Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line of treatment in patients with AS. It has a rapid onset of action and we can identify responders within a few days to weeks. For a proportion of patients, NSAIDs may be the only treatment required. Apart from symptomatic relief, regular NSAID dosing seems to reduce radiographic progression although the data for this in not strong. Of concern is the cardiovascular risk profile of these agents. The cardiovascular risk increases with COX-2 selectivity with more selective agents such as rofecoxib being associated with greater pooled risk of CV events.¹ Naprosyn appears to be among the safest of NSAIDs in this regard. The antiplatelet action of Naprosyn may be an added advantage here. Interestingly diclofenac has greater COX-2 selectivity than celecoxib and a higher risk of cardiovascular events than most NSAIDs. Yet, diclofenac is the most commonly prescribed NSAID around the world.² We need to closely look at this literature and make changes in our practice. The advantage in AS is that most patients are young and have relatively lower cardiovascular risk than patients with other conditions like RA.

Non-radiographic axial spondyloarthritis (nrAxSpA) was proposed as a disease entity by ASAS, although the concept has been around for a long time. Professors Ashok Kumar and Anand Malaviya had studied the progression of spondyloarthritis patients who did not satisfy the modified New York Criteria and published their findings after a median follow up of 11 years in 2001.³ For the purpose of classification, patients who do not meet the modified New York criteria should ideally go for MRI although technically they can satisfy the clinical arm if they are HLA-B27 positive. The importance of MRI lies in the fact that the specificity of the MRI arm is better than the clinical arm. More important, the response to TNF-inhibitor therapy is better in patients with MRI evidence of SpA than those satisfying the clinical arm, especially if their CRP is normal.

The ideal spondyloarthritis sequences for MRI include a T1 sequence for structural changes and a STIR sequence for inflammation. It is also important to visualize the entire spine including lateral elements as inflammation may be localized to small areas like facet joints and costovertebral junctions. However, in the ASAS classification criteria for nrAxSpA, only the SI joint MRI is considered.

It is still debated if JoAS and AoAS are part of the same spectrum or separate diseases. JoAS patients have less axial involvement and more peripheral arthritis as well as possibly uveitis. Functional disability has been variably reported as being worse in adult or juvenile onset AS. Spinal radiographic abnormalities are more marked in AoAS while hip disease is worse in JoAS. The delay in diagnosis is thought to be higher in JoAS.⁴

Although response to TNF inhibitors is expected to be same in JoAS and AoAS, a recent RCT did not show significant difference from placebo in ASAS40 response at 12 weeks.

Unfortunately, for axial disease there is no effective treatment currently approved for treatment for AS. Sulfasalazine appears to reduce spinal pain in patients with shorter duration of symptoms indicating possible efficacy in early disease. CRP and ESR also seem to reduce. However in none of the sulfasalazine trials in AS, the primary end point of BASDAI response was met. Pamidronate has been tried but the clinical experience has not been great despite positive results in an RCT.⁵. Newer agents like apremilast and IL-17 inhibition appear to be effective from preliminary studies. It remains to be seen how expensive these medications will be in the long run. One would have expected apremilast, being an oral small molecule, would be cheaper, but that does not seem to be the case.

There is an estimated 50% increase in mortality in AS patients compared to the general population. The SMR was 1.6 in a cohort of 836 patients with 1.6 and 1.72 being the RR of cardiovascular and cerebrovascular death. ⁶ Earlier studies have reported amyloidosis as the most common cause of death while more recent studies show cardiovascular disease predominates. There is a correlation between the levels of inflammation as assessed by ESR/CRP and clinically by enthesitis with the risk of mortality. Other proposed mechanisms include altered lipid profile, use of NSAIDs, hypertension and thrombocytosis.

There is currently no direct proof that the use of TNF-inhibitors have reduced mortality in AS. However, some extrapolations can be made from clinical and laboratory observations. TNF-inhibitors are very effective in reducing inflammation and bringing symptomatic improvement of patients. By reducing inflammation and increasing the ability of patients to do exercises, TNF-inhibitors are likely to reduce cardiovascular morbidity and mortality. A direct effect of TNF-inhibitors in reducing the atherogenic potential of lipids has been proposed. The requirement of NSAIDs decreases, although interestingly in an older study, NSAID use was associated with decreased mortality. Microvascular dysfunction improves after TNF-inhibitor therapy. Finally effects on platelet activity have been demonstrated. Although many of these observations have not been replicated there appears to be a trend towards lowering of overall cardiovascular risk with TNF-inhibitor therapy.