ankylosing spondylitis ankylosing spondylitis can impose significant physical limitations on the...

Ankylosing spondylitisAnkylosing spondylitis

Ankylosing spondylitis Ankylosing spondylitis can impose significant can impose significant physical limitations on physical limitations on the patientthe patient

It affect their ability to It affect their ability to work and reducing work and reducing quality of lifequality of life

The onset being early The onset being early (third decade) which (third decade) which increases the lifetime increases the lifetime impact of the diseaseimpact of the disease


Delay in diagnosisDelay in diagnosis Recent survey of 1614 patients with AS Recent survey of 1614 patients with AS

illustrate the protracted delay between illustrate the protracted delay between onset and Diagnosisonset and Diagnosis

Average of 8.9 years mean delay of Average of 8.9 years mean delay of making Dx.making Dx.

In women the mean delay 9.8In women the mean delay 9.8 vs 8.4 in vs 8.4 in MalesMales (probably due to misconception (probably due to misconception thatthat only men are affected)only men are affected)

Ankylosing spondylitisAnkylosing spondylitis Relative sensitivity of Relative sensitivity of

detecting active Sacroilliitis :detecting active Sacroilliitis :

MRIMRI Plain RadiographyPlain Radiography Quantitative Quantitative

ScintigraphyScintigraphy MRI 95%MRI 95% Plain radiography 19%Plain radiography 19% QS 48%QS 48%J Rheumatol 1996;23-2107-15J Rheumatol 1996;23-2107-15


Only 50-70% of AS patients with active Only 50-70% of AS patients with active disease exhibit biological markers of disease exhibit biological markers of inflammation with elevated ESR and inflammation with elevated ESR and CRPCRP

Relative late appearance of Relative late appearance of radiographic sacroiliitis , by up to radiographic sacroiliitis , by up to several years after first symptomsseveral years after first symptoms


Symptoms early in the disease are Symptoms early in the disease are due to inflammationdue to inflammation

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

Ankylosing SpondylitisAnkylosing Spondylitis

Predictive factors for long term outcome:Predictive factors for long term outcome:

-Hip arthritis is the strongest predictive -Hip arthritis is the strongest predictive factor being associated with 23-fold factor being associated with 23-fold increase in the risk of severe arthritisincrease in the risk of severe arthritis

Other factors:Other factors:- Age-onset before 16Age-onset before 16- High ESRHigh ESR- Unresponsive to NSAIDUnresponsive to NSAID- Limitation of lumbar spinal movementLimitation of lumbar spinal movement


About 60-75% of patients with AS show good to About 60-75% of patients with AS show good to very good response to full dose NSAIDs in 48 very good response to full dose NSAIDs in 48 hours , in contrast with only 15% of patients hours , in contrast with only 15% of patients with mechanical back pain.with mechanical back pain.

Recent study has shown that patients with AS Recent study has shown that patients with AS treated continuously over two years with a treated continuously over two years with a daily dose of NSAIds has less radiological daily dose of NSAIds has less radiological progression compare to those who took NSAIDs progression compare to those who took NSAIDs on demandon demand

Arth Rheum 2005;52-1756-65Arth Rheum 2005;52-1756-65


20-50% of AS patients still have active 20-50% of AS patients still have active disease despite treatment with NSAID.disease despite treatment with NSAID.

For those patients , Anti-TNF have For those patients , Anti-TNF have meant meant

a breakthrough in treatmenta breakthrough in treatment


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

Etanercept in AS Etanercept in AS Sustained durability and tolerability for 96 Sustained durability and tolerability for 96

weeks.weeks.A&R 2005-64:1557-62A&R 2005-64:1557-62

-277 AS patients who were enrolled in RCT -277 AS patients who were enrolled in RCT (257 continued open labeled Etanrcept.(257 continued open labeled Etanrcept.AS patients continuing Etanrcept Rx had AS patients continuing Etanrcept Rx had

sustained response for almost 2 yearssustained response for almost 2 years Improvement is symptoms , signs and Improvement is symptoms , signs and

spinal mobilityspinal mobility None of the most serious safety None of the most serious safety

concerns :TB, drug induced lupus, MS or concerns :TB, drug induced lupus, MS or lymphoma were reported .lymphoma were reported .

Outcome in Active AS, Clinical Outcome in Active AS, Clinical and MRI data , 2-years and MRI data , 2-years A&R December 2005A&R December 2005

26 patients with active AS treated with 26 patients with active AS treated with etanercept 25mg twice weekly etanercept 25mg twice weekly

Conclusion : The clinical efficacy and Conclusion : The clinical efficacy and safety of etanercept in patients with active safety of etanercept in patients with active AS without simultanous administration of AS without simultanous administration of DMARDs or steroids over 2 years of DMARDs or steroids over 2 years of continuous treatment is confirmed continuous treatment is confirmed

Spinal inflammation as depicted by MRI Spinal inflammation as depicted by MRI decreased significantly. decreased significantly.


ASAS/EULAR recommendations for ASAS/EULAR recommendations for

Management of ASManagement of AS

22 expert participants: 22 expert participants:

Ten Key recommendations for the Ten Key recommendations for the treatment of AS were developed and treatment of AS were developed and assessed using a combination of assessed using a combination of research based evidence and expert research based evidence and expert consensus.consensus.


11- Treatment of AS should be tailored - Treatment of AS should be tailored according to:according to:

- Current Manifestations of the disease- Current Manifestations of the disease

-Level of current symptoms, clinical -Level of current symptoms, clinical findings and prognostic indicatorsfindings and prognostic indicators

-General clinical status-General clinical status

-Wishes and expectation of the patient-Wishes and expectation of the patient


2-Disease Monitoring:2-Disease Monitoring:-patient history-patient history-clinical parameters-clinical parameters-laboratory tests-laboratory tests-Imaging-ImagingAll according to clinical presentations and All according to clinical presentations and

ASAS core setASAS core setFrequency of monitoring should be decided Frequency of monitoring should be decided

on symptoms, severity, and drug treatmenton symptoms, severity, and drug treatment


3-Optimum therapy of AS requires 3-Optimum therapy of AS requires pharmacological and non-pharmacological and non-pharmacological pharmacological

treatmenttreatment


4-Non-pharmacological treatment of 4-Non-pharmacological treatment of AS :AS :

-Patient education-Patient education

-regular exercises-regular exercises

-physical therapy-physical therapy

-Patients associations and self help -Patients associations and self help groups may be useful.groups may be useful.


5- NSAIDs are recommended as first 5- NSAIDs are recommended as first line therapy for treatment of AS with line therapy for treatment of AS with pain and stiffness.pain and stiffness.

In those with increased GI risk , In those with increased GI risk , selectiveselective

COX2 inhibitors could be used. COX2 inhibitors could be used.


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


7- Corticosteroids injections directed 7- Corticosteroids injections directed to the local site of inflammation may to the local site of inflammation may be considered.be considered.

The use of systemic steroids for axial The use of systemic steroids for axial disease is not supported by disease is not supported by evidence.evidence.


8-There is no evidence for the 8-There is no evidence for the efficacy of DMARDs including SSZ efficacy of DMARDs including SSZ and MTTX for the axial and MTTX for the axial manifestations .manifestations .

SSZ may be considered in patients SSZ may be considered in patients with AS and peripheral arthritis.with AS and peripheral arthritis.


99-Anti-TNF Rx should be given to -Anti-TNF Rx should be given to patients with persistently high disease patients with persistently high disease activity despite conventional activity despite conventional treatmenttreatment

There is no evidence to support the There is no evidence to support the obligatory use of DMARDs before or obligatory use of DMARDs before or concomitant with anti-TNF treatment concomitant with anti-TNF treatment in patients with axial disease in patients with axial disease


10-Total hip arthroplasty should be 10-Total hip arthroplasty should be considered in patients with refractory considered in patients with refractory pain and disability and radiographic pain and disability and radiographic evidence ofevidence of structural damage. structural damage.

Spinal surgery-for example corrective Spinal surgery-for example corrective osteotomy and stabilization procedure osteotomy and stabilization procedure may be value in selected cases.may be value in selected cases.


First International ASAS First International ASAS consensus statements for the consensus statements for the use of Anti-TNF agents in use of Anti-TNF agents in patients with ankylosing patients with ankylosing spondylitisspondylitis

Published online ARD August 2005Published online ARD August 2005 Guidelines for the use on Anti-TNF in ASGuidelines for the use on Anti-TNF in AS


-Anti-TNF therapy is considered as a major -Anti-TNF therapy is considered as a major advances (breakthrough) in the treatment of advances (breakthrough) in the treatment of AS patientsAS patients

There is a need to identifyThere is a need to identify i-patients with active diseasei-patients with active disease ii-Patients with threatening functional disabilityii-Patients with threatening functional disability iii-patients who may have most benefits from iii-patients who may have most benefits from

Rx.Rx.


Etanrcept 25mg biweekly and Etanrcept 25mg biweekly and infliximab 5mg/kg every 6-8weeks infliximab 5mg/kg every 6-8weeks are approved in US and Europe for are approved in US and Europe for the treatment of signs and symptoms the treatment of signs and symptoms of patients with active ASof patients with active AS

Adalimumab is not yet approved for Adalimumab is not yet approved for ASAS

( US and EUROPE)( US and EUROPE)


Only patients with active disease should be Only patients with active disease should be considered for treatment with antiTNF considered for treatment with antiTNF agentsagents

Active disease as indicated by bothActive disease as indicated by both 1- BASDAI score of =or>4 and 1- BASDAI score of =or>4 and 2- physician global assessment of =or>2 2- physician global assessment of =or>2 on a Likert Scale (1=mild,2=moderate, on a Likert Scale (1=mild,2=moderate,

3=severe , 4=very severe) 3=severe , 4=very severe) should be present to warrant anti-TNF therapyshould be present to warrant anti-TNF therapy


Failure to respond to at least 2 Failure to respond to at least 2 NSAIDs , each NSAID should have NSAIDs , each NSAID should have been used for at least 3 months at been used for at least 3 months at maximum dosemaximum dose

Failure treatment of at least one Failure treatment of at least one DMARD for peripheral arthritis (SSZ DMARD for peripheral arthritis (SSZ or MTX)or MTX)


Assessment of response to Rx is Assessment of response to Rx is recommended after 6-8 weeks.recommended after 6-8 weeks.

Improvement Criteria :Improvement Criteria :

Improvement in BASDAI of=or > 2 Improvement in BASDAI of=or > 2 in BASDIA score and physician in BASDIA score and physician global assessment of =or>1global assessment of =or>1


Discontinuation of Anti-TNF :Discontinuation of Anti-TNF : If the response criteria are not met If the response criteria are not met

within 6-8 weeks , it is within 6-8 weeks , it is recommended to D/c the anti-TNF recommended to D/c the anti-TNF agents agents

The use of other anti-TNF may be The use of other anti-TNF may be considered.considered.


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


Conclusion:Conclusion: AS can and has to be diagnosed earlier AS can and has to be diagnosed earlier

than is being done at present even than is being done at present even before radiological changes are evidentbefore radiological changes are evident

Therapies with NSAIDs and TNF Therapies with NSAIDs and TNF blockers are most effective for the blockers are most effective for the signs ,symptoms that are caused by signs ,symptoms that are caused by inflammation.inflammation.


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

Ann Rheum Dis 2005-0nline Ann Rheum Dis 2005-0nline


Whether and how these new Whether and how these new treatments also have the potential to treatments also have the potential to induce long term remission if given induce long term remission if given early enough has to be shown in the early enough has to be shown in the future. future.

Ann Rheum Dis 2005-0nline Ann Rheum Dis 2005-0nline

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