NSAIDs and Radiographic
Progression
in
Ankylosing Spondylitis
By
Abd El-Samad El-Hewala
Professor of Rheumatology and Rehabilitation
Faculty of Medicine - Zagazig University
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
Outlines
Spondyloarthritis Variants
 Ankylosing Spondylitis
 Are NSAIDs Disease-Modifying
Anti- rheumatic Drugs (DMARDs)?
 Biological Basis For NSAIDs Influencing Bone
Formation
 Personalized management of AS.

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)
Features
Dactylitis

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
I - Are NSAIDs Disease-modifying
anti-rheumatic Drugs
( DMARDs)?
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
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
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
 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.
II- Biological Basis For NSAIDs
Influencing Bone Formation
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
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
III- Personalized Management
of AS
What is the symptomatic state of
this patient at presents?
What is the likelihood of
radiographic progression in this
patients?
What are the risks of continuous
NSAID
treatment in this patient?
What treatment alternatives are
available
for this patient?
Conclusions
The
therapeutic management of AS has
progressed considerably over the past 10
years with the development of TNF-α
blockers.
NSAIDs remain the reference drug class that
must be proposed as a first-line treatment.
Kroon F. et al Ann. Rheum. Dis. 2012
Conclusions

For the domains of pain, physical function
and patient’s overall assessment, the effect
size of both TNF-α blockers and NSAIDs is
large or medium, while for the domain of
mobility, it is small.
Kroon F. et al Ann. Rheum. Dis. 2012