Challenges of Targeting Remission in Axial Spondyloarthritis

The increasing use of biologic therapies as the standard of care in several disease states has raised expectations for treatment outcomes. The treatment of axial spondyloarthritis (axSpA) is no exception. Targeted biologic therapies have been developed for axSpA with adequate safety and efficacy measures and have significantly improved clinical outcomes compared with conventional treatment options. Several guidelines recommend their clinical use, including guidelines published by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis,¹ the European League Against Rheumatism (EULAR),² and most recently, joint guidelines developed by the American College of Rheumatology and the National Psoriasis Foundation.³

Biologics, such as tumor necrosis factor inhibitors, reduce pain, improve function, decrease inflammation, and have recently been shown to reduce disease progression in axSpA.^4,5 These impressive results have changed the expectations of axSpA treatment goals and outcomes. With a focus on aggressive treat-to-target strategy, as demonstrated in the TOPICA trial,⁶ clinical remission is now the expected treatment goal for inflammatory joint diseases such as axSpA. The challenge, however, is the current lack of a universally accepted definition of remission for axSpA, and the assessment tools currently available are inadequate to assess clinical remission. A recent review published in The Journal of Rheumatology by Baraliakos and colleagues summarize the challenges of defining and assessing clinical remission in axSpA.⁷

Although current guidelines define remission as the absence of clinical and laboratory evidence of significant inflammatory disease,^8,9 the parameters against which axSpA is assessed to demonstrate clinical remission are unclear. Tools that are currently used to assess axSpA disease activity have been proposed for the assessment of clinical remission, including the Assessment of Spondyloarthritis international Society partial remission (ASAS PR), the Bath Ankylosing Spondylitis Disease Activity Index, and the Ankylosing Spondylitis Disease Activity Score (ASDAS).⁷ Although these tools are useful for the assessment of disease activity and may predict structural progression,¹⁰ currently there is no consensus on the disease activity index that defines clinical remission. In addition, the available tools are associated with methodologic flaws that invalidate their universal application for the assessment of clinical remission.

Reduction of disease flare and slowing of structural progression as evident on MRI imaging, are integral to the definition of disease remission. However, currently, there is no universally accepted and validated definition of disease flare, and a suitable MRI scoring system and assessment of structural progression are unavailable.⁷ Furthermore, none of the available measures account for the presence of inflammation on imaging; the ASAS PR and the ASDAS do not take into consideration peripheral extra-articular manifestations such as enthesitis and uveitis. Assessment of C-reactive protein is excluded in the ASAS PR, while the ASDAS excludes assessment of function.

Axial spondyloarthritis is a complex disease with peripheral and axial manifestations. The focus has been on the appropriate definition of clinical remission and the suitability of the available tools to measure it. However, when patients’ perspectives are taken into consideration, it is evident that how remission is defined is influenced by a patients’ perception of their disease and their desired treatment outcome. As such, a less stringent definition of remission may be acceptable, such as prevention of further structural progression or minimal disease activity rather than the absence of clinical and laboratory evidence of significant inflammatory disease. In addition, given the cost of treatment, a patient may perceive remission as a reduction of pain and fatigue, in contrast to the physician’s perception of remission, which requires evidence of reduced structural progression.

The recommendation by the ASAS/EULAR guidelines⁹ for the inclusion nonpharmacologic intervention with the pharmacologic treatment of axSpA may further influence how remission is defined and measured. “Nonpharmacologic therapies are important and should also be considered as part of the treatment strategy for axSpA”, said Xenofon Baraliakos, MD, Department of Rheumatology, Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Germany, and lead author of the review. “[The] only issue is that many of these [nonpharmacologic strategies] do not really lead to remission,” Dr Baraliakos added. The impact of nonpharmacologic treatments in patients with axSpA has been evaluated in a systematic review, and while the studies included in the analysis were very heterogeneous, overall they confirmed that regular exercise could lead to small improvements in disease activity, function, and spinal mobility.¹¹

Based on the several variables that can influence the definition of remission, Baraliakos and colleagues have identified a number of questions that should be answered before remission can be incorporated into clinical practice as a treatment target. ⁷ These questions are related to how remission is defined, the optimal treatment strategy, and cost-benefit analysis. From a clinical practice perspective, given the several confounding variables, and especially taking patients’ perspective into consideration, “remission” should encompass a definition beyond the absence of clinical and laboratory evidence of significant inflammatory disease, and should include measures from appropriate assessment tools developed from well-designed clinical trials.

References

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