What is the recommended therapy for ankylosing spondylitis?

Treatment of Ankylosing Spondylitis

Start with NSAIDs as first-line therapy, and if disease remains active despite adequate NSAID trial, advance to TNF inhibitors as the preferred biologic, with IL-17 inhibitors (secukinumab or ixekizumab) reserved for TNF inhibitor failures or specific contraindications. 1

First-Line Pharmacologic Treatment

NSAIDs

• Strongly recommend NSAIDs over no treatment for all patients with active ankylosing spondylitis (AS) 1
• Conditionally recommend continuous NSAID therapy over on-demand use in patients with active disease, primarily for controlling disease activity 1
• No particular NSAID is preferred over another—choice should be based on patient response, tolerability, and comorbidities (particularly gastrointestinal, renal, and cardiovascular disease) 1

Second-Line Treatment: Biologic DMARDs

When to Advance to Biologics

Initiate biologic therapy when patients have: 1, 2, 3

• Active disease (BASDAI ≥4 or ASDAS ≥2.1) for at least 4 weeks
• Failed adequate trial of at least 2 NSAIDs over 3 months
• AND at least one of: elevated CRP, definite MRI inflammation of sacroiliac joints, or radiographic sacroiliitis

TNF Inhibitors (First Choice Biologic)

• Strongly recommend TNF inhibitors over no biologic treatment in patients with active AS despite NSAIDs (high-quality evidence) 1
• Conditionally recommend TNF inhibitors over IL-17 inhibitors as initial biologic choice 1
• No specific TNF inhibitor is preferred—options include infliximab, etanercept, adalimumab, certolizumab, golimumab, and their biosimilars 1
• TNF monoclonal antibodies (infliximab, adalimumab, certolizumab, golimumab) are preferred for patients with recurrent uveitis or inflammatory bowel disease 1, 3

IL-17 Inhibitors (Secukinumab or Ixekizumab)

• Strongly recommend secukinumab or ixekizumab over no treatment in patients with active AS despite NSAIDs (high-quality evidence) 1
• Preferred over TNF inhibitors in patients with heart failure or demyelinating disease as contraindications to TNF inhibitors 1
• Preferred over TNF inhibitors in patients with significant psoriasis 3
• Conditionally recommend secukinumab or ixekizumab over switching to another TNF inhibitor in patients with primary non-response to first TNF inhibitor 1

Limited Role Therapies

Conventional Synthetic DMARDs

• Sulfasalazine or methotrexate should be considered ONLY in patients with prominent peripheral arthritis or when TNF inhibitors are unavailable 1
• Sulfasalazine has minimal benefit for axial symptoms but may help peripheral arthritis 1
• Methotrexate evidence is weak, based on low-dose studies showing no axial benefit 1

JAK Inhibitors (Tofacitinib)

• Conditionally recommend tofacitinib as a potential option for patients with contraindications to TNF inhibitors (other than infections) 1
• TNF inhibitors and IL-17 inhibitors are preferred over tofacitinib 1
• Phase II data showed benefit, but phase III results were pending at time of guideline publication 1

Therapies NOT Recommended

• Strongly recommend AGAINST systemic glucocorticoids for axial disease 1
• Leflunomide, apremilast, thalidomide, and pamidronate are not recommended 1

Treatment Failure Management

After First TNF Inhibitor Failure

Primary non-response (no improvement within 3-6 months): 1

• Conditionally recommend switching to secukinumab or ixekizumab over switching to another TNF inhibitor

Secondary non-response (loss of response after initial benefit): 1

• Conditionally recommend switching to a different TNF inhibitor over switching to a non-TNF biologic

Important Caveat

• Strongly recommend AGAINST switching to a biosimilar of the first TNF inhibitor after treatment failure 1
• Conditionally recommend AGAINST adding sulfasalazine or methotrexate to a failing TNF inhibitor—switch to a new biologic instead 1

Stable Disease Management

Biologic Continuation

• Conditionally recommend AGAINST discontinuation of biologics in patients with stable disease due to high likelihood of symptom recurrence 1, 3
• Conditionally recommend AGAINST dose tapering as a standard approach 1
• If tapering is considered, counsel patients about potential for increased disease activity 1

Concomitant Medications

• Conditionally recommend AGAINST co-treatment with low-dose methotrexate in patients on TNF inhibitors 1
• Conditionally recommend continuing TNF inhibitor alone rather than continuing both TNF inhibitor and NSAIDs or conventional synthetic DMARDs 1
• In stable disease, conditionally recommend on-demand NSAIDs over continuous NSAIDs 1

Biosimilar Switching

• Strongly recommend continuing originator TNF inhibitor over mandated switching to biosimilar in patients with stable disease on an originator product 1

Non-Pharmacologic Management

Physical Therapy

• Strongly recommend physical therapy over no physical therapy for all patients with AS 1, 3
• Conditionally recommend active/supervised exercise over passive interventions (massage, ultrasound, heat) 1
• Conditionally recommend land-based over aquatic therapy 1
• Conditionally recommend unsupervised back exercises for ongoing maintenance 1

Patient Education and Safety

• Conditionally recommend participation in formal self-management education programs 1
• Conditionally recommend fall evaluation and counseling 1
• Strongly recommend AGAINST spinal manipulation in patients with spinal fusion or advanced spinal osteoporosis 1

Surgical Considerations

• Strongly recommend total hip arthroplasty for patients with advanced hip arthritis 1
• Conditionally recommend AGAINST elective spinal osteotomy for severe kyphosis 1

Key Clinical Pitfalls

Common errors to avoid:

• Do not use sulfasalazine or methotrexate for pure axial disease—they lack efficacy for spinal symptoms 1
• Do not use systemic glucocorticoids for axial inflammation—they are ineffective and carry significant risks 1
• Do not switch from an originator TNF inhibitor to its biosimilar after treatment failure—this is futile 1
• Do not use etanercept in patients with inflammatory bowel disease or recurrent uveitis—TNF monoclonal antibodies are superior 1, 3
• Do not use IL-17 inhibitors in patients with inflammatory bowel disease—they may worsen IBD 1