Answers to Five Important Clinical Questions About Ankylosing Spondylitis

I'd like to thank Dr. Nigel Haroon for a great talk in London, Ontario. This is what I took away from his talk.

A young man comes to see you with a new diagnosis of Ankylosing Spondylitis (AS). He asks you, "Will my disease progress to full spinal fusion?" What do you tell him? We know approximately 60% of patients with AS will not progress over 5 years. That's good news. But ... 20% of patients will have more rapid radiographic progression. Is there a way to predict who will go on to progress radiographically?

The current predictors of radiographic progression include:

Pre-existing damage (bone formation): Ask for X-rays or an MRI to see if there are pre-existing syndesmophytes
Degree of inflammation: Measure the ESR and CRP. If they are elevated, the risk of radiographic progression increases
Smoking: Ask the patient about smoking status. There is evidence that relates smoking to disease progression.

His next question is - What causes the new bone formation in AS?Your answer - Nobody truly knows why bone forms in AS. Genes certainly play a role including HLA-B27, ERAP1, IL-23R, ANTXR2, TNFSF15, and TNFR1. However, genetics cannot possibly be the only factor. Environmental factors can contribute to bone formation and these include smoking and mechanical stress.

His third question is - "If we control my inflammation, can we prevent bone formation?" In other words, is new bone formation actually driven by inflammation? Clinical studies show patients with higher Ankylosing Spondylitis Disease Activity Scores (ASDAS) are more likely to have bone formation. Adding to this, MRI studies show syndesmophyte formation in areas of inflammation. Patients with MRI findings of inflammation at vertebral corners are more likely to develop syndesmophytes at these areas.

His fourth question - I’ve heard that taking regular NSAIDs can reduce the progression of my disease. Is this true?Your simple answer - NSAIDs do not reduce radiographic progression. Historical data has shown that NSAIDs reduced mSASSS change over time in patients with syndesmophytes and elevated time-averaged CRP. Therefore it was widely accepted that NSAIDs reduce radiographic progression and we told our patients this. However, in patients who did not have syndesmophytes with normal time-averaged CRP, NSAIDs had no effect on bone formation. Further support has come from a recent study in 2015. Joachim Sieger published a 2-year RCT of continuous NSAID use (average 112 mg/day) vs on-demand (66 mg/day) NSAID use. The higher NSAID group actually had more progression! So, there is no real proof that NSAIDs are truly disease modifying.

His fifth and final question - "Do TNF-inhibitors reduce radiographic progression?” Your answer - Absolutely. Early use of TNF-inhibitors reduces the rate of radiographic progression. The key is to use the medication early in the disease course (i.e. within 5-years).

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