NSAIDs and Radiographic Progression

in Ankylosing Spondylitis

By

Abd El-Samad El-Hewala Professor of Rheumatology and Rehabilitation

Faculty of Medicine - Zagazig University

BackgroundBackground

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

OutlinesOutlinesSpondyloarthritis VariantsAnkylosing SpondylitisAre NSAIDs Disease-Modifying

Anti- rheumatic Drugs (DMARDs)?Biological Basis For NSAIDs

Influencing Bone FormationPersonalized management of AS.

SpondyloarthritisSpondyloarthritis

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)

FeaturesFeatures

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 continuouscontinuous use of celecoxib, in contrast with on-on-demanddemand 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?

ConclusionsConclusionsThe therapeutic management of AS

has progressed considerably over the past 10 years with the development of TNF-α blockers.

NSAIDs NSAIDs remain the reference drug class that must be proposed as a as a first-line first-line treatment.

Kroon F. et al Ann. Rheum. Dis. 2012

For the domains of pain, physical function and patient’s overall assessment, the effect size of both TNF-α blockers TNF-α blockers and NSAIDsNSAIDs is large or medium, while for the domain of mobility, it is small.

Kroon F. et al Ann. Rheum. Dis. 2012

ConclusionsConclusions