How Important is Early Therapy in Axial Spondyloarthritis?

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Introduction

Currently there are mainly 2 groups of drugs that have been shown effective in the treatment of patients with axSpA, NSAIDs and TNF-α blockers, which have been approved for those patients who do not adequately respond to NSAID treatment.1 Conventional disease-modifying antirheumatic drugs and some other biologics, such as anakinra2 and abatacept,3 have not been shown so far to be clinically efficacious in this disease.

Most of the early treatment trials in axSpA have been performed in patients with ankylosing spondylitis (AS) classified according to the modified New York criteria—implying that patients already had structural changes in the SI joints (radiographic sacroiliitis). The mean symptom duration of patients included in treatment trials both with NSAIDs and TNF blockers has been between 10 and 14 years. Although short symptom duration and young age have been identified as parameters predictive of good response rates,4 there were, until recently, no data available addressing the question of whether axSpA patients respond better when treated earlier. The development of the ASAS classification criteria for axSpA5 was a big step forward in that regard because they allow including patients in treatment trials at an early phase of their disease before the occurrence of radiographic changes in the SI joints. This group has recently be termed as nonradiographic axSpA (nr-axSpA). The ASAS classification criteria for the whole group of axSpA are fulfilled if patients have chronic back pain greater than 3 months, if symptoms start at an age younger than 45 years, and if they have either active inflammation in the SI joints on MRI plus 1 additional clinical or laboratory feature typical of SpA, or if they are positive for HLA-B27 plus 2 additional other SpA features.

This overview discusses the available data on whether early treatment strategies in patients with axSpA have an effect on (1) the percentage of patients reaching clinical remission, (2) achieving drug-free remission, and (3) the progress of radiographic progression in the spine as a parameter for structural damage.

Section snippets

The effect of anti-TNF therapy on clinical parameters depends on symptom duration

This article focuses on clinical remission rates according to the ASAS definition6 but also reports on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% and/or ASAS 40% response rates6 if data on remission are not available. These data are summarized in Table 1. Clinical remission was reached in TNF blocker trials in approximately 25% of patients with established AS,7, 8, 9 but AS patients with a symptom duration of less than 10 years showed a better response rate than patients

The effect of NSAID therapy on clinical parameters also depends on symptom duration

The vast majority of NSAID trials have been performed in patients with established AS, and remission rates between 11% and 15% are reported.6, 17, 18 As discussed previously, in the only early study performed in patients with axSpA (symptom duration <3 years), a remission rate of 33% was found.16 These results indicate that an early and consequent treatment with NSAIDs (patients in this study were treated with naproxen 1000 mg/d for 28 weeks) in active axSpA patients seems effective and that

Potential effect of early treatment on reaching drug-free remission

In all TNF blocker trials performed in patients with axSpA so far, the relapse rates after drug withdrawal were high, indicating a chronic inflammatory disease and that TNF blocker therapies are not curative. Nonetheless, although there were only minor differences in the relapse rates reported in these trials, a shorter symptom duration may have some effect on these rates: in patients with a symptom duration greater than 10 years,19 7 to 8 years,20 2.9 years,21 or 15 months,22 a clinical

Potential effect of early treatment on stopping or retarding structural progression

Structural progression has been quantified in nearly all axSpA studies by measuring structural damage in the spine, most often by applying the Modified Stroke Ankylosing Spondylitis Spinal Score (mSASSS),24 which is predominantly but not exclusively a score for new bone formation. Although NSAIDs seem to have a retarding effect on radiographic progression in AS patients25, 26, 27 (discussed in more detail by Poddubnyy and colleagues elsewhere in this issue), this seems not to be the case in

What is the optimal strategy in the management of patients with axSpA?

There are at least 2 areas of discussion. The first question is, Which is more important—identifying patients with axSpA at any disease stage, concentrating on inflammation regardless of symptom duration and treating whenever there is evidence of that, or trying to detect patients with axSpA as early as possible to suppress inflammation as early as possible? These strategies are not exclusive, and the former is clinical routine in most rheumatologic settings around the world. In an analogy to

Summary

There is growing evidence that patients with axSpA respond better to TNF blocker therapy if started early. This is not only the case for patients with AS but also for those with nr-axSpA. Which part of the complaints in the subgroup of axSpA patients with longstanding disease, with low grade of structural damage and with low grade of inflammation as detected by CRP and MRI can be explained by fibromyalgia has yet to be investigated. Treatment with NSAIDs seems to result in superior improvement

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