1. NSAIDs and Radiographic Progression in Ankylosing Spondylitis By Abd El-Samad El-Hewala Professor of Rheumatology and Rehabilitation Faculty of Medicine - Zagazig University

2. 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

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

4. 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)

6. Features

14. Dactylitis

18. 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

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

20.  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

21. continuous on-demand  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

22.  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

23.  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.

26. II- Biological Basis For NSAIDs Influencing Bone Formation

27.  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

28.  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

29. III- Personalized Management of AS

30. What is the symptomatic state of this patient at presents?

31. What is the likelihood of radiographic progression in this patients?

32. What are the risks of continuous NSAID treatment in this patient?

33. What treatment alternatives are available for this patient?

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

35. TNF- α blockers NSAIDs 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 Conclusions