1. Ankylosing spondylitis
Ankylosing spondylitis can impose significant physical limitations on the patient
It affect their ability to work and reducing quality of life
The onset being early (third decade) which increases the lifetime impact of the disease

2. Ankylosing spondylitis
Delay in diagnosis
Recent survey of 1614 patients with AS illustrate the protracted delay between onset and Diagnosis
Average of 8.9 years mean delay of making Dx.
In women the mean delay 9.8 vs 8.4 in Males (probably due to misconception that only men are affected)

3. Ankylosing spondylitis
Relative sensitivity of detecting active Sacroilliitis :
MRI
Plain Radiography
Quantitative Scintigraphy
MRI %
Plain radiography 19%
QS %
J Rheumatol 1996;

4. Ankylosing spondylitis
Only 50-70% of AS patients with active disease exhibit biological markers of inflammation with elevated ESR and CRP
Relative late appearance of radiographic sacroiliitis , by up to several years after first symptoms

5. Ankylosing spondylitis
Symptoms early in the disease are due to inflammation
Symptoms later in the disease are caused by a mixture of inflammation , structural spinal damage and secondary damage to soft tissue such as muscles and ligaments.

6. Ankylosing Spondylitis
Predictive factors for long term outcome:
-Hip arthritis is the strongest predictive factor being associated with 23-fold increase in the risk of severe arthritis
Other factors:
Age-onset before 16
High ESR
Unresponsive to NSAID
Limitation of lumbar spinal movement

7. Ankylosing spondylitis
About 60-75% of patients with AS show good to very good response to full dose NSAIDs in 48 hours , in contrast with only 15% of patients with mechanical back pain.
Recent study has shown that patients with AS treated continuously over two years with a daily dose of NSAIds has less radiological progression compare to those who took NSAIDs on demand
Arth Rheum 2005;

8. Ankylosing spondylitis
20-50% of AS patients still have active disease despite treatment with NSAID.
For those patients , Anti-TNF have meant
a breakthrough in treatment

9. Ankylosing spondylitis
-MRI follow up studies during treatment with etanrcept and infliximab have shown that acute inflammatory lesions in the spine and sacroiliac joints can be effectively suppressed , bony destruction and proliferation can be prevented

11. Etanercept in AS Sustained durability and tolerability for 96 weeks
Etanercept in AS Sustained durability and tolerability for 96 weeks. A&R :
-277 AS patients who were enrolled in RCT
(257 continued open labeled Etanrcept.
AS patients continuing Etanrcept Rx had sustained response for almost 2 years
Improvement is symptoms , signs and spinal mobility
None of the most serious safety concerns :TB, drug induced lupus, MS or lymphoma were reported .

12. Outcome in Active AS, Clinical and MRI data , 2-years A&R December 2005
26 patients with active AS treated with etanercept 25mg twice weekly
Conclusion : The clinical efficacy and safety of etanercept in patients with active AS without simultanous administration of DMARDs or steroids over 2 years of continuous treatment is confirmed
Spinal inflammation as depicted by MRI decreased significantly.

13. Ankylosing Spondylitis
ASAS/EULAR recommendations for
Management of AS
22 expert participants:
Ten Key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus.

14. Ankylosing Spondylitis
1- Treatment of AS should be tailored according to:
- Current Manifestations of the disease
-Level of current symptoms, clinical findings and prognostic indicators
-General clinical status
-Wishes and expectation of the patient

15. Ankylosing Spondylitis
2-Disease Monitoring:
-patient history
-clinical parameters
-laboratory tests
-Imaging
All according to clinical presentations and ASAS core set
Frequency of monitoring should be decided on symptoms, severity, and drug treatment

16. Ankylosing Spondylitis
3-Optimum therapy of AS requires pharmacological and non-pharmacological
treatment

17. Ankylosing Spondylitis
4-Non-pharmacological treatment of AS :
-Patient education
-regular exercises
-physical therapy
-Patients associations and self help groups may be useful.

18. Ankylosing spondylitis
5- NSAIDs are recommended as first line therapy for treatment of AS with pain and stiffness.
In those with increased GI risk , selective
COX2 inhibitors could be used.

19. Ankylosing spondylitis
6- Analgesics may be used for pain in whom NSAID are insufficient, contraindicated and or poorly controlled.

20. Ankylosing spondylitis
7- Corticosteroids injections directed to the local site of inflammation may be considered.
The use of systemic steroids for axial disease is not supported by evidence.

21. Ankylosing spondylitis
8-There is no evidence for the efficacy of DMARDs including SSZ and MTTX for the axial manifestations .
SSZ may be considered in patients with AS and peripheral arthritis.

22. Ankylosing spondylitis
9-Anti-TNF Rx should be given to patients with persistently high disease activity despite conventional treatment
There is no evidence to support the obligatory use of DMARDs before or concomitant with anti-TNF treatment in patients with axial disease

23. Ankylosing spondylitis
10-Total hip arthroplasty should be considered in patients with refractory pain and disability and radiographic evidence of structural damage.
Spinal surgery-for example corrective osteotomy and stabilization procedure may be value in selected cases.

24. Ankylosing spondylitis
First International ASAS consensus statements for the use of Anti-TNF agents in patients with ankylosing spondylitis
Published online ARD August 2005
Guidelines for the use on Anti-TNF in AS

25. Ankylosing spondylitis
-Anti-TNF therapy is considered as a major advances (breakthrough) in the treatment of AS patients
There is a need to identify
i-patients with active disease
ii-Patients with threatening functional disability
iii-patients who may have most benefits from Rx.

26. Ankylosing spondylitis
Etanrcept 25mg biweekly and infliximab 5mg/kg every 6-8weeks are approved in US and Europe for the treatment of signs and symptoms of patients with active AS
Adalimumab is not yet approved for AS
( US and EUROPE)

27. Ankylosing spondylitis
Only patients with active disease should be considered for treatment with antiTNF agents
Active disease as indicated by both
1- BASDAI score of =or>4 and
2- physician global assessment of =or>2
on a Likert Scale (1=mild,2=moderate, 3=severe , 4=very severe)
should be present to warrant anti-TNF therapy

28. Ankylosing spondylitis
Failure to respond to at least 2 NSAIDs , each NSAID should have been used for at least 3 months at maximum dose
Failure treatment of at least one DMARD for peripheral arthritis (SSZ or MTX)

29. Ankylosing spondylitis
Assessment of response to Rx is recommended after 6-8 weeks.
Improvement Criteria :
Improvement in BASDAI of=or > 2 in BASDIA score and physician global assessment of =or>1

30. Ankylosing spondylitis
Discontinuation of Anti-TNF :
If the response criteria are not met within 6-8 weeks , it is recommended to D/c the anti-TNF agents
The use of other anti-TNF may be considered.

31. Ankylosing spondylitis
There is no available data that active MRI and high CRP are required to support therapy with anti-TNF in individual patient

32. Ankylosing spondylitis
Conclusion:
AS can and has to be diagnosed earlier than is being done at present even before radiological changes are evident
Therapies with NSAIDs and TNF blockers are most effective for the signs ,symptoms that are caused by inflammation.

33. Ankylosing Spondylitis
The disappearance of inflammation in the spine and sacroiliac joints during treatment, as detected by MRI is a demonstration of great efficacy of TNF blockers and also suggests that structural damage may also be prevented
Ann Rheum Dis nline

34. Ankylosing Spondylitis
Whether and how these new treatments also have the potential to induce long term remission if given early enough has to be shown in the future.
Ann Rheum Dis nline