What is the recommended treatment approach for ankylosing spondylitis, including first‑line therapy and subsequent options?

Treatment of Ankylosing Spondylitis

NSAIDs are the first-line pharmacological treatment for ankylosing spondylitis, combined with mandatory patient education and regular exercise throughout the disease course. 1, 2

Initial Treatment Approach

Non-Pharmacological Foundation (Start Immediately)

• Patient education and regular exercise must be initiated at diagnosis and continued indefinitely, as level Ib evidence demonstrates home exercise improves function in the short term 1, 2
• Group physical therapy produces superior patient global assessment outcomes compared to home exercise alone, though both improve function 1, 2
• Individual or group physical therapy should be incorporated based on patient preference and access 1
• Patient associations and self-help groups provide additional support, though formal outcome data are limited 1

First-Line Pharmacological Treatment: NSAIDs

• NSAIDs should be prescribed as the initial drug therapy for all patients with pain and stiffness, with level Ib evidence showing improvement in spinal pain, peripheral joint pain, and function within 6 weeks 1, 2
• Continuous daily NSAID therapy is preferred over intermittent "on-demand" use for patients with persistently active disease, as one randomized controlled trial demonstrated that continuous celecoxib treatment retarded radiographic disease progression at 2 years 1, 2
• No single NSAID preparation has proven superior to others in comparative studies 1

NSAID Selection Based on GI Risk

• For patients with increased gastrointestinal risk factors (age >65, prior GI bleeding, concomitant corticosteroids), prescribe either a selective COX-2 inhibitor OR a non-selective NSAID plus gastroprotective agent 1, 2
• NSAIDs carry a relative risk of 5.36 for serious GI bleeding events, which is dose-dependent 1, 3
• COX-2 inhibitors reduce serious GI events by 82% compared to non-selective NSAIDs (RR 0.18) 1
• Consider cardiovascular risk factors when selecting between COX-2 inhibitors and traditional NSAIDs, as emerging evidence suggests both classes may carry cardiovascular toxicity 1

Second-Line Options for NSAID-Refractory or Intolerant Patients

Analgesics for Inadequate NSAID Response

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

Local Corticosteroid Injections

• Corticosteroid injections directed to specific sites of musculoskeletal inflammation (enthesitis, peripheral joints) should be considered for localized symptoms 1
• Systemic corticosteroids have no evidence supporting their use for axial disease and should be avoided 1

Disease-Modifying Antirheumatic Drugs (DMARDs)

• There is no evidence supporting DMARD efficacy (including sulfasalazine and methotrexate) for axial disease manifestations 1
• Sulfasalazine may be considered specifically for patients with peripheral arthritis, as it shows benefit in this subset 1

Biological Therapy: Anti-TNF Agents

Indications for Anti-TNF Therapy

• Anti-TNF treatment should be initiated in patients with persistently high disease activity despite adequate trials of conventional NSAID treatment, following ASAS recommendations 1, 2
• There is no evidence requiring DMARD use before or concomitant with anti-TNF therapy for patients with purely axial disease 1, 2
• All TNF inhibitors (infliximab, etanercept, adalimumab) demonstrate equivalent efficacy with level Ib evidence showing large treatment effects sustained over at least 6 months 2

Disease Monitoring Strategy

• Monitor using patient history (standardized questionnaires), clinical parameters, laboratory tests (ESR, CRP), and imaging according to the ASAS core set 1, 2, 4
• Frequency of monitoring should be individualized based on symptoms, disease severity, and current drug treatment 1
• Spinal radiographs should not be repeated more frequently than every 2 years unless specific clinical indications arise 2, 4

Surgical Interventions for Advanced Disease

• Total hip arthroplasty should be considered for patients with refractory pain or disability plus radiographic evidence of structural hip damage, regardless of age 1, 2, 4
• Spinal corrective osteotomy and stabilization procedures may benefit selected patients with severe disabling deformity or segmental instability 1, 2, 4

Treatment Algorithm Summary

1. Immediate initiation: Patient education + regular exercise program + NSAIDs (continuous dosing preferred)
2. NSAID selection: Base on GI/CV risk profile (COX-2 inhibitor or non-selective NSAID + gastroprotection for high-risk patients)
3. Inadequate NSAID response: Add analgesics, consider local corticosteroid injections for peripheral/entheseal involvement
4. Peripheral arthritis: Add sulfasalazine
5. Persistently high disease activity: Initiate anti-TNF therapy (no DMARD requirement for axial disease)
6. Structural damage with disability: Surgical consultation for arthroplasty or spinal procedures

Critical Pitfalls to Avoid

• Do not use systemic corticosteroids for axial symptoms, as there is no supporting evidence 1
• Do not prescribe DMARDs for purely axial disease, as they lack efficacy for spinal manifestations 1
• Do not require DMARD trials before initiating anti-TNF therapy in axial disease, as this delays effective treatment without evidence of benefit 1, 2
• Do not use intermittent "on-demand" NSAID dosing in patients with persistently active disease, as continuous therapy may provide disease-modifying effects 1, 2