1 / 74

Dr. X. Baraliakos Rheumazentrum Ruhrgebiet, Herne Ruhr-University Bochum Germany

Anti-TNF therapy in ankylosing spondylitis - Clinical and structural outcomes -. Dr. X. Baraliakos Rheumazentrum Ruhrgebiet, Herne Ruhr-University Bochum Germany. Ankylosing spondylitis: a chronic inflammatory rheumatic disease leading to high clinical impairment. 24 years.

ernie
Download Presentation

Dr. X. Baraliakos Rheumazentrum Ruhrgebiet, Herne Ruhr-University Bochum Germany

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Anti-TNF therapy in ankylosing spondylitis - Clinical and structural outcomes - Dr. X. Baraliakos Rheumazentrum Ruhrgebiet, Herne Ruhr-University Bochum Germany

  2. Ankylosing spondylitis: a chronic inflammatory rheumatic disease leading to high clinical impairment 24 years • Involvement of axial skeleton, entheses, perhipheral joints and other organs (e.g. eyes) • Main clinical symptom: inflammatory back pain • 1/3 of patients with severe clinical course • High prevalence (0.5%) • Strong association with HLA-B27 • Late delay of diagnosis (5-7 years) • Decreased QoL • High risk of sick leave • Increased direct / indirect costs AS 49 years Braun J, Sieper J. Lancet 2007

  3. InflammationdrivenbyTNFa in AS Detection of TNF α mRNA in thebonemarrow of inflammedsacroiliacjoints • mRNABraun J et al.Arthritis Rheum 1995; 38: 499 • proteinBraun J et al.Ann Rheum Dis 2000; 59S: 85 • bone marrowFrancois R et al.Ann Rheum Dis 2005

  4. NSAIDs areefficaciousin AS within 24 hours ! Amor B, et al. Rev Rheum Engl Ed 1995;62:10–5 Van der Heijde, et al. Arthritis Rheum 2005;52:1205–15

  5. Many AS patients are refractory to NSAIDs % Patients 42% 29% Clinical trials*n = 462 OASIS†n = 209 *Patients after 6 weeks of treatment with an active NSAID †Epidemiological study = systematic recruitment of consecutive patients in daily practice

  6. Sulfasalazine in early SpA Disease activity in SpA patients with inflammatory back pain, with vs. without peripheral arthritis BASDAI BASDAI IBP+, Peripheral arthritis - IBP+, Peripheral arthritis + IBP+, Peripheral arthritis - p = 0.027 p = 0.3 IBP+, Peripheral arthritis + at 6 months at baseline at 6 months at baseline Placebo (n = 118) Sulfasalazine (n = 112) Braun J, Baraliakos X et al. Ann Rheum Dis 2006 Sep;65(9):1147-53

  7. ASAS/EULAR recommendations for the management of AS Education, exercise, physical therapy, rehabilitation, patient associations, self help groups NSAIDs Ana l ges i cs Peripheral disease Axial disease Su r ge r y Sulfasalazine Local corticosteroids TNF blockers Zochling J et al. Ann Rheum Dis 2006 Apr;65(4):442-52

  8. TNF Antagonists – a mile stone in the history of treatment of the (spondylo)arthritides Physikalische und pharmakologische Eigenschaften

  9. Anti-TNF therapy in AS- clinicaldata Short-term data: Baseline - 6 months

  10. The pilot study: infliximab in AS– open continuation phase Infusions given according to disease activity (BASDAI) Brandt J et al. Arthritis Rheum 2000; 43(6):1346

  11. Anti-TNF therapy in AS: Most patients achieve at least a 50% reduction of disease activity 2 6 12 weeks Braun J et al. Lancet 2002; 359:1187-93

  12. Significant improvement of function and spinal mobility Braun J et al. Lancet 2002; 359:1187-93

  13. Early experiences with etanercept in AS Improvement of disease activity (BASDAI) n=30 ETN treatment in ETN group ETN treatment in Placebo group p = 0.003 Brandt J et al. Arthritis Rheum 2003; 48: 1667

  14. Approval of etanercept for AS ASAS 20 Response Weeks 12 and 24 *P < 0.0001 Patients Responding (%) Davis JC, Arthritis Rheum 2003; 8: 3230-3236

  15. Etanercept treatment in ASReduction of acute phase reactants Etanercept 2 x 25 mg/Wk (n=138) Placebo (n=139) BSG (mm/h) Mittlere Änderung gegenüber dem Ausgangswert in % Mittlere Änderung gegenüber dem Ausgangswert in % CRP (mg/dl) † p < 0,0001 † p < 0,0001 † † † † † † Week 2 Month 6 Month 3 Week 2 Month 6 Month 3 Davis JC, Arthritis Rheum 2003; 8: 3230-3236

  16. Efficacy of Adalimumab in patients with AS – The ATLAS Trial – *** *** *** *** *** *** Week 24 Week 12 van der Heijde D, Arthritis Rheum, 2006. 54(7): 2136-2146 ***Statistically significant at p<0.001 level (ANCOVA)

  17. Adalimumab1 Etanercept2 * Pbon=107 Ada 40 mg eown=208 Pbo n=139 Etan 25 mg BIWn=138 Infliximab Golimumab * * * Pbon=78 Ifx 5 mg/kgn=201 Pbon=75 Glm 50 mgn=130 Glm 100 mgn=138 ASAS 40 Response at Week 24 in Trials of Biologics for AS 1van der Heijde D, et al. Arthritis Rheum. 2006;54:2136-2146; 2Davis JC, et al. Arthritis Rheum. 2003;48:3230-3236; 3van der Heijde D, et al. Arthritis Rheum. 2005;52:582-591. * P <.001 vs placebo

  18. Anti-TNF therapy in AS- clinical data Long-term follow-up: 6 months – 8 years

  19. Patients with BASDAI 50% Response after 3 years of infliximab treatment Placebo-controlled phase Open phase Braun J, Rheumatology 2005. 44(5):670-6

  20. Continuous improvement of spinal mobility and function over 3 years Placebo-controlled phase Placebo controlled phase Open phase Open Phase Mean BASMI Mean BASFI Braun J, Rheumatology 2005. 44(5):670-6

  21. Anti-TNFα therapy in patients with ASResults after 8 years Infliximab Baraliakos X, EULAR 2009, Copenhagen

  22. Anti-TNFα therapy in patients with ASResults after 6 years Etanercept Baraliakos X, EULAR 2009, Copenhagen

  23. Anti-TNFα therapy in patients with ASResults after 6 years Etanercept 35.1% 33.3% Baraliakos X, EULAR 2009, Copenhagen

  24. Efficacy of Adalimumab in patientswith AS – long-termdatafromthe ATLAS Trial 2 years 3 years vd Heijde D et al, Ann Rheum Dis2008 vd. Heijde D, Arthritis Res Ther 2009, 11:R124

  25. Golimumab - ASAS Partial Remission after 104 weeks Placebo/ Golimumab 50mg (n = 78) Golimumab 50 mg(n = 138) Golimumab 100 mg(n = 140) GO-RAISE Anteil Patienten (%) Braun J. et al. ACR 2009, Abstract 1259 Braun J et al, ACR 2009, Abstract 1259

  26. Placebo/ Golimumab 50mg (n = 78) Golimumab 50 mg(n = 138) Golimumab 100 mg(n = 140) GO-RAISE Golimumab – ASAS 40 Response after 104 weeks Anteil Patienten (%) Braun J. et al. ACR 2009, Abstract 1259 Braun J et al, ACR 2009, Abstract 1259

  27. Discontinuationof anti-TNF- treatment Anti-TNF therapy in AS- clinical data

  28. Design of studies • Withdrawal of biologic in all patients • Regular visits to assess clinical relapse (BASDAI > 4 and PhysGA > 4) • Retreatment with same dosis • Assessment of clinical parameters ETN: Brandt J et al. Arthritis Rheum 2003; 48: 1667 Baraliakos X et al, Arthritis Rheum 2005 (53): 856-863 INF: Baraliakos X et al, Arthritis Res Ther 2005. 7(3): R439-44

  29. Clinically successful readministration of infliximab after withdrawal in all patients without infusion reactions Infliximab withdrawal Baraliakos X, Arthritis Res Ther 2005. 7(3): R439-44

  30. Clinically successful readministration of infliximab after withdrawal in all patients without infusion reactions Infliximab withdrawal Baraliakos X, Arthritis Res Ther 2005. 7(3): R439-44

  31. Clinically successful readministration of infliximab after withdrawal in all patients without infusion reactions Infliximab withdrawal Baraliakos X, Arthritis Res Ther 2005. 7(3): R439-44

  32. BASDAI 50%, ASAS 40% response and partial remission after infliximab readministration Infliximab withdrawal after infliximab readministration Baraliakos X, Arthritis Res Ther 2005. 7(3): R439-44

  33. Duration of response after withdrawal mean time to relapse: 17.5 ± 7.9 weeks (range 7 – 45 wk, median 15 wk)

  34. Correlation between disease activity (BASDAI) and response to withdrawal 100% 100% (p=0.039) (p=0.039) 80% 80% 60% 60% 40% 40% 20% 20% 0% 0% 0 0 6 6 12 12 18 18 24 24 30 30 36 36 42 42 48 48 time to relapse (weeks) time to relapse (weeks) pts. with BASDAI < 3 pts. with BASDAI < 3 pts. with BASDAI >= 3 pts. with BASDAI >= 3 100% (p=0.039) 80% 60% 40% 20% 0% 0 6 12 18 24 30 36 42 48 Kaplan-Meier Analysis Log rank test pts. with BASDAI < 3 pts. with BASDAI >= 3 Baraliakos X, Arthritis Res Ther 2005. 7(3): R439-44

  35. Response to retreatment • Clear improvement of signs and symptoms • Disease status similar to before withdrawal • No adverse event, no other safety concern after resumption of etanercept and infliximab therapy ETN: Brandt J et al. Rheumatology (Oxford). 2005 Mar;44(3):342-8. Baraliakos X et al, Arthritis Rheum 2005 (53): 856-863 INF: Baraliakos X et al, Arthritis Res Ther 2005. 7(3): R439-44

  36. Anti-TNF therapy in AS- clinicaldata Additional data

  37. Anti-TNFα in AS Patientswithtotal spinal ankylosis– Data fromthe ATLAS Trial – • Total spinal ankylosis (TSA) represents end-stage fusion of the spine in patients (pts) with ankylosing spondylitis (AS) • It is not uncommon for pts who already have TSA to still have symptoms of active disease. vd Heijde et al, Ann Rheum Dis 2008;67:1218-1221

  38. Anti-TNFα in AS Patientswithtotal spinal ankylosis– Data fromthe ATLAS Trial – • Total spinal ankylosis (TSA) represents end-stage fusion of the spine in patients (pts) with ankylosing spondylitis (AS) • It is not uncommon for pts who already have TSA to still have symptoms of active disease. vd Heijde et al, Ann Rheum Dis 2008;67:1218-1221

  39. Etanercept25mg/week- effectivein somepatientswithactive AS Berthelot J, Joint Bone Spine 74 (2007); 144-147 n = 21 n = 20

  40. Improvement of key disease parameters by 3 mg/kg Infliximab Maksymowych WP et al., J Rheumatol 2002; 29:959-65

  41. Infliximab every 6 w. vs on demand therapy- response after 54 weeks:continuous treatment is superior % 75% 46% 27% 7% Breban M et al, Arthritis Rheum 2008 (58):88-97

  42. Addition of MTX to infliximab in patients with ankylosing spondylitis – response after 54 weeks:almost no difference % 10% 40% 5% 51% Breban M et al, Arthritis Rheum 2008 (58):88-97

  43. Evidence for different types of response to anti-TNF treatment in AS Three groups of patients according to level and degree of response after 5 years of infliximab treatment: Group A: remission at most time points (> 20/25 visits) Group B: low disease activity (BASDAI < 3) (> 20/25 visits) Group C: limited improvement, not fulfilling ASAS 20 at all time points, BASDAI > 4 at some time points Differences between groups: mean age (< / > 40 yrs, mean disease duration (< / > 10 yrs, mean BASFI at BL < / > 5) Braun J, Baraliakos X et al, in press

  44. Switching anti-TNF therapy in SpA infliximab toetanercept • patients with SpA n = 15 • 11 female, 4 male, mean age 43 • AS (n = 7) • uSpA (n = 6) • PsA (n = 2) • predominat axial involvement (n=13) • mean time of treatment with infliximab 11 months • inadequate response or loss of response (n=11) • side effects (n=5) • after 9 months 9/13 patients responded Delaunay C et al. J Rheumatol 2005

  45. Which AS patientsshouldbetreatedwith TNF-blockers?

  46. ASAS-Consensus Statement TNF-Blockers in ankylosing spondylitis Diagnosis of AS 2 NSAIDs within3 m. Non-respondersto NSAIDs Increaseddiseaseactivity BASDAI > 4 + Positive expert‘sopinion Braun J, Ann Rheum Dis 2003, 62: 817-24 Braun J, Ann Rheum Dis 2006, 65: 201-8

  47. Positive expert‘sopinion:based on objectivesigns of inflammation • Clinical examination/Patient‘sclinicalhistory • Pos. CRP/ESR • Pos. MRI • Radiographicprogression

  48. ASAS-Consensus Statement TNF-Blockers in ankylosing spondylitis Start of therapywith TNF-blockers Improvement after 3 months BASDAI-Improvement> 50% or BASDAI-Improvement> 2 (0-10) + Pos. expert´sopition Braun J, Ann Rheum Dis 2003, 62: 817-24 Braun J, Ann Rheum Dis 2006, 65: 201-8

  49. Safetydata– Infliximab – Braun J, Baraliakos X et al, Ann Rheum Dis. 2008 March 1, 2008;67(3):340-5

  50. Anti-TNF therapy in AS Imaging

More Related