 1
• Do not add DMARDs to TNF inhibitors for axial disease—monotherapy is preferred 1, 2
• Do not repeat spinal x-rays more frequently than every 2 years unless clearly indicated in individual cases 1
• Do not switch to a biosimilar of the same failed TNF inhibitor—this is strongly recommended against 1