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ASAS – recent achievements

ASAS – recent achievements. General remarks Improvement Criteria Anti-TNF Treatment recommendations. Prof.J.Braun Rheumazentrum Ruhrgebiet Herne Free University Berlin Germany.

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ASAS – recent achievements

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  1. ASAS – recent achievements • General remarks • Improvement Criteria • Anti-TNF Treatment recommendations Prof.J.Braun Rheumazentrum Ruhrgebiet Herne Free University Berlin Germany

  2. EULAR proposal for terminology:Spondyloarthritis (SpA)Francois R, Eulderink F, Bywaters EGL. Ann Rheum Dis 1995; 54:615-625 SpA subtypes • Ankylosing spondylitis (AS) • Undifferentiated SpA • Psoriatic SpA • Reactive SpA • SpA associated with chronic inflammatory bowel diseases Outcome ! AS

  3. Modified New York Criteria 1984 for Diagnosis/Classification of Ankylosing Spondylitis • 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

  4. ESSG Criteria 1991 for Spondyloarthritis Dougados M et al. A&R 1991 • 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)

  5. Undifferentiated 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

  6. Assessments in Spondyloarthritides • 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)

  7. Ankylosing spondylitis - detection of spinal inflammation by MRI Braun J et al. Rheum Dis Clin North Am 1998; 24: 697-735 Brandt J et al. Arthritis Rheum 2000; 43: 1346-52

  8. Scoring active spinal inflammation in ankylosing spondylitis by ASspiMRI-a Braun J, van der Heijde D. Best Pract Res Clin Rheumatol 2002 Sep;16(4): 573-604

  9. Relative changes of MRI scores on infliximab (n=9) or placebo (n=11) therapy Post-Gad.STIR T1 %-change Braun J et al., Arthritis Rheum 2003 April; 48: 1126

  10. Assessments in Spondyloarthritides • 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

  11. ASAS working group criteria for improvement and remission in AS (JJ Anderson, D van der Heijde, DT Felson, M Dougados. A&R 2001;) 20% Improvement: • 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: • Patient global • Pain • Function (BASFI) • Inflammation (last 2 questions of the BASDAI on morning stiffness) and • absence of deterioration of at least 20% and absolute change of • at least 10 on a 0-100 scale in the potential remaining domain Partial remission: • a value below 20 on a 0-100 scale in each of the 4 domains

  12. Improvement criteria for treatment with biologics in AS – a data driven analysis based on the RCT with Infliximab (n=69) Domains: 1. Metrology (BASMI) 4. Patients global (VAS) 2. CRP 5. Function (BASFI) 3. Pain on VAS 6. Morning stiffness/BASDAI

  13. Development 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

  14. ASAS members participation First questionnaire Full ASAS members participation : 61% (36/59) Second questionnaire Full ASAS members participation : 56% (33/59)

  15. Question 1 ASAS members estimation Percentage of patients potentially candidate for biologics

  16. Question 3 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%

  17. Question 1 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 2

  18. Topic 1 When can biologics initiation can be considered, in daily practice?

  19. Question 4 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)

  20. Question 5 (1/3) Are the criteria selected by the Delphi exercise for axial involvement acceptable for you? Yes : 75%

  21. 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) 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

  22. Question 5 (3/3) Disagreement was because : 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

  23. Question 7 (1/3) Are the criteria selected by the Delphi exercise for enthesitis presentation acceptable for you? Yes : 69%

  24. Question 8 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%

  25. Question 4 Concerning the initiation of biologics in AS, which of the following do you feel should be considered?

  26. Question 10 (1/3) Concerning the objective assessments, what is your opinion concerning the definition of an active disease?

  27. Question 12 (1/2) Variables to collect in order to evaluate biologics efficacy Acute phase reactants Function Spinal mobility

  28. International ASAS consensus statement for the clinical use of anti-TNFa-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

  29. List of ASAS members/ participants/questionnaire co-workers • 1.Adebajo A O, UK • 2.Amor B, France • 3.Boers M, NL • 4.Boonen A, NL • 5.Bosch van den, F, Belgium • 6.Brandt J, Germany • 7.Braun J, Germany * • 8.Burgos Vargas R, Mexico • 9.Calin A, UK • 10.Clegg D, USA • 11.Collantes Estevez E, Spain • 12.Darmawan J, Indonesia • 13.Davis J, USA * • 14.Dougados M, France * • 15.Dijkmans B A C, NL • 16.Edmonds J, Australia • 17.Emery P, UK • 18.Feltelius N, Sweden • 19.Géher P, Hungary • 20.Guillemin F, France 21.Heijde van der D, NL* 22.Horst v.d.-Bruinsma I, NL 23.Khan MA, USA 24.Kirazli J, Turkey 25.Kuipers J, Germany 26.Landewé R, NL 27.Leirisalo-Repo M, Finland 28.Linden v. d. S, NL * 29.Linssen A., NL 30.Listing J, Germany 31.Maetzel A, Canada 32.Maksymowych W, Canada 33.Mielants H, Belgium 34.Olivieri I., Italy 35.Peloso P, USA 36.Pham T, France 37.Reveille J, USA 38.Riel van, NL 39.Rudwaleit M, Germany 40.Russell A S, Canada 41.Salvarani, C., Italy 42.Sieper J., Germany * 43.Stone M A, Canada 44.Sturrock R, UK 45.Yu, D, USA 46.Zeidler H, Germany * Steering Committee Members of ASAS

  30. Why are guidelines for the use of anti-TNFa treatment in AS needed? • 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

  31. Methodology employed to develop the guidelines • Review of the current literature • Expert opinion • Delphi exercise • Consensus meeting of the international assessment in AS (ASAS) working group

  32. Questions concerning the use of anti-TNFa therapy in AS • 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 ?

  33. What patients are candidates to consider for anti-TNFa therapy? • Persistence of active disease • Threat of severe disease (damage) • Likelihood of response to therapy

  34. International consensus on anti-TNFa therapy in ankylosing spondylitis • Initiation • Monitoring • Discontinuation • Diagnosis • Disease activity • Failure of conventional Treatment • Absence of contraindications • Monitoring • Discontinuation ASAS Meeting in Berlin January 2003 Braun J et al. Ann Rheum Dis 9/2003

  35. 1. Diagnosis of 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

  36. 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

  37. 2. Disease activity before anti-TNFa therapy 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.

  38. 3. Treatment failure before anti-TNFa therapy • Different for patients with predominantly • Axial disease • Peripheral disease • Entheseal disease

  39. 3. Treatment failure before anti-TNFa 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.

  40. 3. Treatment failure before anti-TNFa therapy • 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.

  41. 3. Treatment failure before anti-TNFa therapy • Patients with symptomatic enthesitis must have had an adequate therapeutic trial of at least two local steroid injections unless contraindicated.

  42. 4. Contraindications for anti-TNFa therapy • 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

  43. 4. Contraindications for anti-TNFa 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)

  44. 5. Monitoring of anti-TNFa therapy • BASDAI • ASAS core set

  45. ASAS core set of assessments for daily practice • 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

  46. 6. Discontinuation of anti-TNFa therapy • < 50% relative change or absolute change of 20 mm of BASDAI and Expert Opinion : Continuation yes/no • after 6 to 12 weeks of treatment

  47. Further development • 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)

  48. Personal proposal: link PsA working group to ASAS Future: Assessments in SpA working group ?

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