Therapeutic Controversies in Spondyloarthritis: Nonsteroidal Anti-Inflammatory Drugs
Introduction
Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered a first-line therapy in patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS).1 Beyond NSAIDs, only tumor necrosis factor α (TNF-α) blockers are currently available and effective for treating axial signs and symptoms of patients with active axSpA.1, 2 In contrast to rheumatoid arthritis, for example, disease-modifying antirheumatic drugs and corticosteroids play only a minor role in the management of axSpA, and only in the case of peripheral joint involvement.3, 4 In the joint ASAS (Assessment of SpondyloArthritis international Society) and EULAR (European League Against Rheumatism) recommendations for the management of axSpA, continuous treatment with NSAIDs is preferred for patients with persistently active symptomatic disease.1 Continuous treatment with NSAIDs, however, raises safety issues. In a survey on the application of the ASAS/EULAR recommendations, 38% of European rheumatologists mentioned safety concerns as the main barrier for not using NSAIDs more consistently in patients with AS.5
This article discusses the current role of NSAIDs in axSpA treatment, including the risks and benefits of NSAID use and current trends for more individualized treatment strategies.
Section snippets
Clinical efficacy of NSAIDs
So far, clinical trials with NSAIDs have only been performed in patients with established AS. However, based mainly on clinical experience, NSAIDs can be expected also to be highly effective in patients with nonradiographic axSpA (nr-axSpA), or those with axSpA who did not develop (yet) radiographic sacroiliitis. Thus, patients with nr-axSpA should be treated with NSAIDs similarly to those with AS.6 Furthermore, NSAIDs also play an important role in the management of patients with predominant
Influence of NSAIDs on local and systemic inflammation in axSpA
The high clinical efficacy of NSAIDs in axSpA indicates that their anti-inflammatory properties are more relevant for reducing pain and stiffness in this disease than their analgesic capacity only. However, the data indicating effective control of systemic and local inflammation with NSAIDs are limited.
C-reactive protein (CRP) is a sensitive marker of systemic inflammation, and an elevated level of CRP could be found in approximately 50% of the patients with axSpA.16 Elevated serum CRP level
Influence of NSAIDs on radiographic spinal progression in axSpA/AS
The high efficacy of NSAIDs in reducing clinical symptoms, and to some extent reducing signs of systemic inflammation (CRP), raises the question whether NSAIDs are only symptomatically effective or whether they might have an additional effect on the long-term outcome of axSpA/AS.
Radiographic spinal progression, which is mostly related to the process of new bone formation, or the development of syndesmophytes leading to the bony ankylosis of the spine (Fig. 2), seems to be an important
Safety of NSAIDs and risk/benefit estimation of NSAID therapy in SpA
Serious safety concerns are always raised when long-term NSAID treatment is discussed. Several safety aspects are related to NSAID treatment, such as gastrointestinal, cardiovascular, renal, hepatic, and allergic reactions. The most common and clinically relevant are the first 2, which are discussed further.
Gastrointestinal toxicity is a well-known adverse effect during NSAID treatment, which is related mainly to inhibition of prostaglandin synthesis in the gastric mucosa. The most important
Summary
NSAIDs are highly effective in reducing symptoms of axSpA, including AS, and therefore considered a first-line therapy in this disease. NSAIDs might have an impact on radiographic spinal progression in AS if administered continuously. The greatest effect on radiographic progression is expected in patients with syndesmophytes who have an elevated CRP. However, the primary goal of treatment in patients with AS should be to eliminate symptoms, whereas retardation of radiographic progression
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Disclosures: Denis Poddubnyy has received consultancy and speaking fees from Merck; Désirée van der Heijde has received consultancy fees from Merck and Pfizer.