asas berlin meeting - questionnaire results asas – recent achievements 1.general remarks...

ASAS Berlin Meeting - Questionnaire Results

ASAS – recent achievements

1. General remarks2. Improvement Criteria3. Anti-TNF Treatment recommendations

Prof.J.BraunRheumazentrum RuhrgebietHerneFree University BerlinGermany


SpA subtypes

1. Ankylosing spondylitis (AS)

2. Undifferentiated SpA

3. Psoriatic SpA

4. Reactive SpA

5. SpA associated with chronic inflammatory bowel diseases

AS

EULAR proposal for terminology: Spondyloarthritis (SpA)Francois R, Eulderink F, Bywaters EGL. Ann Rheum Dis 1995; 54:615-625

Outcome !


• Clinical Criteria– inflammatory back pain (Calin 1977)– reduced spinal mobility in 2 planes ( < 3 cm)– reduced thoracic excursion (< 3cm)

• Radiologic Criterium– sacroiliitis of > grade II bilat, > grade II unilat

van der Linden et al. A & R 1984

Modified New York Criteria 1984 for Diagnosis/Classification of

Ankylosing Spondylitis


• 2 major criteria – inflammatory back pain– asymmetric oligoarthritis of the lower limbs

• 7 minor criteria– enthesitis (heel)– alternating buttock pain– sacroiliitis (radiographic)– family history of SpA– psoriasis– inflammatory bowel disease– symptomatic preceding infection (urogenital, enteral)

Dougados M et al. A&R 1991

ESSG Criteria 1991 for Spondyloarthritis


• unequivocal SpA symptoms, but no definitive– Spondylitis ankylosans– Psoriatic arthritis– Reactive arthritis– Arthritis associated with CED

• covers– early cases– abortive forms– overlaps, transitions

• differentiation towards – AS sacroiliitis < grade II– ReA clinical picture, antibodies, PCR

• 30-50% development of AS

Undifferentiated Spondyloarthritis


• Diagnosis– 5 subgroups (AS, PSpA, uSpA, RSpA, SpAIBD)

• Outcome, Monitoring– Disease activity (BASDAI)– Pain (VAS, NRS scales)– Patient global assessment (VAS, NRS scales)– Inflammation (morning stiffness, CRP, ESR)– Localisation (axial, peripheral, organ manifestations)– Spinal mobility (BASMI)– Function (BASFI)– Damage (mod. SASSS, BASRI, MRI score)– Quality of life (SF-36, AS-Quol)

Assessments in Spondyloarthritides


Braun J et al. Rheum Dis Clin North Am 1998; 24: 697-735Brandt J et al. Arthritis Rheum 2000; 43: 1346-52

Ankylosing spondylitis - detection of spinal inflammation by MRI


Braun J, van der Heijde D. Best Pract Res Clin Rheumatol 2002 Sep;16(4): 573-604

Scoring active spinal inflammation in ankylosing spondylitis by ASspiMRI-a


36

57

55

-19

-28

-40

-30

-20

-10

0

10

20

30

40

50

60

70Post-Gad. STIR T1

%-c

ha

nge

Braun J et al., Arthritis Rheum 2003 April; 48: 1126

Relative changes of MRI scores on infliximab (n=9) or placebo (n=11) therapy


• Inflammatory back pain – (questionnaires, pain scales)

• Spinal mobility– BASMI, chest expansion, lat. Schober

• Joint counts – (44 J.C.)

• Enthesitis scores – (MASES, ..)

• Dactylitis

Organ involvement • anterior uveitis (n flares)

• psoriasis• colitis• other organ involvement

Assessments in Spondyloarthritides


20% Improvement:

1. Patient global

2. Pain

3. Function (BASFI)

4. Inflammation (last 2 questions of the BASDAI on morning stiffness)

(JJ Anderson, D van der Heijde, DT Felson, M Dougados. A&R 2001;)

Partial remission:

• improvement of at least 20% and absolute improvement of

at least 10 on a 0-100 scale in at least 3 of the following domains:

• absence of deterioration of at least 20% and absolute change of

at least 10 on a 0-100 scale in the potential remaining domain

• a value below 20 on a 0-100 scale in each of the 4 domains

and

ASAS working group criteria for improvement and remission in AS

ASAS Berlin Meeting - Questionnaire ResultsImprovement criteria for treatment with biologics in AS – a data driven analysis based on the RCT with Infliximab (n=69)

Improvement definition % improving in the placebo-treated

group

% improving in the infliximab-treated

group

2

20% change in any 5 of 6 2.9 67.7 31.9

20% change in any 4 of 5 (without CRP)

8.6 76.5 32.6

30% change in any 4 of 6 5.7 64.7 26.5

20% change in any 4 of 5 (incl. BASDAI instead of Morning stiffness)

5,7 67,6 28,6

Reference criteria 50% change of the BASDAI 8.6 58.8 19.6

40% change of the BASDAI 8.6 64.7 23.5

50% ASAS 5.7 52.9 18.7

40% ASAS 5.7 64.7 26.5

Domains: 1. Metrology (BASMI) 4. Patients global (VAS) 2. CRP 5. Function (BASFI) 3. Pain on VAS 6. Morning stiffness/BASDAI

ASAS Berlin Meeting - Questionnaire ResultsDevelopment of a consensus on anti-TNF Therapy in ankylosing spondylitis

• 1st Meeting in Berlin in January 2002• First Questionnaire Results• ASAS Delphi Exercise (M.Dougados)• ASAS Meeting Stockholm: decision• Preparation of 2nd Berlin Meeting • ASAS Delphi exercise • 2nd Meeting in Berlin in January 2003• Publication of two papers in Ann Rheum Dis 9/2003

• ASAS consensus• Results of Delphi exercise


First questionnaire

Full ASAS members participation : 61% (36/59)

Second questionnaire

Full ASAS members participation : 56% (33/59)

ASAS members participation


23%

29%

20%

23%

3% 3%

0%

5%

10%

15%

20%

25%

30%

0-10% 11 - 20% 21 - 30% 31 -50% 51-70% 71-100%

AS

AS

mem

ber

s es

tima

tion

Percentage of patients potentially candidate for biologics

Question 1


Do you consider that the sensitivity and specificity of the future practice guidelines for biologics in AS should be assessed ? (gold standard = rheumatologists’ opinion)

Yes : 89%

If yes, do you consider that sensitivity and specificity should be assessed before publishing the ASAS recommendations?

Yes : 52% No : 48%

Question 3


Should we go for strict guidelines (high thresholds) or for flexible guidelines (low thresholds)?

Strict : 40%

Flexible : 60%

Must the guidelines and proposed cut-offs always evidence based, or experts agreed, where evidence is lacking?

Strict EBM : 12%

EBM and/or Experts’ opinion: 88%

Question 1

Question 2


Topic 1

When can biologics initiation can be considered, in daily practice?


Do you agree with the separation into 3 categories : isolated axial involvement, peripheral arthritis, enthesitis?

Yes : 71% Disagreement was mainly because : • artificial separation• frequent association of the 3 categories, especially enthesitis with the 2

others “enthesitis should not be considered as a distinct entity”• does not take into account the “weight” of the different categories (one swollen

joint or one painful enthesis doesn't seem strong enough as convincing indication)

Question 4


Are the criteria selected by the Delphi exercise for axial involvement acceptable for you?

Yes : 75%

Question 5 (1/3)


5b. Chosen cut off 2 NSAIDs (Refractory to NSAIDs) 2– VAS 40 mm (Patient’s global assessment) 3– VAS 40 mm (Inflammatory pain) 3– BASFI 40 (Functional impairment ) 2– ESR > 28 (Laboratory parameters) 3– abnormal range CRP (Laboratory parameters) 3

Disagreement was because :

5a. Chosen variables– Refractory to NSAIDs 0– Patient’s global assessment 0– Inflammatory pain 0– Functional impairment 1– Laboratory parameters (ESR, CRP) 3

Number of ASAS members who selected the item

Question 5 (2/3)


Number of ASAS members who selected the item

5c. 3 of 4 rule– Biologics initiation can be based on patient derived variables only 5– Biologics initiation can be considered for patient without pain 3– Function is not relevant to consider biologics initiation 2– Pain is not relevant enough to consider biologics initiation 0– Patient’s global is not relevant enough 1– BASDAI is more relevant 3

Other propositions– Objective parameters needed 3– Lacking past history and severity of the disease 1– Should treat patients equally irrespective of ESR or CRP 1– 3 months duration NSAIDs period too long 1

Disagreement was because :

Question 5 (3/3)


Are the criteria selected by the Delphi exercise for enthesitis presentation acceptable for you?

Yes : 69%

Question 7 (1/3)


How do you rate the view considering 3 groups of variables (patient derived variables, physician derived variables,

technical) compared to the results of the Delphi exercise?

• Much better 11%• Somewhat better 30%

• Similar 33%

• Somewhat worse 22%• Much worse 0%

• I don’t know 3%

41%

22%

Question 8


Concerning the initiation of biologics in AS, which of the following do you feel should be considered?

Question 4

63%

3%

13%

22%

0% 20% 40% 60% 80% 100%

Patient's assessmentalone

Patient's assessment +Objective assessment

Patient's assessment +Physician's assessment

All three


Concerning the objective assessments, what is your opinion concerning the definition of an active disease?

Question 10 (1/3)

91%

73%

55%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

“Elevated CRP” Positive spinal MRI Rapid radiographicprogression


94%

75%

61%

53%

44%

36%

33%

33%

72%

81%

11%

89%

53%

42%

72%

31%

19%

75%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Patient global VAS

Pain VAS

Night Pain VAS

Chest expansion

Modified Schöber

Occiput-wall dist

Lat Spinal flexion

BASMI

Morning stiffness

BASFI

Dougados FI

Swollen joint

Enthesitis score

Fatigue VAS

ESR

CRP

X-Rays spine

X- Rays pelvis

Sp

ina

l mo

bili

tyF

un

ctio

nA

cute

ph

ase

re

act

an

ts

Question 12 (1/2)Variables to collect in order to evaluate biologics efficacy

ASAS Berlin Meeting - Questionnaire ResultsInternational ASAS consensus statement for the clinical use of anti-TNF-treatment

in patients with Ankylosing Spondylitis in daily practice

International ASAS consensus statement for the clinical use of anti-TNF-treatment

in patients with Ankylosing Spondylitis in daily practice

Jürgen Braun, Thao Pham, Jochen Sieper, John Davis, Sjef van der Linden, Maxime Dougados and Désirée

van der Heijde for the ASAS Working Group

Berlin, Herne, Marseille, San Francisco, Paris, Maastricht


21. Heijde van der D, NL*22. Horst v.d.-Bruinsma I, NL23. Khan MA, USA 24. Kirazli J, Turkey25. Kuipers J, Germany26. Landewé R, NL27. Leirisalo-Repo M, Finland28. Linden v. d. S, NL *29. Linssen A., NL30. Listing J, Germany31. Maetzel A, Canada32. Maksymowych W, Canada33. Mielants H, Belgium34. Olivieri I., Italy35. Peloso P, USA36. Pham T, France37. Reveille J, USA 38. Riel van, NL39. Rudwaleit M, Germany40. Russell A S, Canada

41. Salvarani, C., Italy42. Sieper J., Germany *43. Stone M A, Canada44. Sturrock R, UK45. Yu, D, USA46. Zeidler H, Germany * Steering Committee Members of ASAS

1. Adebajo A O, UK2. Amor B, France3. Boers M, NL4. Boonen A, NL5. Bosch van den, F, Belgium6. Brandt J, Germany7. Braun J, Germany *8. Burgos Vargas R, Mexico9. Calin A, UK10. Clegg D, USA11. Collantes Estevez E, Spain12. Darmawan J, Indonesia13. Davis J, USA *14. Dougados M, France *15. Dijkmans B A C, NL16. Edmonds J, Australia17. Emery P, UK18. Feltelius N, Sweden19. Géher P, Hungary20. Guillemin F, France

List of ASAS members/ participants/questionnaire co-workers


• Introduction of anti-TNF agents has led to new therapeutic opportunities in the spondyloarthritides

• Efficacy of infliximab and etanercept in AS

• Approval of infliximab and etanercept for AS

• Uncertainty regarding the optimal use and potential side effects on anti-TNF agents

• Considerable costs of anti -TNF therapy

Why are guidelines for the use of anti-TNF treatment in AS needed?


• Review of the current literature

• Expert opinion

• Delphi exercise

• Consensus meeting of the international assessment in AS (ASAS) working group

Methodology employed to develop the guidelines


• What patients are appropriate candidates to consider for anti-TNF therapy ?

• How should response to anti-TNF therapy be measured ?

• When should anti-TNF therapy be continued and discontinued ?

Questions concerning the use of anti-TNF therapy in AS


• Persistence of active disease

• Threat of severe disease (damage)

• Likelihood of response to therapy

What patients are candidates to consider for anti-TNF

therapy?


• Initiation

• Monitoring• Discontinuation

ASAS Meeting in Berlin January 2003Braun J et al. Ann Rheum Dis 9/2003

1.1. DiagnosisDiagnosis

2.2. Disease activityDisease activity

3.3. Failure of conventional TreatmentFailure of conventional Treatment

4.4. Absence of contraindicationsAbsence of contraindications

5.5. MonitoringMonitoring

6.6. DiscontinuationDiscontinuation

International consensus on anti-TNF therapy in ankylosing spondylitis


• Patients ‘normally’ fulfilling the modified New York Criteria for definitive AS (1984 van der Linden et al.)

– Radiological criterion• Sacroiliitis, grade II bilaterally

or grade III to IV unilaterally

1. Diagnosis of ankylosing spondylitis


– Clinical criteria (1 out of the following 3)• Low back pain and stiffness for more than 3 months

that improves with exercise but is not relieved by rest• Limitation of motion of the lumbar spine in both the

sagittal and frontal planes• Limitation of chest expansion relative to normal

values correlated for age and sex

1. Diagnosis of ankylosing spondylitis


I. active disease for at least 4 weeks II. BASDAI 4 (0-10) and an expert* opinion**

* The expert is a physician, usually a rheumatologist, with expertise in inflammatory back pain and the use of biologics. The expert should be locally defined.

** An expert opinion is comprised of both clinical features (history and examination) and either serum acute phase reactant levels or imaging results, such as radiographs demonstrating rapid progression or MRI scans indicating inflammation.

2. Disease activity before anti-TNF therapy


• Different for patients with predominantly

– Axial disease

– Peripheral disease

– Entheseal disease

3. Treatment failure before anti-TNF therapy


• All patients must have had adequate

therapeutic trials of at least 2 NSAIDs.

• An adequate therapeutic trial is defined as :

– Treatment for at least 3 months at maximal

recommended or tolerated anti-inflammatory

dose unless contraindicated

– Treatment for < 3 months where treatment was

withdrawn because of intolerance, toxicity, or

contraindications.



• Patients with symptomatic peripheral arthritis

(normally having or failing local steroid injection for

those with oligoarticular involvement) must have had

adequate therapeutic trial of both NSAIDs and

salazopyrine*

• Salazopyrine: – Treatment for at least 4 months at standard target dose or maximally

tolerated dose unless contraindicated or not tolerated.

– Treatment for less than 4 months, where treatment was withdrawn

because of intolerance or toxicity or contraindicated.



• Patients with symptomatic enthesitis must have

had an adequate therapeutic trial of at least two

local steroid injections unless contraindicated.



• active infection• patients at high risk of infection including:

– chronic leg ulcer– previous tuberculosis (note: please follow local

recommendations for prevention or treatment)– septic arthritis of a native joint within the last

12 months– sepsis of a prosthetic joint within the last 12 months,

or indefinitely if the joint remains in situ

– persistent or recurrent chest infections

– Indwelling urinary catheter

4. Contraindications for anti-TNF therapy


• women who are pregnant or breastfeeding; – effective contraception must be practiced

• history of Lupus or Multiple Sclerosis

• malignancy or pre-malignancy states excluding – basal cell carcinoma

– malignancies diagnosed and treated more than 10 years previously (where the probability of total cure is very high)

4. Contraindications for anti-TNF4. Contraindications for anti-TNF therapy therapy4. Contraindications for anti-TNF4. Contraindications for anti-TNF therapy therapy


• BASDAI

• ASAS core set

5. Monitoring of anti-TNF therapy


• Physical function (BASFI or Dougados functional index)• Pain (VAS, last week, spine at night, due to AS and VAS,

last week, spine due to AS)• Spinal mobility (chest expansion and modified Schober and

occiput to wall distance and lateral lumbar flexion)• Patient’s global assessment (VAS, last week)• Stiffness (duration of morning stiffness, spine, last week)• Peripheral joints and entheses (number of swollen joints

[44 joints count], enthesitis score such as developed in Maastricht, Berlin or San Francisco)

• Acute phase reactants (ESR or CRP)• Fatigue (VAS)

van der Heijde et al. J Rheumatol 1997

ASAS core set of assessments for daily practice


• < 50% relative change or absolute

change of 20 mm of BASDAI and

Expert Opinion : Continuation yes/no

• after 6 to 12 weeks of treatment

6. Discontinuation of anti-TNF therapy


• Implementation in clinical practice• Regular update (2005)

• Recommendations will be published in the Annals of Rheumatic Diseases and become available on the website of the ARD and ASAS

• (publication of U.S.- specific Comments)

Further development


Personal proposal:

link PsA working group to ASAS

Future:

Assessments in SpA working group ?

asas berlin meeting - questionnaire results asas – recent achievements 1.general remarks...

Documents

mri slide

spondyloarthritides

reactive spa

psoriatic spa

undifferentiated spa

arthritis rheum

major criteria inflammatory

improvement criteria