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Defining Suboptimal Response to MS Treatment: MRI Outcome

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Defining Suboptimal Response to MS Treatment: MRI Outcome

  1. 1. Tony Traboulsee, MD (Neurology) University of British Columbia CMSC June 5th, 2004 Toronto, Ontario Defining suboptimal response to MS treatment: MRI outcome
  2. 2. Disclosure <ul><li>I have received honoraria from the Consortium of MS Centers and from all the major pharmaceutical companies currently involved in MS clinical trials of DMTs. </li></ul>
  3. 3. <ul><li>1984 </li></ul><ul><li>MRI detects clinically silent lesions. </li></ul><ul><li>Its role in monitoring individual patients is unknown. </li></ul>0.15 Tesla MRI, UBC
  4. 4. What is the value of MRI in monitoring MS patients? <ul><li>1. Does MRI predict if a patient will have clinical relapses? </li></ul><ul><li>Does MRI predict clinical disability? </li></ul><ul><li>Does MRI predict treatment response? </li></ul><ul><li>Is the clinical MRI data reliable? </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  5. 5. What is the value of MRI in monitoring MS patients? <ul><li>1. Does MRI predict if a patient will have clinical relapses? </li></ul><ul><li>Does MRI predict clinical disability? </li></ul><ul><li>Does MRI predict treatment response? </li></ul><ul><li>Is the clinical MRI data reliable? </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  6. 6. Bashir analog model for assessing the effectiveness of therapeutic strategies Reproduced without permission from International Journal of MS Care 2002 (suppl):1-7
  7. 7. Freedman analog model for assessing the effectiveness of MS therapies. Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
  8. 8. Why do any test in medicine? <ul><li>To monitor the disease course. </li></ul><ul><li>To predict clinical outcome. </li></ul><ul><li>To modify therapy. </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  9. 9. Freedman analog model for assessing the effectiveness of MS therapies. Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
  10. 10. Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
  11. 11. What is the value of MRI in monitoring MS patients? Dr. T. Traboulsee, UBC MS/MRI Research Group
  12. 12. Does a single MRI Predict Relapses? <ul><li>MRI abnormalities in CIS predict CDMS (Brex 14 year natural history cohort NEJM 2003) </li></ul><ul><li>Gad activity predicts higher rate of conversion from CIS to CDMS (CHAMPS) </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  13. 13. Does a single MRI Predict Relapses? <ul><li>An initial MRI with no gad lesions would predict 1.3 relapses in the next year. </li></ul><ul><li>An initial MRI with 10 gad lesions would predict 1.6 relapses in the next year. </li></ul><ul><li>Kappos Meta Analysis of 307 patients, Lancet 1999 </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  14. 14. Do Serial MRI Predict Relapses? <ul><li>PPV 0.2 when using monthly gad activity on MRI predicting relapse at 6 months (Koziol AJNR 2002) </li></ul><ul><li>R = 0.25 for monthly MRI gad activity correlating with relapses (Rovaris AJNR 2003) </li></ul><ul><li>The relative risk of having a relapse at 1 or 2 years was slightly increased ( RR 1.13) by the presence of gad lesions with 6 monthly scans (Kappos Lancet 1999) </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  15. 15. What is the value of MRI in monitoring MS patients? <ul><li>1. Does MRI predict if a patient will have clinical relapses? </li></ul><ul><li>Does MRI predict clinical disability? </li></ul><ul><li>Does MRI predict treatment response? </li></ul><ul><li>Is the clinical MRI data reliable? </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  16. 16. Does a single MRI Predict Disability? <ul><li>CIS patients with larger number and volume of T2 lesions tend to have greater disability at 14 years (Brex NEJM 2002) </li></ul><ul><li>There was no relationship between gad enhancing lesions at baseline and EDSS at 2 years. ( Kappos Meta Analysis, Lancet 1999) </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  17. 17. Do serial MRI Predict Disability? <ul><li>New T2 activity weakly correlated with relapses (r=0.2) but not with disability at 5 years . </li></ul><ul><li>Change in BOD weakly correlated with relapses (r=0.2) and with EDSS (r=0.3) </li></ul>Paty, IFNB RRMS study, 115 Placebo patients followed with annual MRI for 5 years
  18. 18. Do serial MRI Predict Disability? <ul><li>New T2 activity weakly predicts disability at 2-3 years of follow-up (r=0.13, p=0.02). </li></ul>Filippi et al, pooled data of 281 MS patients, Neurology 1995
  19. 19. Do serial MRI Predict Disability? <ul><li>The most active patients on MRI have a worse prognosis than the less active ones. </li></ul><ul><li>However, there is so much overlap between groups that one cannot yet predict prognosis for individual patients . </li></ul><ul><li>Paty, AAN 1992 </li></ul>
  20. 20. What is the value of MRI in monitoring MS patients? <ul><li>1. Does MRI predict if a patient will have clinical relapses? </li></ul><ul><li>Does MRI predict clinical disability? </li></ul><ul><li>Does MRI predict treatment response? </li></ul><ul><li>Is the clinical MRI data reliable? </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  21. 21. Does MRI predict Treatment Success? Observations from RRMS: <ul><li>Studies have shown up to a 90% suppression of new gadolinium enhancement lesions. </li></ul><ul><li>These studies also showed no net accumulation of total T2 lesion load. </li></ul><ul><li>However, the clinical impact on relapses is only modest (33% reduction), and the long term impact on clinical disability remains controversial. </li></ul>
  22. 22. Change from Baseline in MRI Area Pivotal IFN beta 1b RRMS study T2 BOD is suppressed compared to placebo
  23. 23. IFN Beta-1a: % Change of BOD from Baseline Population Distribution 0 10 20 30 -40 -20 0 20 40 60 80 100 120 140 160 180 200 % of patients % change in BOD from baseline Placebo Rebif 44 TIW GOOD MRI Outcome POOR MRI Outcome
  24. 24. Does MRI predict Treatment Success? Observations from SPMS: <ul><li>Studies have shown similar suppression of new inflammatory MRI activity and on T2 BOD as seen in RRMS. </li></ul><ul><li>However, there is no consistent clinical impact on disability. </li></ul>
  25. 25. What is the value of MRI in monitoring MS patients? <ul><li>1. Does MRI predict if a patient will have clinical relapses? </li></ul><ul><li>Does MRI predict clinical disability? </li></ul><ul><li>Does MRI predict treatment response? </li></ul><ul><li>Is the clinical MRI data reliable? </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  26. 26. CMSC MRI Protocol <ul><li>If a follow-up MRI is to be done, it should be performed by the standardized MRI protocol. </li></ul>Dr. A. Traboulsee and the CMSC work group
  27. 27. Total Lesion Frequency and EDSS 12 24 36 48 Months Number of Gd enhancing lesions 10 8 6 4 2 5 4 3 2 EDSS Kindly provided by Joe Frank, NIH
  28. 28. Why do any test in medicine? <ul><li>To monitor the disease course. </li></ul><ul><li>To predict clinical outcome. </li></ul><ul><li>To modify therapy. </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  29. 29. How can this be applied to individual patients? <ul><li>There is so much overlap between groups that one cannot yet predict prognosis for individual patients. </li></ul><ul><li>Paty, AAN 1992 </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group
  30. 30. Conclusion <ul><li>Treat the patient, </li></ul><ul><li>not the test. </li></ul>Dr. T. Traboulsee, UBC MS/MRI Research Group.

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