What is the recommended treatment approach for ankylosing spondylitis?

Treatment of Ankylosing Spondylitis

First-Line Pharmacological Treatment: NSAIDs

NSAIDs are the cornerstone first-line pharmacological treatment for all patients with ankylosing spondylitis who have pain and stiffness, with strong evidence demonstrating improvement in spinal pain, peripheral joint pain, and function. 1, 2

NSAID Dosing Strategy

• Continuous daily NSAID therapy is preferred over intermittent "on-demand" use for patients with persistently active, symptomatic disease, as emerging evidence suggests continuous treatment may retard radiographic disease progression at 2 years. 1, 2
• Intermittent NSAID use is conditionally recommended only for patients with stable disease or infrequent symptoms. 1
• Level Ib evidence demonstrates NSAIDs improve spinal pain, peripheral joint pain, and function over 6 weeks. 1, 2

NSAID Selection Based on GI Risk

• For patients with increased gastrointestinal risk (age >65, prior GI bleeding, concurrent corticosteroids), prescribe either:
  • A selective COX-2 inhibitor alone, OR
  • A non-selective NSAID plus a gastroprotective agent (PPI or misoprostol). 1, 2
• Selective COX-2 inhibitors reduce serious GI events by 82% compared to non-selective NSAIDs (RR 0.18,95% CI 0.14-0.23). 1
• Non-selective NSAIDs carry a relative risk of 5.36 for serious GI bleeding. 1

Important NSAID Caveats

• No individual NSAID has demonstrated superiority over others in head-to-head trials. 2
• Cardiovascular risk must be considered when selecting between COX-2 inhibitors and traditional NSAIDs, as both classes may have cardiovascular toxicity. 1

Non-Pharmacological Treatment (Mandatory Concurrent Therapy)

Physical therapy and regular exercise must be initiated immediately and continued throughout the disease course as foundational treatment. 1, 2

• Level Ib evidence supports home exercise improving function in the short term. 2
• Group physical therapy demonstrates superior patient global assessment outcomes compared to home exercise alone. 2
• Patient education should be provided at diagnosis and reinforced regularly. 1, 2

Second-Line Pharmacological Treatment: Anti-TNF Biologics

Anti-TNF therapy should be initiated in patients with persistently high disease activity despite adequate NSAID trials, following ASAS recommendations. 1, 2

When to Initiate Anti-TNF Therapy

• Start anti-TNF biologics when patients have persistently high disease activity despite conventional NSAID treatment at adequate doses. 1, 2
• There is no evidence requiring DMARD use before or concomitant with anti-TNF therapy for axial disease—DMARDs can be omitted entirely. 1, 2
• Patients receiving TNFi should continue TNFi alone rather than adding NSAIDs or conventional DMARDs. 1

Anti-TNF Agent Selection

• All TNF inhibitors (infliximab, etanercept, adalimumab) show equivalent efficacy for axial and articular/entheseal manifestations with large treatment effects over at least 6 months. 2
• For patients with recurrent iritis, TNFi monoclonal antibodies (infliximab, adalimumab) are preferred over etanercept. 1
• For patients with inflammatory bowel disease, TNFi monoclonal antibodies are strongly preferred over etanercept. 1, 2

Anti-TNF Dosing (Infliximab Example)

• Infliximab: 5 mg/kg IV at weeks 0,2, and 6, then every 6 weeks for maintenance. 3
• Biosimilar switching: Strongly recommend continuing originator TNFi over mandated switching to biosimilar. 1

Anti-TNF Continuation Decisions

• Conditionally recommend against discontinuation of biologics in patients receiving treatment. 1
• Conditionally recommend against dose tapering as a standard approach. 1

Role of Conventional DMARDs

Conventional DMARDs (sulfasalazine, methotrexate) have no evidence of efficacy for axial disease and should not be used for spinal manifestations. 1, 2

• Sulfasalazine may be considered only for patients with peripheral arthritis, where it has demonstrated benefit. 1, 2
• Low-dose methotrexate co-treatment with TNFi is not recommended. 1

Adjunctive Therapies

Analgesics

• Paracetamol (acetaminophen) and opioids may be added for pain control when NSAIDs are insufficient, contraindicated, or poorly tolerated. 1, 2

Corticosteroids

• Local corticosteroid injections directed to enthesitis sites or peripheral joints are appropriate for localized musculoskeletal inflammation. 1, 2
• Systemic corticosteroids for axial disease are not supported by evidence and should be avoided. 1, 2

Disease Monitoring

Disease monitoring should include patient-reported outcomes (standardized questionnaires), clinical examination, laboratory markers (ESR, CRP), and imaging according to the ASAS core set. 1, 2

• Conditionally recommend regular-interval use and monitoring of validated AS disease activity measures. 1
• Conditionally recommend regular CRP or ESR monitoring. 1
• Spinal radiographs should not be repeated more frequently than every 2 years unless clearly indicated. 2
• Monitoring frequency should be determined by symptom burden, disease severity, and current pharmacologic regimen. 1, 2

Management of Extra-Articular Manifestations

Acute Iritis

• Strongly recommend treatment by an ophthalmologist to decrease severity, duration, or complications. 1
• For recurrent iritis, conditionally recommend prescription of topical glucocorticoids for prompt at-home use. 1
• TNFi monoclonal antibodies are preferred over other biologics for recurrent iritis. 1

Inflammatory Bowel Disease

• No particular NSAID is preferred to decrease risk of worsening IBD symptoms. 1
• TNFi monoclonal antibodies are conditionally recommended over other biologics. 1

Surgical Interventions

Hip Arthroplasty

• Total hip arthroplasty is strongly recommended for patients with refractory pain or disability and radiographic evidence of structural hip damage, independent of age. 1, 2

Spinal Surgery

• Spinal corrective osteotomy and stabilization procedures may be valuable in selected patients with severe kyphosis or deformity. 1, 2
• In adults with severe kyphosis, conditionally recommend against elective spinal osteotomy due to risks. 1
• In adults with spinal fusion or advanced spinal osteoporosis, strongly recommend against spinal manipulation. 1

Screening Recommendations

• Conditionally recommend screening for osteopenia/osteoporosis with DXA scan. 1
• In adults with syndesmophytes or spinal fusion, conditionally recommend DXA scan of both spine and hips. 1
• Conditionally recommend fall evaluation and counseling. 1
• Strongly recommend against screening for cardiac conduction defects with routine ECG. 1

Common Pitfalls to Avoid

• Do not delay anti-TNF therapy by requiring failed DMARD trials in purely axial disease—this is not evidence-based. 1, 2
• Do not use systemic corticosteroids for axial symptoms—they lack efficacy and add toxicity. 1, 2
• Do not use intermittent NSAIDs in patients with persistently active disease—continuous therapy is superior for symptom control and may slow radiographic progression. 1, 2
• Do not prescribe methotrexate or sulfasalazine for axial disease—reserve sulfasalazine only for peripheral arthritis. 1, 2