What are the treatment options for non-radiographic axial spondyloarthritis (nr-axSpA)?

Non-Radiographic Axial Spondyloarthritis (nr-axSpA): Essential Information

What is nr-axSpA?

Non-radiographic axial spondyloarthritis is a chronic inflammatory disease affecting the spine and sacroiliac joints that shares all clinical features with ankylosing spondylitis but lacks the advanced joint damage visible on X-rays. 1

• Nr-axSpA and ankylosing spondylitis (AS) are now understood as two stages of the same disease spectrum called axial spondyloarthritis (axSpA) 1, 2
• The key distinguishing feature is the absence of radiographic sacroiliitis—advanced sacroiliac joint damage and spine ankylosis are not present 1
• Despite lacking X-ray changes, nr-axSpA causes similar levels of pain, stiffness, disease activity, and quality of life impairment as AS 3
• Approximately 10% of nr-axSpA patients will develop radiographic changes within 2 years, and this may exceed 80% after 20+ years 3

Clinical Features You Should Know

• Inflammatory back pain is the cardinal symptom: pain that improves with exercise, worsens with rest, and is particularly severe in the morning 4
• Morning stiffness of the spine with prolonged duration is typical 4
• 90-95% of patients are HLA-B27 positive 1, 4
• The disease can be accompanied by uveitis, psoriasis, and inflammatory bowel disease 1
• Diagnostic delay averages 5-7 years between first symptoms and diagnosis 4

Disease Burden and Prognosis

• Nr-axSpA imposes substantial physical and social burdens, interfering with work ability and schooling 1
• The severity of pain, stiffness, and limited flexibility varies widely among patients and over time 1
• While many patients manage well with conservative treatment, a minority experiences severe disabling symptoms requiring aggressive therapy 3

Treatment Algorithm

First-Line Treatment (Active Disease)

NSAIDs are strongly recommended as first-line pharmacological treatment and should be used continuously rather than on-demand for active disease. 1

• NSAIDs are highly effective against the major symptoms (pain and stiffness) and may have disease-modifying properties 2, 5
• Continuous NSAID use is conditionally recommended over on-demand use for active disease 1
• No particular NSAID is preferred over another 1
• Physical therapy is strongly recommended and should always be combined with pharmacological treatment 1
• Active physical therapy interventions (supervised exercise) are preferred over passive interventions (massage, ultrasound, heat) 1

Second-Line Treatment (Inadequate Response to NSAIDs)

TNF inhibitors are strongly recommended as the first biologic choice for active nr-axSpA despite NSAID treatment. 1

• This recommendation is based on high-quality evidence 1
• No particular TNF inhibitor is preferred over another 1
• TNF inhibitors are conditionally recommended over IL-17 inhibitors (secukinumab or ixekizumab) as first-line biologic therapy 1
• TNF inhibitors are conditionally recommended over tofacitinib 1

Alternative Biologics

IL-17 inhibitors (secukinumab or ixekizumab) are conditionally recommended for active nr-axSpA despite NSAIDs, but are second-choice after TNF inhibitors. 1

• Secukinumab or ixekizumab are preferred over tofacitinib 1
• When TNF inhibitors are contraindicated, secukinumab or ixekizumab are conditionally recommended over sulfasalazine, methotrexate, or tofacitinib 1

Treatment Failure Algorithm

If the first TNF inhibitor fails due to primary non-response (never worked), switch to secukinumab or ixekizumab rather than trying a second TNF inhibitor. 1

• If the first TNF inhibitor fails due to secondary non-response (worked initially then stopped), switch to a different TNF inhibitor rather than a non-TNF biologic 1
• Do not switch to the biosimilar of the first TNF inhibitor if that TNF inhibitor failed—this is strongly recommended against 1

What NOT to Do (Common Pitfalls)

Do not add methotrexate or sulfasalazine to TNF inhibitor therapy—this combination is conditionally recommended against in favor of switching to a different biologic 1

• Systemic glucocorticoids are strongly recommended against for axial symptoms 1
• Sulfasalazine, methotrexate, and tofacitinib are only conditionally recommended over no treatment for active nr-axSpA despite NSAIDs, and only when biologics are not appropriate 1
• Sulfasalazine is recommended only for persistent peripheral arthritis when TNF inhibitors are contraindicated 1

Stable Disease Management

For patients with stable nr-axSpA, use on-demand NSAIDs rather than continuous treatment. 1

• Do not discontinue or taper biologics in patients with stable disease—this is conditionally recommended against 1, 6
• If receiving both TNF inhibitor and NSAIDs, continue TNF inhibitor alone rather than both medications 1
• If receiving both TNF inhibitor and a conventional synthetic antirheumatic drug, continue TNF inhibitor alone 1

Local Injection Therapy

• For isolated active sacroiliitis despite NSAIDs, local glucocorticoids are conditionally recommended 1
• For active enthesitis despite NSAIDs, locally administered parenteral glucocorticoids are conditionally recommended, but avoid peri-tendon injections of Achilles, patellar, and quadriceps tendons 1
• For active peripheral arthritis despite NSAIDs, locally administered parenteral glucocorticoids are conditionally recommended 1

Imaging Considerations

MRI of the spine or pelvis can aid assessment when disease activity is unclear, but routine monitoring with serial spine radiographs is not recommended. 1

• MRI has made identification of nr-axSpA possible by detecting inflammation before radiographic damage occurs 7
• Spine MRI is considered positive for axial spondyloarthritis if three or more sites of inflammatory spondylitis are present 8
• Contrast enhancement is not necessary for diagnosis 8
• Much research is still needed regarding optimal MRI use, including distinguishing normal population changes from pathology 7

Treatment Goals

The primary goals are to alleviate symptoms, improve functioning, maintain work ability, decrease disease complications, and forestall skeletal damage as much as possible 1