NSAIDs and Radiographic Progression in Ankylosing Spondylitis

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NSAIDs and Radiographic Progression in
Ankylosing Spondylitis

• By
• Abd El-Samad El-Hewala
• Professor of Rheumatology and Rehabilitation
• Faculty of Medicine - Zagazig University

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Background

• Non- steroidal anti-inflammatory drugs (NSAIDs)
  including coxibes, are recommended as first line
  drug treatment for ankylosing spondylitis
  patients with inflammatory back pain and
  stiffness

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Outlines

• Spondyloarthritis Variants
• Ankylosing Spondylitis
• Are NSAIDs Disease-Modifying Anti- rheumatic
  Drugs (DMARDs)?
• Biological Basis For NSAIDs Influencing Bone
  Formation
• Personalized management of AS.

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Spondyloarthritis

• Early recognition of spondyloarthritis (SpA)
  is challenging since the concept of SpA comprises
  a heterogeneous group of inflammatory
  arthropathies that share distinctive clinical,
  radiographic and genetic features. This group of
  arthritis include
• Ankylosing spondylitis
• Reactive arthritis (Reiter's syndrome)
• Psoriatic arthritis
• Enteropathic arthritis (Crohns, Ulcerative
  colitis)

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Features
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Dactylitis
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• Although many young patients with AS may be at
  lower risk of gastrointestinal and cardiac
  adverse events with NSAIDs therapy than older
  patients with other rheumatic diseases, patients
  and physicians alike continue to raise questions
  about the optimal role of these agents in AS

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• I - Are NSAIDs Disease-modifying anti-rheumatic
  Drugs
• ( DMARDs)?

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• Boersma (1976) in earlier study examined
  phenylbutazone in AS and concluded that this
  agent not only improved the symptoms, but also
  appeared to influence progression of new bone
  formation in the spine
• Boersma JW, Retardation of ossification of the
  lumber vertebral column in AS by mean of
  phenylbutazone.Scan Jrheumatol, 1976

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• Recently, Wanders et. al., 2005 found that the
  continuous use of celecoxib, in contrast with
  on-demand use, was also associated with less
  radiographic progression in AS.
• Wanders et. al. NSADs reduce radiographic
  progression in patients with ankylosing
  spondylitis a randomized clinical trial.
  Arthritis Rheumato. 2005

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• Recent data reported a reduced rate of
  progression of the modified Stokes Ankylosing
  Spondylitis Spinal Score (mSASSS) in patients who
  continue to take NSAIDs while being on anti- TNF
  for AS. This finding raise interest in the
  potential disease modifying effects of NSAIDs
• Haroon et. al., continuance of NSAIDs may
  reduce radiographic progression in AS patients on
  biologic therapy. Arthritis Rheum. 2011

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• The application of continuous NSAID therapy in
  AS patients with elevated acute phase reactants
  may lead to an improved benefit / risk ratio of
  these drugs.
• Young patients with AS may be at lower risk of
  gastrointestinal and cardiac adverse events with
  NSAID therapy than older patients with other
  rheumatic diseases.

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II- Biological Basis For NSAIDs Influencing Bone
Formation
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• NSAIDs reduce prostaglandin synthesis, and the
  issue of their effect on AS progression is very
  timely as recent genome- wide association
  studies in AS have shown an association of the
  gene prostaglandin E receptor 4 ( PTGER4) with AS
  .
• Thus bone desorption can be affected by PTGER4
  gene, and this effect may be modified by NSAIDs.
• Evans et. al, Nat. Genet 2011

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• Prostaglandins can also stimulate osteoblast
  formation, and this effect appears to depend on
  their concentration. Thus differences in local
  concentrations of prostaglandins could explain
  the paradoxical new bone formation and
  osteoprosis seen in AS.
• Ramirez-Yanez Arch Oral Biol 2012

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• III- Personalized Management of AS

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What is the symptomatic state of this patient at
presents?
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What is the likelihood of radiographic
progression in this patients?
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What are the risks of continuous NSAIDtreatment
in this patient?
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What treatment alternatives are availablefor
this patient?
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Conclusions

• The therapeutic management of AS has progressed
  considerably over the past 10 years with the
  development of TNF-a blockers.
• NSAIDs remain the reference drug class that must
  be proposed as a first-line treatment.
• Kroon F. et al Ann. Rheum. Dis. 2012

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Conclusions

• For the domains of pain, physical function and
  patients overall assessment, the effect size of
  both TNF-a blockers and NSAIDs is large or
  medium, while for the domain of mobility, it is
  small.
• Kroon F. et al Ann. Rheum. Dis. 2012

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